PROTOCOL PD0049 - ClinicalTrials.govUCB Biopharma SPRL Allée de la Recherche 60 1070 Brussels...
39
UCB 16 Dec 2016 Clinical Study Protocol Rotigotine transdermal system PD0049 Confidential Page 1 of 38 PROTOCOL PD0049 A MULTICENTER, OPEN-LABEL, TWO-ARM STUDY TO EVALUATE THE IMPACT OF USING WEARABLE DEVICES IN ADDITION TO STANDARD CLINICAL PRACTICE ON PARKINSON’S SUBJECT SYMPTOMS MANAGEMENT PHASE 4 Sponsor: UCB Biopharma SPRL Allée de la Recherche 60 1070 Brussels BELGIUM Protocol/Amendment number Date Final protocol 16 Dec 2016 Confidential Material Confidential This document is the property of UCB and may not – in full or in part – be passed on, reproduced, published, or otherwise used without the express permission of UCB. REDACTED COPY erch erch russel russel ELGI ELGI t cannot be used to support any marketing authorization application and any extensions or variations thereof. 60 60 ls ls UM UM ol/Am ol/Am any protoco protoco port sup This document ca t ca
Transcript of PROTOCOL PD0049 - ClinicalTrials.govUCB Biopharma SPRL Allée de la Recherche 60 1070 Brussels...
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 1 of 38
PROTOCOL PD0049
A MULTICENTER, OPEN-LABEL, TWO-ARM STUDY TO EVALUATE THE IMPACT OF USING WEARABLE DEVICES IN
ADDITION TO STANDARD CLINICAL PRACTICE ONPARKINSON’S SUBJECT SYMPTOMS MANAGEMENT
PHASE 4
Sponsor:
UCB Biopharma SPRL
Allée de la Recherche 60
1070 Brussels
BELGIUM
Protocol/Amendment number Date
Final protocol 16 Dec 2016
Confidential Material
Confidential
This document is the property of UCB and may not – in full or in part – be passed on, reproduced, published, or otherwise used without the express permission of UCB.
REDACTED COPY Allée de la Recherche 60
REDACTED COPY Allée de la Recherche 60
1070 Brussels
REDACTED COPY
1070 Brussels
BELGIUM
REDACTED COPY
BELGIUM
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Allée de la Recherche 60
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Allée de la Recherche 60
1070 Brussels
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
1070 Brussels
BELGIUM
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
BELGIUM
Protocol/Amendment number
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Protocol/Amendment number
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Final protocol
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Final protocol
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 2 of 38
STUDY CONTACT INFORMATION
Sponsor
UCB Biopharma SPRL
Allée de la Recherche 60
1070 Brussels
BELGIUM
Sponsor Study Physician
Name: , MD
Address: UCB Biosciences, Inc.
8010 Arco Corporate Drive
Raleigh, NC 27617
UNITED STATES OF AMERICA
Phone:
Fax:
Clinical Project Manager
Name:
Address: UCB Biosciences, Inc.
8010 Arco Corporate Drive
Raleigh, NC 27617
UNITED STATES OF AMERICA
Phone:
Fax:
REDACTED COPY
REDACTED COPY
REDACTED COPY
REDACTED COPY
BiosciencesREDACTED C
OPY
Biosciences
8010 Arco Corporate DriveREDACTED C
OPY
8010 Arco Corporate DriveREDACTED C
OPY
REDACTED COPY
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Biosciences
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Biosciences, I
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
, Inc.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
nc.
8010 Arco Corporate Drive
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
8010 Arco Corporate Drive
Raleigh, NC
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Raleigh, NC 27617
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
27617
UNITED STATES OF AMERI
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
UNITED STATES OF AMERI
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 3 of 38
Clinical Trial Biostatistician
Name: , MSc
Address: UCB Biosciences GmbH
Alfred-Nobel-Strasse 10
40789 Monheim
GERMANY
Phone:
Fax:
Clinical Monitoring Contract Research Organization
Name: PAREXEL International
Address: 1 Federal Street
Billerica, MA 01821
UNITED STATES OF AMERICA
Phone: +1 978 313 3900
Fax: +1 781 768 5512
Device Manufacturer
Name: Great Lakes Neuro Technologies, Inc. (GLNT)
Address: 10055 Sweet Valley Drive
Valley View, OH 44125
UNITED STATES OF AMERICA
Phone: +1 855 456 3876
Fax: +1 216 361 5420
Device Manufacturer/Complaint Reporting
Name: Great Lakes Neuro Technologies/
Phone: Office: (9:00am – 5:00pm EST)
Mobile (after business hours)
email:
REDACTED COPY
REDACTED COPY
REDACTED COPY
Great Lakes Neuro TechnologiesREDACTED C
OPY
Great Lakes Neuro TechnologiesREDACTED C
OPY
REDACTED COPY
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Great Lakes Neuro Technologies
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Great Lakes Neuro Technologies
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
10055 Sweet Valley Drive
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
10055 Sweet Valley Drive
Valley View, OH 44125
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Valley View, OH 44125
UNITED STATES OF AMERICA
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
UNITED STATES OF AMERICA
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
+1 855 456 3876
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
+1 855 456 3876
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
+1 216 361 5420
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
+1 216 361 5420
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Device Manufacturer/Complaint Reporting
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Device Manufacturer/Complaint Reporting
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Phone:
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Phone:
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 4 of 38
SERIOUS ADVERSE EVENT REPORTING
Serious adverse event reporting (24h)
Fax USA: +1 800 880 6949or +1 866 890 3175
Email Global: [email protected] (for interventional clinical studies)
REDACTED COPY
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 5 of 38
TABLE OF CONTENTS
LIST OF ABBREVIATIONS.................................................................................................... 8
1 SUMMARY..................................................................................................................... 10
2 INTRODUCTION ........................................................................................................... 11
3 STUDY OBJECTIVES.................................................................................................... 12
3.1 Primary objectives ........................................................................................................... 12
3.2 Other objectives ............................................................................................................... 12
4 STUDY VARIABLES..................................................................................................... 13
4.1 Efficacy variables............................................................................................................. 13
4.1.1 Primary efficacy variables ................................................................................... 13
4.1.2 Other efficacy variables ....................................................................................... 13
4.2 Safety variables ................................................................................................................ 14
5 STUDY DESIGN............................................................................................................. 14
5.1 Study description ............................................................................................................. 14
5.1.1 Study duration per subject ................................................................................... 14
5.1.2 Planned number of subjects and sites .................................................................. 14
5.1.3 Anticipated regions and countries ....................................................................... 15
5.2 Schedule of study assessments......................................................................................... 15
5.3 Rationale for study design and selection of dose............................................................. 18
6 SELECTION AND WITHDRAWAL OF SUBJECTS................................................... 18
6.1 Inclusion criteria .............................................................................................................. 18
6.2 Exclusion criteria ............................................................................................................. 18
6.3 Withdrawal criteria .......................................................................................................... 19
7 MEDICINAL PRODUCT AND DEVICE ...................................................................... 19
7.1 Description of medicinal product..................................................................................... 19
7.2 Devices............................................................................................................................. 19
7.2.1 Description of devices ......................................................................................... 20
7.2.2 Packaging and labeling of the Kinesia devices.................................................... 21
7.2.3 Storage requirements ........................................................................................... 21
7.2.4 Device accountability .......................................................................................... 21
7.3 Concomitant medications/treatments............................................................................... 21
7.3.1 Rescue medication ............................................................................................... 21
7.4 Blinding............................................................................................................................ 21
7.5 Randomization and numbering of subjects...................................................................... 21
8 STUDY PROCEDURES BY VISIT ............................................................................... 22
8.1 Visit 1 /Screening............................................................................................................ 22
8.2 Week 1 ............................................................................................................................. 22
8.3 Weeks 2, 3, and 4 ............................................................................................................. 23
REDACTED COPY ................................
REDACTED COPY ................................
................................
REDACTED COPY
................................
................................
REDACTED COPY
................................
y design and selection of dose
REDACTED COPY
y design and selection of dose
AWAL
REDACTED COPY
AWAL OF SUBJECTS
REDACTED COPY
OF SUBJECTS
................................REDACTED COPY
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
............... 12
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
............... 12
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
..................................... 13
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
..... 13
............. 13
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
............. 13
................... 13
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................... 13
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
....................................................... 13
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
....................... 13
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
y design and selection of dose
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y design and selection of dose
OF SUBJECTS
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
OF SUBJECTS
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
NAL PRODUCT AN
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
NAL PRODUCT AND DEVI
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
D DEVI
Description of medicinal product
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Description of medicinal product
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
Description of devices
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Description of devices
Packaging and labeling of the Kinesia devices
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Packaging and labeling of the Kinesia devices
Storage requirements
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Storage requirements
Device accountability
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Device accountability
7.3 Concomitant medications/treatments................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
7.3 Concomitant medications/treatments................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
7.3.1 Rescue medication ................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
7.3.1 Rescue medication ................................
7.4 Blinding................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
7.4 Blinding................................
7.5
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
7.5
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 6 of 38
8.4 Week 5 up to Week 12..................................................................................................... 23
8.5 Visit 2 (End of Study Visit) (Week 12 ±3 days).............................................................. 24
8.6 Early Withdrawal Visit .................................................................................................... 24
9 ASSESSMENT OF EFFICACY...................................................................................... 24
9.1 Inclusion criteria threshold related to tremor and/or bradykinesia .................................. 24
9.1.1 Unified Parkinson’s Disease Rating Scale .......................................................... 25
9.1.2 39-Item Parkinson’s Disease Questionnaire ........................................................ 25
10 ASSESSMENT OF SAFETY.......................................................................................... 25
10.1 Adverse events ................................................................................................................. 25
10.1.1 Definitions ........................................................................................................... 25
10.1.1.1 Adverse event ............................................................................................ 25
10.1.1.2 Serious adverse event ................................................................................ 25
10.1.1.3 Adverse events of special interest ............................................................. 26
10.1.2 Procedures for reporting and recording adverse events and other safety related information .......................................................................................................... 26
10.1.2.1 Description of adverse events.................................................................... 27
10.1.2.2 Rule for repetition of an adverse event...................................................... 27
10.1.2.3 Reporting of serious AEs (related or not to Neupro) ................................ 27
10.1.2.4 Device reporting ........................................................................................ 27
10.1.3 Follow up of adverse events ................................................................................ 27
10.1.4 Pregnancy and breastfeeding ............................................................................... 28
10.1.5 Overdose of medicinal product............................................................................ 28
10.2 Laboratory measurements ................................................................................................ 28
10.3 Other safety measurements .............................................................................................. 28
10.3.1 Rate of discontinuation of treatment with Neupro .............................................. 28
11 STUDY MANAGEMENT AND ADMINISTRATION ................................................. 29
11.1 Adherence to protocol ...................................................................................................... 29
11.2 Monitoring ....................................................................................................................... 29
11.2.1 Definition of source data ..................................................................................... 29
11.2.2 Source data verification ....................................................................................... 30
11.3 Data handling ................................................................................................................... 30
11.3.1 Case Report form completion.............................................................................. 30
11.3.2 Database entry and reconciliation........................................................................ 30
11.3.3 Subject Screening and Enrollment log/Subject Identification Code list.............. 30
11.4 Termination of the study.................................................................................................. 30
11.5 Archiving and data retention............................................................................................ 31
11.6 Audit and inspection ........................................................................................................ 31
11.7 Good Clinical Practice ..................................................................................................... 31
REDACTED COPY Rule for repetition of an adverse event
REDACTED COPY Rule for repetition of an adverse event
10.1.2.3 Reporting of serious AEs (related or not to Neupro) ................................ 27
REDACTED COPY
10.1.2.3 Reporting of serious AEs (related or not to Neupro) ................................ 27
................................
REDACTED COPY
................................
................................
REDACTED COPY
................................
and breastfeeding
REDACTED COPY
and breastfeeding
Overdose of medicinal productREDACTED COPY
Overdose of medicinal product
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
........................ 25
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
........................ 25
.......................... 25
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
.......................... 25
................. 25
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................. 25
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
........................................... 25
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
........... 25
............................ 25
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
............................ 25
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
10.1.1.3 Adverse events of special interest ................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
10.1.1.3 Adverse events of special interest ............................................................. 26
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
............................. 26
Procedures for reporting and recording adverse events and other safet
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Procedures for reporting and recording adverse events and other safet................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
10.1.2.1 Description of adverse events................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
10.1.2.1 Description of adverse events................................
Rule for repetition of an adverse event
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Rule for repetition of an adverse event................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
10.1.2.3 Reporting of serious AEs (related or not to Neupro) ................................ 27
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
10.1.2.3 Reporting of serious AEs (related or not to Neupro) ................................ 27
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
Overdose of medicinal product
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Overdose of medicinal product................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
Rate of discontinuation of treatment with Neupro
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Rate of discontinuation of treatment with Neupro
11 STUDY MANAGEMENT AND
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
11 STUDY MANAGEMENT AND
Adherence to protocol
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Adherence to protocol
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
Definition of source data
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Definition of source data
11.2.2 Source data verification ................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
11.2.2 Source data verification ................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Data handling
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Data handling
11.3.1 Case Report form completion................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
11.3.1 Case Report form completion................................
11.3.2
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
11.3.2
11.3.3 Subject Screening and Enrollment log/Subject Identification Code list.............. 30
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
11.3.3 Subject Screening and Enrollment log/Subject Identification Code list.............. 30
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 7 of 38
12 STATISTICS ................................................................................................................... 31
12.1 Definition of analysis sets ................................................................................................ 32
12.2 General statistical considerations..................................................................................... 32
12.3 Planned efficacy analyses ................................................................................................ 32
12.3.1 Analysis of the efficacy variables........................................................................ 32
12.3.2 Other efficacy analyses........................................................................................ 33
12.4 Planned safety analyses.................................................................................................... 33
12.4.1 Safety analyses..................................................................................................... 33
12.5 Handling of protocol deviations....................................................................................... 33
12.6 Handling of dropouts or missing data .............................................................................. 33
12.7 Planned interim analysis and data monitoring ................................................................. 33
12.8 Determination of sample size........................................................................................... 34
13 ETHICS AND REGULATORY REQUIREMENTS...................................................... 34
13.1 Informed consent ............................................................................................................. 34
13.2 Subject identification cards.............................................................................................. 34
13.3 Institutional Review Boards............................................................................................. 34
13.4 Subject privacy................................................................................................................. 35
13.5 Protocol amendments....................................................................................................... 35
14 FINANCE, INSURANCE, AND PUBLICATION ......................................................... 35
15 REFERENCES ................................................................................................................ 36
16 DECLARATION AND SIGNATURE OF INVESTIGATOR ....................................... 37
17 SPONSOR DECLARATION .......................................................................................... 38
LIST OF TABLES
Table 5‒1: Schedule of study assessments......................................................................... 16
REDACTED COPY
................................
REDACTED COPY
................................
................................
REDACTED COPY
................................
REDACTED COPY
ND PUBLICATION
REDACTED COPY
ND PUBLICATION
................................
REDACTED COPY
................................................................
REDACTED COPY
................................
ATURE OF INVESTIREDACTED C
OPY
ATURE OF INVESTI
17 SPONSOR DECLARATION ................................REDACTED COPY
17 SPONSOR DECLARATION ................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
.... 33
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
.... 33
..... 33
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
..... 33
....................... 33
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
....................... 33
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
.............................................. 33
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
.............. 33
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
........................... 34
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
........................... 34
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ND PUBLICATION
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ND PUBLICATION
................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
................................
ATURE OF INVESTI
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ATURE OF INVESTI
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
17 SPONSOR DECLARATION ................................
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
17 SPONSOR DECLARATION ................................
Schedule of stud
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Schedule of study assessments
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y assessments
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 8 of 38
LIST OF ABBREVIATIONS
ADE adverse device event
AE adverse event
ANCOVA analysis of covariance
APP application, application software
ATC Anatomical Therapeutic Chemical
CDMS clinical data management system
CG Control Group
CI confidence interval
CRO contract research organization
DBS Deep Brain Stimulation
ECG electrocardiogram
eCRF electronic Case Report form
EG Experimental Group
ES Enrolled Set
FAS Full Analysis Set
FDA Food and Drug Administration
GLNT Great Lakes Neuro Technologies, Inc.
H0 null hypothesis
Ha alternative hypothesis
ICF Informed Consent form
ICH-GCP International Council for Harmonisation-Good Clinical Practice
IMP investigational medicinal product
IRB Institutional Review Board
ISO International Organization for Standardization
MedDRA Medical Dictionary for Regulatory Activities
n number
PDQ-39 39-Item Parkinson’s Disease Questionnaire
PPS Per-Protocol Set
PS Patient Safety
RLS restless leg syndrome
SAE serious adverse event
REDACTED COPY
Food and Drug Administration
REDACTED COPY
Food and Drug Administration
Great Lakes Neuro TechnologiesREDACTED COPY
Great Lakes Neuro Technologies
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Food and Drug Administration
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Food and Drug Administration
Great Lakes Neuro Technologies
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Great Lakes Neuro Technologies
pothesis
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
pothesis
alternative h
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
alternative hypothesis
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ypothesis
formed Consent form
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
formed Consent form
International Council for Harmonisation
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
International Council for Harmonisation
investigational medicinal product
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
investigational medicinal product
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
MedDRA
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
MedDRA
PDQ
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
PDQ-39
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
-39
PPS
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
PPS
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 9 of 38
SAP Statistical Analysis Plan
SD standard deviation
SOP Standard Operating Procedure
SS Safety Set
TEAE treatment-emergent adverse event
UPDRS Unified Parkinson’s Disease Rating Scale
REDACTED COPY
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 10 of 38
1 SUMMARY
PD0049 is a pilot study to investigate whether motor symptoms in subjects with Parkinson’s disease who start treatment with Neupro® can be improved by using wearable devices. Specifically, this study focuses on investigating how to optimize the evaluation of motor symptoms in subjects with Parkinson’s disease aiming at enabling Investigators to optimize subjects’ Neupro dosing regimens and ensure better patient outcomes in a timelier manner.
In this study, 2 Kinesia devices (Kinesia-ONE and Kinesia-360) will be employed to record specific motor symptoms. Approximately 40 subjects with Parkinson’s disease of any stage will be randomized (1:1 ratio) to either the Control Group or the Experimental Group. Specific motor tasks will be measured in all subjects with Kinesia-ONE on Day 1. In contrast to subjects randomized to the Control Group, subjects randomized to the Experimental Group will also use the Kinesia-360 device for home-based self-recording of their motor symptoms.
All subjects will start Neupro treatment at a dose of either rotigotine 2mg/24h or 4mg/24h (according to the disease stage of the subject), which will then be adjusted based on symptom assessment either via standard care alone (Control Group) or via a combination of standard care and evaluation of the recordings made available by the Kinesia wearable technologies(Experimental Group). The Neupro dosing regimen used in PD0049 follows standard of care, and is in line with the approved dosing regimen for rotigotine in the treatment of Parkinson’s disease (ie, up to 8mg/24h, depending on the stage of the disease).
PD0049 starts with in-clinic Screening activities, assessments (including recording of Baseline motor symptoms via Kinesia-One), and training in the use of Kinesia-360 devices (for subjects randomized to the Experimental Group only) on Day 1, followed by 3 days at home: During this period, subjects randomized to the Experimental Group will use the Kinesia-360 device to record their motor symptoms (on Days 2 and 3). Subjects allocated to the Control Group will start treatment with Neupro preferably on Day 1 (but no later than Day 4); subjects allocated to the Experimental group will start treatment with Neupro on Day 4. There are no required visits from Week 2 up to Week 12 (Visit 2). However, Investigators and subjects in the Experimental Group are encouraged to discuss by phone Kinesia-360 motor symptom reports and needs for any changes in Neupro dosing. Subjects of either group return to the clinic for final assessments and reporting of adverse events (AEs) and concomitant medications at Week 12. The individual duration of study participation may last up to 12 weeks.
A primary objective of PD0049 is to evaluate whether Parkinson’s disease motor symptoms in subjects starting Neupro can be improved by using feedback of motor symptom data from the Kinesia-360 wearable technology presented to subjects and Investigators in addition to standard clinical practice as compared with only standard clinical practice. A primary objective is to evaluate whether a clinician is more likely to determine a Neupro dosing regimen that improves a subject’s Parkinson’s disease motor symptoms when using motor symptom data collected with the Kinesia-360 wearable technology in addition to standard clinical practice as compared with only standard clinical practice. Another primary objective is to evaluate whether subjects with Parkinson’s disease are more likely to continue the usage of Neupro if Parkinson’s disease motor symptom data collected using the Kinesia wearable technology is used to provide the subjects with feedback on the status of their Parkinson’s disease motor symptoms and is used in addition to standard of care for titrating their Neupro dosing regimen. Other objectives include to evaluate
REDACTED COPY . The Neupro dosing regimen used in PD0049 follows standard of care,
REDACTED COPY . The Neupro dosing regimen used in PD0049 follows standard of care,
for rotigotine in the treatment of Parkinson’s
REDACTED COPY for rotigotine in the treatment of Parkinson’s
disease (ie, up to 8mg/24h, depending on the stage of the disease).
REDACTED COPY
disease (ie, up to 8mg/24h, depending on the stage of the disease).
clinic Screening activities, assessments
REDACTED COPY
clinic Screening activities, assessments, and training
REDACTED COPY
, and trainingto the Experimental Group only
REDACTED COPY
to the Experimental Group only) on Day
REDACTED COPY
) on Dayto the Experimental Group will use the Kinesia-360 device to record
REDACTED COPY
to the Experimental Group will use the Kinesia-360 device to record 2 and 3). REDACTED C
OPY
2 and 3).
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ed to record
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ed to record stage will
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
stage will Specific mo
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Specific moIn contrast to subjects
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
In contrast to subjects to the Experimental Group will also
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
to the Experimental Group will also ptoms.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ptoms.
All subjects will start Neupro treatment at a dose of either rotigotine 2mg/
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
All subjects will start Neupro treatment at a dose of either rotigotine 2mg/2
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
24h or 4mg/24h
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
4h or 4mg/24h ), which will then be adjusted based on s
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
), which will then be adjusted based on sia a combination of standard care
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ia a combination of standard care the Kinesia wearable technologies
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
the Kinesia wearable technologies. The Neupro dosing regimen used in PD0049 follows standard of care,
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
. The Neupro dosing regimen used in PD0049 follows standard of care, for rotigotine in the treatment of Parkinson’s
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
for rotigotine in the treatment of Parkinson’s disease (ie, up to 8mg/24h, depending on the stage of the disease).
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
disease (ie, up to 8mg/24h, depending on the stage of the disease).
clinic Screening activities, assessments
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
clinic Screening activities, assessments, and training
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
, and training in the use of Kinesia
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
in the use of Kinesia) on Day
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
) on Dayto the Experimental Group will use the Kinesia-360 device to record
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
to the Experimental Group will use the Kinesia-360 device to record 2 and 3).
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
2 and 3). Subjects allocated to the Control Group will start
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Subjects allocated to the Control Group will start y on Day
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y on DayExperimental group will start treatment with Neupro on Day
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Experimental group will start treatment with Neupro on Day12 (Visit 2).
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
12 (Visit 2). However,
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
However, are encouraged to discuss by
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
are encouraged to discuss by phone Kinesia
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
phone Kinesiaare encouraged to discuss by phone Kinesiaare encouraged to discuss by
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
are encouraged to discuss by phone Kinesiaare encouraged to discuss bychanges in Neupro dosing. Subjects of either group return to the cl
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
changes in Neupro dosing. Subjects of either group return to the cladverse events (
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
adverse events ( participation may
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
participation may
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
objective of PD0049 is to evaluate whether Parkinson’s disease motor sy
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
objective of PD0049 is to evaluate whether Parkinson’s disease motor sysubjects starting Neupro can be improved b
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
subjects starting Neupro can be improved b-360
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
-360 wearable technology
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
wearable technologyclinical practice as compared with onl
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
clinical practice as compared with onlevaluate whether a
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
evaluate whether a a subject’s Parkinson’s disease motor s
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
a subject’s Parkinson’s disease motor sthe Kinesia
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
the Kinesia
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 11 of 38
the quality of life and engagement in the management and treatment of their disease within subjects in either group, as well as to evaluate the safety of Neupro. The corresponding variables to be assessed to meet the study objectives are described in detail in Section 4.
2 INTRODUCTION
Neupro is approved for the treatment of the signs and symptoms of early-stage idiopathic Parkinson’s disease as monotherapy (ie, without levodopa) or in combination with levodopa, ie, over the course of the disease, through to late stages when the effect of levodopa wears off or becomes inconsistent and fluctuations of the therapeutic effect occur (end of dose or "on-off" fluctuations).
Dosing in patients with early-stage Parkinson’s disease consists of a single daily dose initiated at rotigotine 2mg/24h and then increased in weekly increments of rotigotine 2mg/24h to an effective dose up to a maximum dose of rotigotine 6mg/24h. Rotigotine 4mg/24h may be an effective dose in some patients. For most patients an effective dose is reached within 3 or 4 weeks at doses of rotigotine 6mg/24h. The maximum approved dose is rotigotine 6mg/24h(NEUPRO [package insert]. 2016 [Section 15]).
Dosing in patients with advanced-stage Parkinson’s disease with fluctuations consists of a single daily dose that should be initiated at rotigotine 4mg/24h and the increased in weekly increments of rotigotine 2mg/24h to an effective dose up to a maximum dose of rotigotine 8mg/24h. Rotigotine 4mg/24h or rotigotine 6mg/24h may be effective doses in some patients. For most patients with advanced-stage Parkinson’s disease, an effective dose is reached within 3 to 7 weeks at doses of rotigotine 8mg/24h. The maximum approved dose is rotigotine 8mg/24h(NEUPRO [package insert]. 2016 [Section 15]).
Optimal patient outcomes may be expected only when the clinician is able to prescribe a customized, optimal dosing regimen for patients with Parkinson’s disease. Clinicians employ various measures to diagnose Parkinson’s disease and its severity in order to prescribe the optimal dosing regimen for the patient. Key amongst these measures is an evaluation of the severity of the motor symptoms (eg, dyskinesia, gait, tremor, rigidity, and posture) associated with Parkinson’s disease. The quality of this evaluation (ie, quantification of movement) is critical to an accurate diagnosis of the evaluation of severity of the motor symptoms and is currently limited by the ability of the Clinician (through manual manipulation and observation) to accurately measure the various physical manifestations of motor symptoms associated withParkinson’s disease. Ultimately, the quality of the evaluation of the motor symptoms may determine whether the Clinician is able to prescribe the optimal dosing regimen for the patient.
New, wearable technologies that allow for accurate, consistent, and ongoing measurement of motor activity under ambulatory conditions in patients with Parkinson’s disease may provide the Clinician with additional motor symptom data that the Clinician could use to make more accurate evaluations of the motor symptoms associated with Parkinson’s disease, thereby providing the patient with the optimal Neupro dosing regimen and ensuring better patient outcomes in a more timely manner.
The focus of this 12-week study is on optimizing patients’ response to Neupro by using a commercially available wearable device to optimize the evaluation of motor symptoms and to improve customized dosing.
REDACTED COPY dose that should be initiated at rotigotine 4mg/24h and the increased in weekl
REDACTED COPY dose that should be initiated at rotigotine 4mg/24h and the increased in weekl
of rotigotine 2mg/24h to an effective dose up to a maximum dose of rotigotine 8mg/24h.
REDACTED COPY of rotigotine 2mg/24h to an effective dose up to a maximum dose of rotigotine 8mg/24h.
be effective doses in some patients. For most
REDACTED COPY
be effective doses in some patients. For most stage Parkinson’s disease, an effective dose is
REDACTED COPY
stage Parkinson’s disease, an effective dose is weeks at doses of rotigotine 8mg/24h. The maximum
REDACTED COPY
weeks at doses of rotigotine 8mg/24h. The maximum Section 15
REDACTED COPY
Section 15
be expected onlREDACTED C
OPY
be expected onlcustomized, optimal dosing regimen for patients with Parkinson’s disease. Clinicians employREDACTED C
OPY
customized, optimal dosing regimen for patients with Parkinson’s disease. Clinicians employ
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y (ie, without levodopa) or in combination with levodopa, ie,
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y (ie, without levodopa) or in combination with levodopa, ie, a wears off or
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
a wears off or off"
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
off"
dose initiated at
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
dose initiated at y increments of rotigotine 2mg/24h to an
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y increments of rotigotine 2mg/24h to an effective dose up to a maximum dose of rotigotine 6mg/24h. Rotigotine 4mg/24h may
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
effective dose up to a maximum dose of rotigotine 6mg/24h. Rotigotine 4mg/24h mayeffective dose in some patients. For most patients an effective dose is reached within 3 or
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
effective dose in some patients. For most patients an effective dose is reached within 3 or dose is rot
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
dose is roti
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
i
-stage Parkinson’s disease with fluctuations consists of a single
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
-stage Parkinson’s disease with fluctuations consists of a single dose that should be initiated at rotigotine 4mg/24h and the increased in weekl
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
dose that should be initiated at rotigotine 4mg/24h and the increased in weeklof rotigotine 2mg/24h to an effective dose up to a maximum dose of rotigotine 8mg/24h.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
of rotigotine 2mg/24h to an effective dose up to a maximum dose of rotigotine 8mg/24h. be effective doses in some patients. For most
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
be effective doses in some patients. For most stage Parkinson’s disease, an effective dose is
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
stage Parkinson’s disease, an effective dose is weeks at doses of rotigotine 8mg/24h. The maximum
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
weeks at doses of rotigotine 8mg/24h. The maximum ]).
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
]).
be expected onl
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
be expected only
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y customized, optimal dosing regimen for patients with Parkinson’s disease. Clinicians employ
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
customized, optimal dosing regimen for patients with Parkinson’s disease. Clinicians employvarious measures to diagnose Parkinson’s disease and its severity in o
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
various measures to diagnose Parkinson’s disease and its severity in ooptimal dosing regimen for the patient. Key
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
optimal dosing regimen for the patient. Keyy of the motor symptoms (eg, d
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y of the motor symptoms (eg, dwith Parkinson’s disease. The quality
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
with Parkinson’s disease. The qualitycritical to an accurate diagnosis of the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
critical to an accurate diagnosis of the y limited by the ability
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y limited by the abilityy measure
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y measure the various phy
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
the various phyParkinson’s disease.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Parkinson’s disease. Ultimately
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Ultimately
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
determine whether the Clinician is able to prescribe the optimal dosing regimen for the patient.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
determine whether the Clinician is able to prescribe the optimal dosing regimen for the patient.
New, wearable technologies that allow for accurate, consistent, and ongoing measurement of
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
New, wearable technologies that allow for accurate, consistent, and ongoing measurement of motor activity
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
motor activityClinician with additional motor symptom data that the Clinician coul
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Clinician with additional motor symptom data that the Clinician coul
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
evaluations of the motor sy
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
evaluations of the motor sypatient with the optimal Neupro dosing regimen and ensuring better patient outcomes in a more
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
patient with the optimal Neupro dosing regimen and ensuring better patient outcomes in a more
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 12 of 38
3 STUDY OBJECTIVES
3.1 Primary objectives
The primary objectives of this study are to:
Evaluate whether Parkinson’s disease motor symptoms in subjects starting Neupro can be improved by using feedback of motor symptom data from the Kinesia-360 wearable technology presented to subjects and Investigators in addition to standard clinical practice as compared with only standard clinical practice.
Evaluate the Neupro dosing regimen when using feedback of motor symptom data collected with the Kinesia-360 wearable technology in addition to standard clinical practice as compared with only standard clinical practice.
Evaluate whether subjects with Parkinson’s disease are more likely to continue the usage of Neupro if Parkinson’s disease motor symptom data collected using the Kinesia-360 wearable technology is used to provide the subjects with feedback on the status of their Parkinson’s disease motor symptoms and is used in addition to standard of care for titrating their Neupro dosing regimen.
3.2 Other objectives
Other objectives of this study are to:
Evaluate whether the quality of life of subjects with Parkinson’s disease can be improved by using the Kinesia-360 wearable technology to collect motor symptom data in addition to standard clinical practice as compared with only standard clinical practice to titrate the Neupro dosing regimen.
Evaluate whether subjects with Parkinson’s disease are more actively engaged in the management and treatment of their disease with Neupro therapy with the use of the Kinesia-360 wearable technology as compared to without the use of the Kinesia-360 wearable technology.
Evaluate the safety of Neupro.
REDACTED COPY
subject
REDACTED COPY
subjects with Parkinson’s disease can be improved b
REDACTED COPY
s with Parkinson’s disease can be improved bwearable technology
REDACTED COPY
wearable technology to collect motor sy
REDACTED COPY
to collect motor sywearable technology to collect motor sywearable technology
REDACTED COPY
wearable technology to collect motor sywearable technologystandard clinical practice as compared with only
REDACTED COPY
standard clinical practice as compared with only
with Parkinson’s disease are more actively engaged in the REDACTED COPY
with Parkinson’s disease are more actively engaged in the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
l practice as
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
l practice as
ptom data collected
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ptom data collected in addition to standard clinical practice as
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
in addition to standard clinical practice as
y to continue the usage of
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y to continue the usage of ptom data collected using the Kinesia-360
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ptom data collected using the Kinesia-360eedback on the status of their Parkinson’s
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
eedback on the status of their Parkinson’s ptoms and is used in addition to standard of care for titrating their Neupro
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ptoms and is used in addition to standard of care for titrating their Neupro
s with Parkinson’s disease can be improved b
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
s with Parkinson’s disease can be improved b to collect motor sy
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
to collect motor systandard clinical practice as compared with only
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
standard clinical practice as compared with only
with Parkinson’s disease are more actively engaged in the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
with Parkinson’s disease are more actively engaged in the management and treatment of their disease with Neupro therap
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
management and treatment of their disease with Neupro therap360 wearable technology
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
360 wearable technology as compared to without the use of the Kinesia
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
as compared to without the use of the Kinesia360 wearable technology as compared to without the use of the Kinesia360 wearable technology
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
360 wearable technology as compared to without the use of the Kinesia360 wearable technology
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y of Neupro.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y of Neupro.
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 13 of 38
4 STUDY VARIABLES
4.1 Efficacy variables
4.1.1 Primary efficacy variables
The efficacy variables of this study are:
Change from Baseline (Visit 1/Week 1) to Visit 2 (Week 12/3 months after start of treatment with Neupro) in Unified Parkinson’s Disease Rating Scale (UPDRS) Part III Motor Score
Change from Baseline (Visit 1/Week 1) to Visit 2 (Week 12) in Kinesia-ONE variables:
finger tapping speed score
rest tremor score
averaged finger tapping speed and resting tremor scores
postural tremor score
finger tapping amplitude score
hand grasp speed score
hand grasp amplitude score
rapid alternating movement speed score
rapid alternating amplitude score
dyskinesia score
Neupro dose per 24h at Visit 2 (Week 12)
Number of Neupro dose changes during the study (between Visit 1 and Visit 2)
Discontinuation of treatment with Neupro during the course of the study
4.1.2 Other efficacy variables
Change from Baseline to Visit 2 in the motor scores derived from the Kinesia-360 wearable technology by time (weekly/monthly) and by Neupro dose level (mg/24h) for the Experimental Group in:
average daily tremor score
average daily slowness score
average daily dyskinesia score
percent wear-time tremor detected
percent wear-time dyskinesia detected
percent wear-time user not moving
percent wear-time user was walking score
percent wear-time user active but not walking
REDACTED COPY
2 (WeekREDACTED COPY
2 (Week
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
treatment
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
treatment Motor Score
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Motor Score
ONE variables:
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ONE variables:
2 (Week
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
2 (Week 12)
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
12)
changes during the stud
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
changes during the stud
Discontinuation of treatment with Neupro during the course of the study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Discontinuation of treatment with Neupro during the course of the study
Other efficacy
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Other efficacy v
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
vOther efficacy vOther efficacy
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Other efficacy vOther efficacy ariables
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ariables
Change from Baseline to Visit
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Change from Baseline to Visity time (weekly
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y time (weeklyExperimental Group in:
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Experimental Group in:
average dail
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
average dail
average dail
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
average dail
average dail
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
average dail
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 14 of 38
number of steps per hour while wearing device
Change from Baseline to Visit 2 (Week 12) in the 39-Item Parkinson’s Disease Questionnaire (PDQ-39) scores.
Change from Baseline to Visit 2 (Week 12) in subject engagement questionnaire scores.
4.2 Safety variables
Safety variable is:
Occurrence of AEs
5 STUDY DESIGN
5.1 Study description
PD0049 is a multicenter, open-label, two-arm, 12-week study in subjects with Parkinson’s disease. On Day 1, eligible subjects will be randomized to either the Control Group or the Experimental Group in a 1:1 fashion. In both groups, subjects will use the Kinesia-ONE wearable device in-clinic at Visit 1 and Visit 2 for recording of specific motor symptoms, and subjects randomized to the Experimental Group will also use the Kinesia-360 wearable device at home while awake for continuous measurement of motor symptoms. The Investigator will use these symptom data to provide feedback to subjects on their motor symptoms and to supplement standard of care to titrate the optimal dose of Neupro for any given subject. In the Control Group, subjects will not use any wearable device at home, and the Investigator will use only standard of care to titrate the optimal Neupro dose.
Subjects in the Control Group and the Experimental Group will start treatment with Neupro 2mg/24h or 4mg/24h (at the Investigator’s discretion and according to the disease stage of the subject) preferably on Day 1 (but no later than Day 4) or Day 4, respectively. Evaluations conclude 12 weeks after the start of treatment with Neupro (ie, at Visit 2).
The decision to prescribe Neupro must be made by the Investigator independent of his/her decision to include the subject in the study. The subject’s treatment/Neupro intake must be within the terms of the marketing authorization; Neupro will not be supplied by UCB.
A schedule of study assessments is presented in Table 5‒1; for a detailed rationale of the study design see Section 5.3.
5.1.1 Study duration per subject
Each subject’s participation is approximately 12 weeks.
The end of the study is defined as the date of the last visit of the last subject in the study.
5.1.2 Planned number of subjects and sites
This study will be conducted in approximately 6 sites and will include a total of approximately 40 subjects (20 subjects in the Experimental Group and 20 subjects in the Control Group). Of note, a single site will not randomize more than 20 subjects.
REDACTED COPY for continuous measurement of motor sy
REDACTED COPY for continuous measurement of motor sy
vide feedback to subjects on their motor sy
REDACTED COPY vide feedback to subjects on their motor sy
standard of care to titrate the optimal dose of Neupro for an
REDACTED COPY
standard of care to titrate the optimal dose of Neupro for an wearable device at home, and the
REDACTED COPY
wearable device at home, and the andard of care to titrate the optimal Neupro dose.
REDACTED COPY
andard of care to titrate the optimal Neupro dose.
ontrol Group and the Experimental Group
REDACTED COPY
ontrol Group and the Experimental Groupnvestigator’s discretionREDACTED C
OPY
nvestigator’s discretionlaterREDACTED C
OPY
later
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
in subjects with Parkinson’s
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
in subjects with Parkinson’s to either the Control Group or the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
to either the Control Group or the will use the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
will use the Kinesia
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Kinesiaspecific motor
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
specific motor will also use the Kinesia
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
will also use the Kinesiafor continuous measurement of motor sy
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
for continuous measurement of motor symptoms. The
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
mptoms. The vide feedback to subjects on their motor sy
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
vide feedback to subjects on their motor systandard of care to titrate the optimal dose of Neupro for an
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
standard of care to titrate the optimal dose of Neupro for any
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y wearable device at home, and the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
wearable device at home, and the andard of care to titrate the optimal Neupro dose.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
andard of care to titrate the optimal Neupro dose.
ontrol Group and the Experimental Group
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ontrol Group and the Experimental Groupnvestigator’s discretion
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
nvestigator’s discretion
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
later
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
later than Day
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
than Dayweeks after the start of treatment with Neupro (ie, at Visit
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
weeks after the start of treatment with Neupro (ie, at Visit
The decision to prescribe Neupro must be made by the Investigator independent of his
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
The decision to prescribe Neupro must be made by the Investigator independent of histo include the subject in the study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
to include the subject in the studywithin the terms of the marketing authorization
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
within the terms of the marketing authorization
assessments is presented in
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
assessments is presented in Section 5.3
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Section 5.3
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
.
Study duration per
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Study duration per
Each subject’s participation is approximately
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Each subject’s participation is approximately
The end of the stud
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
The end of the stud
5.1.2
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
5.1.2
This study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This study40
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
40
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 15 of 38
5.1.3 Anticipated regions and countries
This study will be conducted in the US.
5.2 Schedule of study assessments
A schedule of assessments planned for both the Control Group and the Experimental group is presented in Table 5‒1.
REDACTED COPY
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 16 of 38
Table 5‒1: Schedule of study assessments
In Clinic At Home In Clinic
SCREENING BASELINE EOS/EW
Visit 1 Visit 2
Assessments Day 1Day 2-3
Day 4
Week 2
Week 3
Week 4
Week 11
Week 12
(±3 days)
Written informed consent X
Demographic data
(incl. height and weight)X Xa
Kinesia-ONE subject assessments (measured in triplicate) Xb X
UPDRS X X
Patient engagement questionnaire X X
PDQ-39 X X
Verification of inclusion/exclusion criteria X
Randomization X
C Group: Start treatment with Neupro 2mg or 4mg preferably on Day 1 but no later than Day 4 (dose adjustments during study are performed per standard of care)
X X
C Group: Record Neupro dose X X
E Group: Kinesia-360 device training and distribution of equipment
X
E Group: Subject wears Kinesia-360 wrist and ankle devices on Days 2 and 3 at home for baseline
X
E Group: Start treatment with Neupro 2mg or 4mg on X
REDACTED COPY
REDACTED COPY
REDACTED COPY
REDACTED COPY
REDACTED COPY
REDACTED COPY
X
REDACTED COPY
X
REDACTED COPY
REDACTED COPY
X
REDACTED COPY
X
REDACTED COPY
REDACTED COPY
REDACTED COPY
REDACTED COPY
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f. 16 Dec 2016
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f. 16 Dec 2016
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Week
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Week 2
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
2
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
X
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
X
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
X
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
X
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
preferably on Day 1 but no later than Day 4 (dose
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
preferably on Day 1 but no later than Day 4 (dose adjustments during study are performed per standard of
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
adjustments during study are performed per standard of
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
360 device training and distribution of
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
360 device training and distribution of
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Subject wears Kinesia
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Subject wears Kinesia-
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
-360 wrist and ankle
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
360 wrist and ankle devices on Days 2 and 3 at home for baseline
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
devices on Days 2 and 3 at home for baseline
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
reatment with Neupro 2mg or 4mg on
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
reatment with Neupro 2mg or 4mg on
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 17 of 38
Day 4
E Group: Record Neupro dosec X X
E Group: Reminder phone calls from site to subject at beginning of Weeks 2, 3, 4 and 11 (remind subject to charge devices and wear devices on at least 2 consecutive days during Weeks 2, 3, 4 and 11)
Xd Xd Xd Xd
E Group: Subject wears Kinesia-360 wrist and ankle devices on at least 2 consecutive days at home
X X X X
E Group: Subject and Investigator access Kinesia-360 device reports (subjects via device app, Investigators via GLNT web portal)
X X
E Group: Investigator combines standard of care withKinesia-360 motor symptom reports to adjust Neuprodose and is encouraged to contact the subject by phone to discuss motor symptom reports and potential Neuprodose adjustments anytime between V1 and V2 based on clinical judgment
X
E Group: Subject returns Kinesia-360 device equipment to site
X
Record adverse events X X
Record concomitant medications X X
APP=application; C Group=Control Group; E Group=Experimental Group; EOS=End of Study; EW=Early Withdrawal; GLNT=Great Lakes Neuro Technologies, Inc.; PDQ-39=39-Item Parkinson’s disease questionnaire; UPDRS=Unified Parkinson’s Disease Rating Scale; V=visit
a Only weight at V2. b The average of the triplicate resting tremor scores and triplicate finger tapping scores from Kinesia-ONE must be >1.0 to be eligible for inclusion in this study.c Subjects in the Experimental Group will be prompted to record Neupro dose in device app during each use of Kinesia-360 between V1 and V2. d Subjects in the Experimental Group are to use Kinesia-ONE on at least 2 consecutive days during Weeks 2, 3, 4 and 11, but are free to use the device as often
as they like between these time points prior to Visit 2.
REDACTED COPY
REDACTED COPY
REDACTED COPY
REDACTED COPY
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f. 16 Dec 2016
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f. 16 Dec 2016
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
X
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Xd
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
d
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
X X X X
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
X X X X
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Experi
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Experin’s disease
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
n’s disease
e average of the triplicate resting tremor scores and triplicate finger tapping scores from Kinesia
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
e average of the triplicate resting tremor scores and triplicate finger tapping scores from KinesiaSubjects in the Experimental Group will be prompted to record Neupro dose in device app dur
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Subjects in the Experimental Group will be prompted to record Neupro dose in device app dur
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Subjects in the Experimental Group are to use Kinesia
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Subjects in the Experimental Group are to use Kinesiaeen these time points prior to
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
een these time points prior to
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 18 of 38
5.3 Rationale for study design and selection of dose
The Neupro dosing regimen used in PD0049 follows standard of care, and is in line with the approved dosing regimen for rotigotine in the treatment of Parkinson’s disease (ie, up to 8mg/24h, depending on the stage of the disease).
As described in Section 2, the focus of this study is on optimizing the benefits of Neupro in patients with Parkinson’s disease by using wearable devices to help the Investigator optimize the evaluation of motor symptoms and improve customized dosing.
To that end, PD0049 employs Kinesia wearable technologies that allow for accurate, consistent, and ongoing measurement of motor activity under ambulatory conditions to provide the Investigator with additional information to further enhance his/her ability to evaluate subjects’ motor symptoms more accurately and, via providing the patient with the optimal Neupro dosing regimen, ensure better patient outcomes in a more timely manner. Both Kinesia devices will be used in accordance with their labelled instructions.
6 SELECTION AND WITHDRAWAL OF SUBJECTS
6.1 Inclusion criteria
To be eligible to participate in this study, all of the following criteria must be met:
1. Subject is newly prescribed Neupro and is expected to commence Neupro treatment.Historical Neupro treatment is permitted.
2. An Institutional Review Board (IRB) approved written Informed Consent form (ICF) is signed and dated by the subject, before any study-related procedures.
3. Subject is considered reliable and capable of adhering to the protocol, visit schedule, completion of the diary, and using Kinesia devices according to the judgment of the Investigator.
4. Male or female subject, ≥18 years of age at the time of the Screening Visit.
5. Subject has Parkinson’s disease, defined by the cardinal sign, bradykinesia, plus the presence of at least 1 of the following: tremor at rest, rigidity or impairment of postural reflexes, and without any other known or suspected cause of Secondary Parkinsonism.
6. Subject experiences motor symptoms associated with Parkinson’s disease that are not sufficiently controlled by current therapy. The average of the triplicate resting tremor scores and triplicate finger tapping scores from Kinesia-ONE (6 scores in total) must be >1.0.
6.2 Exclusion criteria
Subjects are not permitted to enroll in the study if any of the following criteria is met:
1. Subject is currently participating in any study with an investigational medicinal product(IMP) or investigational device.
2. Subject has any medical, neurological or psychiatric condition (eg, previous stroke, bipolar disorder, dementia, hallucinations, psychosis or severe depression, and drug or alcohol abuse) which, in the opinion of the Investigator, could jeopardize or would compromise the subject’s ability to participate in this study.
REDACTED COPY , all of the following criteria must
REDACTED COPY , all of the following criteria must
prescribed Neupro and is expected to commence Neupro treatment.
REDACTED COPY
prescribed Neupro and is expected to commence Neupro treatment.
An Institutional Review Board (IRB) approved written I
REDACTED COPY
An Institutional Review Board (IRB) approved written I, before
REDACTED COPY
, before an
REDACTED COPY
any stud
REDACTED COPY
y stud
is considered reliable and capable of adhering to the protocol, visit schedule, REDACTED C
OPY
is considered reliable and capable of adhering to the protocol, visit schedule, , and using Kinesia devices according to REDACTED C
OPY
, and using Kinesia devices according to
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Investigator optimize the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Investigator optimize the
s Kinesia wearable technologies that allow for accurate, consistent,
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
s Kinesia wearable technologies that allow for accurate, consistent, conditions to provide the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
conditions to provide the to evaluate subjects’
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
to evaluate subjects’ y and, via providing the patient with the optimal Neupro dosing
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y and, via providing the patient with the optimal Neupro dosing Both Kinesia devices will be
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Both Kinesia devices will be
SUBJECT
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
SUBJECT
, all of the following criteria must
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
, all of the following criteria must
prescribed Neupro and is expected to commence Neupro treatment.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
prescribed Neupro and is expected to commence Neupro treatment.
An Institutional Review Board (IRB) approved written I
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
An Institutional Review Board (IRB) approved written Iy stud
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y stud
is considered reliable and capable of adhering to the protocol, visit schedule,
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
is considered reliable and capable of adhering to the protocol, visit schedule,
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
, and using Kinesia devices according to
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
, and using Kinesia devices according to
ye
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
years
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ars
Subject has Parkinson’s disease, defined by
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Subject has Parkinson’s disease, defined byof the following: tremor at rest, rigidity
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
of the following: tremor at rest, rigidity other known or
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
other known or
Subject experiences motor sy
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Subject experiences motor sy
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
sufficiently
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
sufficiently controlled b
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
controlled btriplicate finger tapping scores from Kinesia-
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
triplicate finger tapping scores from Kinesia-
Subjects are not permitted to enroll in the study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Subjects are not permitted to enroll in the study
1.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
1. Subject is currentl
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Subject is currentl
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 19 of 38
3. Subject with Deep Brain Stimulation (DBS) device implant.
6.3 Withdrawal criteria
Subjects are free to withdraw from the study at any time, without prejudice to their continued care.
Subjects should be withdrawn from the study if any of the following events occur:
1. Subject develops an illness that would interfere with his/her continued participation.
2. Subject is noncompliant with the study procedures in the opinion of the Investigator.
3. Subject withdraws his/her consent.
4. The sponsor or a regulatory agency requests withdrawal of the subject.
For assessments to be performed in case of an Early Withdrawal, refer to Table 5‒1.
Investigators should attempt to obtain information on subjects in the case of withdrawal or discontinuation. For subjects considered as lost to follow up, the Investigator should make an effort (at least 1 phone call and 1 written message to the subject), and document his/her effort (date and summary of the phone call and copy of the written message in the source documents) to complete the final evaluation. All results of these evaluations and observations, together with a narrative description of the reason(s) for discontinuing the subject, including the date of discontinuation, must be recorded in the source documents. The electronic Case Report form (eCRF) must document the primary reason for withdrawal or discontinuation.
Investigators should contact the Medical Monitor, whenever possible, to discuss the withdrawal of a subject in advance.
For handling of dropouts, refer to Section 12.6.
7 MEDICINAL PRODUCT AND DEVICE
7.1 Description of medicinal product
Neupro (rotigotine) is a nonergolinic dopamine agonist for the treatment of the signs and symptoms of Parkinson’s disease and Restless Legs Syndrome (RLS). Neupro elicits its beneficial effect on Parkinson’s diseases by activation of the D3, D2 and D1 receptors of the caudate-putamen in the brain.
Neupro (Anatomical Therapeutic Chemical [ATC] code: N04BC09) is available as a transdermal system in six dosages. In the current study, Neupro is to be applied as prescribed by the Investigator and based on instructions provided in the patient leaflet/package insert (NEUPRO [package insert]. 2016 [Section 15]).
7.2 Devices
In the present study, all subjects will use the Kinesia-ONE device in-clinic during the Screening Visit for specific motor tasks/for recording of specific baseline motor symptoms. Subjectsrandomized to the Experimental Group will also use the Kinesia-360 device at home for continuous measurement of motor symptoms.
Kinesia-360 is intended to monitor physical motion and muscle activity to quantify kinematics of movement disorder symptoms such as tremor, and assess activity in any instance where
REDACTED COPY to complete the final evaluation. All results of these evaluations an
REDACTED COPY to complete the final evaluation. All results of these evaluations an
discontinuing
REDACTED COPY discontinuing the subject,
REDACTED COPY the subject,
must be recorded in the source documents. The electronic Case Report form
REDACTED COPY
must be recorded in the source documents. The electronic Case Report form or withdrawal
REDACTED COPY
or withdrawal
Investigators should contact the Medical Monitor, whenever possible, to discuss the withdrawal
REDACTED COPY
Investigators should contact the Medical Monitor, whenever possible, to discuss the withdrawal
Section 12.6REDACTED COPY
Section 12.6
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Table
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Table 5
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
5
Investigators should attempt to obtain information on subjects in the case of withdrawal
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Investigators should attempt to obtain information on subjects in the case of withdrawalInvestigator should make an
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Investigator should make an written message to the subject), and document his/her effort
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
written message to the subject), and document his/her effort of the written message in the source documents)
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
of the written message in the source documents) to complete the final evaluation. All results of these evaluations an
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
to complete the final evaluation. All results of these evaluations anthe subject,
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
the subject, must be recorded in the source documents. The electronic Case Report form
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
must be recorded in the source documents. The electronic Case Report form or withdrawal
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
or withdrawal
Investigators should contact the Medical Monitor, whenever possible, to discuss the withdrawal
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Investigators should contact the Medical Monitor, whenever possible, to discuss the withdrawal
Section 12.6
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Section 12.6
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
7 MEDICINAL PRODUCT AN
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
7 MEDICINAL PRODUCT AN
Description of medicinal product
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Description of medicinal product
Neupro (rotigotine) is a nonergolinic dopamine agonist for the treatment of the signs and
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Neupro (rotigotine) is a nonergolinic dopamine agonist for the treatment of the signs and mptoms of Parkinson’s disease and Restless Legs
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
mptoms of Parkinson’s disease and Restless Legsbeneficial effect on Parkinson’s diseases b
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
beneficial effect on Parkinson’s diseases bputamen in the brain.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
putamen in the brain.
Anatomical Therapeutic Chemical [
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Anatomical Therapeutic Chemical [in six dosages.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
in six dosages.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Investigator and based on instructions provided in the patient leaflet/package insert
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Investigator and based on instructions provided in the patient leaflet/package insert[package insert]. 2016
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
[package insert]. 2016
7.2
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
7.2
In the present stud
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
In the present studVisit
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Visit
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 20 of 38
quantifiable analysis of motion and muscle activity is desired. Kinesia Regulatory Certifications: Kinesia-One and Kinesia-360 have received US Food and Drug Administration (FDA) 510K clearance to market (06 Apr 2007), Conformité Européen Mark (European Medical Device Directive 93/42/EEC), Canadian Medical Device Conformity Assessment Systems, Australian Therapeutic Goods Association Certification, and International Organization for Standardization (ISO) 13485 (2003). Kinesia-One and Kinesia-360 are tested to International Electrotechnical Commission 60601 Standards, comply with Federal Communications Commission Part 15 Rules, and are Health Insurance Portability and Accountability Act compliant, and FDA Part 11 compliant for Electronic Data Capture in Clinical Trials.
7.2.1 Description of devices
Kinesia-ONE Wearable Sensor uses a subject-worn finger sensor and iPad mini application (APP) to objectively measure specific motor tasks related to Parkinson’s disease symptoms such as tremor, bradykinesia (slowed movements), and dyskinesia (involuntary movements) in the Investigator’s office. Subjects should wear the Kinesia-ONE device on the most affected side.
Kinesia-360 Wearable Sensor includes a wrist and ankle device, along with a cell phone, whichis also APP-based, and is designed for continuous day time monitoring of Parkinson’s disease symptoms. Subjects will wear Kinesia-360 while they go about their daily lives, and symptom severity is continually captured to enable objective assessment of Parkinson’s disease symptoms. Subjects should wear the Kinesia-360 device bands on the most affected side.
Symptom data recorded by either device, as well as the corresponding data reports, will be made available to the Investigators through a web portal.
The following variables will be derived from either Kinesia device to be used in PD0049:
Kinesia-ONE Kinesia-360
Change from Baseline to Visit 2 (Week 12) in the following Kinesia-ONE measures, which
will be averaged from triplicate repeated assessments at a measurement point:
Change from Baseline to Visit 2 (Week 12) in the following Kinesia-360 measures, which will be averaged from 2 consecutive days of
wear:
Resting tremor score Average daily tremor score
Postural tremor score Average daily slowness score
Finger tapping speed and amplitude scores Average daily dyskinesia score
Hand grasps speed and amplitude scores % wear-time tremor was detected
Rapid alternating movements speed and amplitude scores
% wear-time dyskinesia was detected
Dyskinesia score % wear-time user was not moving
% wear-time user was walking
REDACTED COPY y is continually captured to enable objective assessment of Parkinson’s disease s
REDACTED COPY y is continually captured to enable objective assessment of Parkinson’s disease s
Subjects should wear the Kinesia-360 device bands on the most affected side.
REDACTED COPY
Subjects should wear the Kinesia-360 device bands on the most affected side.
as well as the corresponding data reports
REDACTED COPY
as well as the corresponding data reportsavailable to the Investigators through a web portal.
REDACTED COPY
available to the Investigators through a web portal.
The following variables will be derived from either Kinesia device to be used in PD0049:
REDACTED COPY
The following variables will be derived from either Kinesia device to be used in PD0049:
REDACTED COPY
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
sensor and iPad mini
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
sensor and iPad mini application
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
application related to Parkinson’s disease s
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
related to Parkinson’s disease sym
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ymykinesia (slowed movements), and dyskinesia (involuntary movements) in the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ykinesia (slowed movements), and dyskinesia (involuntary movements) in the -ONE device on the most affected side.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
-ONE device on the most affected side.
includes a wrist and ankle device, along with a
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
includes a wrist and ankle device, along with a time monitoring of Parkinson’s disease
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
time monitoring of Parkinson’s disease go about their dail
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
go about their daily is continually captured to enable objective assessment of Parkinson’s disease s
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y is continually captured to enable objective assessment of Parkinson’s disease sSubjects should wear the Kinesia-360 device bands on the most affected side.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Subjects should wear the Kinesia-360 device bands on the most affected side.
as well as the corresponding data reports
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
as well as the corresponding data reportsavailable to the Investigators through a web portal.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
available to the Investigators through a web portal.
The following variables will be derived from either Kinesia device to be used in PD0049:
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
The following variables will be derived from either Kinesia device to be used in PD0049:
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
2 (Week
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
2 (Week
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
the following Kinesia-ONE measures, which
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
the following Kinesia-ONE measures, which averaged from triplicate
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
averaged from triplicateassessments at a measurement point:
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
assessments at a measurement point:
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Resting tremor scor
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Resting tremor scor
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Postural tremor score
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Postural tremor score
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Finger tapping speed and amplitude scores
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Finger tapping speed and amplitude scores
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Hand grasps speed and amplitude scores
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Hand grasps speed and amplitude scores
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 21 of 38
% wear-time user was active, but not walking
Number of steps/h while wearing the device
7.2.2 Packaging and labeling of the Kinesia devices
The sites will receive uniquely numbered wearable sensor devices (Kinesia-ONE and Kinesia-360) for use in the study. The devices will be provided in the intended final packaging.
7.2.3 Storage requirements
Sensor devices must be stored in a secured area with limited access at the Investigators’ sites.
7.2.4 Device accountability
Great Lakes Neuro Technologies, Inc. (GLNT) will supply the wearable sensor devices and associated equipment / software. The Investigator must ensure that the devices are used only in accordance with the manufacturer’s instructions. A device accountability form will be used to record the receipt and return dates of the wearable sensor devices and associated equipment/ software. In addition, dispensing and returning information on a by-subject basis will be completed. This form will serve as source documentation during the course of the study. Details of any device lost, not used, disposed of at the study site, or returned to the Sponsor must also be recorded. The Investigator, after completion of the study, will ensure that all devices are returned to GLNT.
7.3 Concomitant medications/treatments
Subjects will continue with their usual treatment. All medications/treatments (ie, Parkinson’s disease medications and others), including dosages, will be recorded in the appropriate study documents (ie, eCRF and source document).
Investigators are encouraged to adjust, if needed, the Neupro dose to optimize Parkinson’s disease symptoms. Back-titration of the Neupro dose in case of AEs is allowed as per standard of care.
Subjects are encouraged not to change the dosages of any concomitant medications during the study. There are no prohibited medications defined for this study.
7.3.1 Rescue medication
Not applicable.
7.4 Blinding
Not applicable.
7.5 Randomization and numbering of subjects
Subjects will be randomized (1:1) to either the Control Group (without Kinesia-360 device to measure motor symptoms at home) or the Experimental Group (with Kinesia-360 device to measure motor symptoms at home) during the Screening Visit (Visit 1). The randomization will be stratified by site. A randomization list for each site with a block size of 4 will be provided to
REDACTED COPY completed. This form will serve as source documentation during the course of the study
REDACTED COPY completed. This form will serve as source documentation during the course of the study
y device lost, not used, disposed of at the study site, or returned to the Sponsor must also be
REDACTED COPY
y device lost, not used, disposed of at the study site, or returned to the Sponsor must also be Investigator, after completion of the study
REDACTED COPY
Investigator, after completion of the study
Concomitant medications/treatments
REDACTED COPY
Concomitant medications/treatments
s will continue with their usual treatment. All medications/treatmentsREDACTED COPY
s will continue with their usual treatment. All medications/treatments
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
. The devices will be provided in the intended final packaging.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
. The devices will be provided in the intended final packaging.
at the Investigators’ sites.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
at the Investigators’ sites.
the wearable sensor devices and
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
the wearable sensor devices and associated equipment / software. The Investigator must ensure that the devices are used onl
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
associated equipment / software. The Investigator must ensure that the devices are used onlaccordance with the manufacturer’s instructions. A device accountability
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
accordance with the manufacturer’s instructions. A device accountabilityd return dates of the wearable sensor devices and associated equipment/
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
d return dates of the wearable sensor devices and associated equipment/ In addition, dispensing and returning information on a by-
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
In addition, dispensing and returning information on a by-completed. This form will serve as source documentation during the course of the study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
completed. This form will serve as source documentation during the course of the studyy device lost, not used, disposed of at the study site, or returned to the Sponsor must also be
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y device lost, not used, disposed of at the study site, or returned to the Sponsor must also be Investigator, after completion of the study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Investigator, after completion of the study, will ensure that all devices are returned
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
, will ensure that all devices are returned
Concomitant medications/treatments
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Concomitant medications/treatments
s will continue with their usual treatment. All medications/treatments
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
s will continue with their usual treatment. All medications/treatments, including dosages,
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
, including dosages,documents (ie, eCRF and source document).
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
documents (ie, eCRF and source document).
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Investigators are encouraged to
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Investigators are encouraged to
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
adjust
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
adjusttitration of the Neupro dose in case of
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
titration of the Neupro dose in case of
Subjects are encouraged not to change the dosages of any
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Subjects are encouraged not to change the dosages of any. There are no prohibited medications defined for this study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
. There are no prohibited medications defined for this study
Rescue medication
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Rescue medication
Not applicable.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Not applicable.
Not applicable.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Not applicable.
7.5
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
7.5
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 22 of 38
the site. Each subject will receive a 5-digit number assigned at Screening that serves as the subject identifier throughout the study.
8 STUDY PROCEDURES BY VISIT
Prior to the start of any study-related examinations or procedures, the written ICF must be signed and personally dated by the subject. The person (Investigator [or designee]) who conducted the informed consent discussion will document their informed consent process with his/her signature.
8.1 Visit 1 /Screening
The Screening examinations will be completed within 4 days, the first of which will take place at the study site (in clinic) and will include the following:
Day 1, in clinic:
Sign ICF
Control Group and Experimental Group: Subject wears Kinesia-ONE sensor on the most affected side in the clinic to measure specific motor tasks in triplicate. Calculation of the average of triplicate resting tremor scores and triplicate finger tapping speed scores (ie, 6 scores in total) must be >1.0 for subject inclusion in the study.
Verification of inclusion/exclusion criteria and collection of demographic data (includingweight and height)
PDQ-39
Investigator performs UPDRS assessment
Patient Engagement Questionnaire
Randomization (Control Group [without Kinesia-360 device use at home]/Experimental Group [with Kinesia-360 device use at home])
Experimental Group: Trained in-clinic on Kinesia-360 device (and sent home with the device)
Control Group: Start treatment with Neupro as prescribed (preferably on Day 1, but no later than Day 4); record date and dose
Control Group and Experimental Group: Recording of AEs and concomitant medications
8.2 Week 1
Day 2 and 3, home:
Experimental Group: Subject wears Kinesia-360 wrist and ankle devices on Days 2 and 3 at home for baseline
Experimental Group: Recording of concomitant medications and Neupro dose via APP
Day 4, home:
Experimental Group: Start treatment with Neupro as prescribed; record date and dose via APP
REDACTED COPY must be >1.0 for subject inclusion in the study
REDACTED COPY must be >1.0 for subject inclusion in the study
Verification of inclusion/exclusion criteria and collection of demographic data (incl
REDACTED COPY
Verification of inclusion/exclusion criteria and collection of demographic data (incl
UPDRS assessment
REDACTED COPY
UPDRS assessment
uestionnaireREDACTED C
OPY
uestionnaire
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
s, the first of which will take place at
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
s, the first of which will take place at
ONE
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ONEin triplicate. C
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
in triplicate. Cfinger tapping speed scores
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
finger tapping speed scores must be >1.0 for subject inclusion in the study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
must be >1.0 for subject inclusion in the study
Verification of inclusion/exclusion criteria and collection of demographic data (incl
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Verification of inclusion/exclusion criteria and collection of demographic data (incl
UPDRS assessment
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
UPDRS assessment
Randomization (Control Group [without Kinesia
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Randomization (Control Group [without Kinesia360 device
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
360 device use at home
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
use at home
Experimental Group: Trained in
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Experimental Group: Trained in
Control Group: Start treatment with Neupro as prescribed
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Control Group: Start treatment with Neupro as prescribed; record date and dose
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
; record date and dose
Control Group and Experimental Group: Recording of AEs and concomitant medications
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Control Group and Experimental Group: Recording of AEs and concomitant medications
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Day
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Day 2 and 3
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
2 and 3
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Experimental Group: Subject wears Kinesia-
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Experimental Group: Subject wears Kinesia-
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 23 of 38
Experimental Group: Recording of concomitant medications
8.3 Weeks 2, 3, and 4
Control Group, home:
Investigator uses standard of care to adjust Neupro dose as needed.
Phone contact initiated by subject or Investigator as needed. Documentation of any contact or dosage adjustment.
Experimental Group, home:
Subject uses Kinesia-360 at least on 2 consecutive days at home weekly to measure motor symptoms.
Subject accesses Kinesia-360 motor symptom reports on device following each day of measurements.
Investigator receives Kinesia-360 motor symptom reports via web portal following each day of measurements.
Investigator combines standard of care with weekly Kinesia-360 motor symptom reports to adjust Neupro dose as needed.
Phone contact initiated by subject or Investigator as needed and dispatch of Kinesia-360 motor symptom reports. Documentation of any contact or dosage adjustment.
Recording of concomitant medications and Neupro dose via APP.
A reminder phone call from the site to the subject each week during Weeks 2, 3, and 4 to ensure the subject will perform the protocol-requested Kinesia-360 assessments on 2 consecutive days per week. In addition, the subject should be reminded to charge the device and phone batteries the night prior to assessments.
8.4 Week 5 up to Week 12
Control Group, home:
Treatment of subjects as per standard of care.
Phone contact initiated by subject or Investigator as needed. Documentation of any contact or dosage adjustment.
Experimental Group, home:
A reminder phone call from the site to the subject during the week prior to Visit 2 to ensure the subject will perform the protocol-requested Kinesia-360 assessments on 2 consecutive days. In addition, the subject should be reminded to charge the device and phone batteries the night prior to assessments.
Optional: Subject may use Kinesia-360 as desired between Week 5 and Visit 2 (Week 12).
Subject receives Kinesia-360 motor symptom reports on device following each day of measurements.
REDACTED COPY
Investigator
REDACTED COPY
Investigator as needed and
REDACTED COPY
as needed and an
REDACTED COPY
any
REDACTED COPY
y contact or dosage adjustment.
REDACTED COPY
contact or dosage adjustment.
Recording of concomitant medications
REDACTED COPY
Recording of concomitant medications and Neupro dose
REDACTED COPY
and Neupro dose
A reminder phone call from the site to the subject each week during Weeks 2, 3
REDACTED COPY
A reminder phone call from the site to the subject each week during Weeks 2, 3ensure the subject will perform the protocolREDACTED C
OPY
ensure the subject will perform the protocol
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y contact or
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y contact or
to measure motor
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
to measure motor
on device following each day
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
on device following each day
via web portal following each
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
via web portal following each
Kinesia
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Kinesia-360
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
-360
as needed and
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
as needed and contact or dosage adjustment.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
contact or dosage adjustment.
and Neupro dose
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
and Neupro dose
A reminder phone call from the site to the subject each week during Weeks 2, 3
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
A reminder phone call from the site to the subject each week during Weeks 2, 3ensure the subject will perform the protocol
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ensure the subject will perform the protocol
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
n addition, the subject should be reminded to charge the device
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
n addition, the subject should be reminded to charge the device and phone batteries the night prior to assessments.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
and phone batteries the night prior to assessments.
up to
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
up to Week
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Week
Treatment of subjects as per standard of care.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Treatment of subjects as per standard of care.
Phone contact initiated by subject or
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Phone contact initiated by subject or adjustment.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
adjustment.
Experimental Group, home:
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Experimental Group, home:
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Experimental Group, home:
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Experimental Group, home:
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
A reminder phone call from the site to the sub
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
A reminder phone call from the site to the subthe subject will perform the protocol
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
the subject will perform the protocolday
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
day
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 24 of 38
Investigator receives Kinesia-360 motor symptom reports via web portal and by email following each day of measurements.
Treatment of patients as per standard of care and dispatch of any Kinesia-360 motor symptom report.
Phone contact initiated by subject or Investigator as needed and dispatch of Kinesia-360 motor symptom reports. Documentation of any contact or dosage adjustment.
8.5 Visit 2 (End of Study Visit) (Week 12 ±3 days)
Visit 2 represents the 3 month (from first Neupro dose) Follow-Up Visit.
Control Group and Experimental Group, in clinic:
Control Group and Experimental Group: Subject wears Kinesia-ONE sensor in the clinic on the same side assessed at Visit 1 to measure specific motor tasks in triplicate.
Investigator performs UPDRS assessment
Patient Engagement Questionnaire
Record Neupro dose
Complete questionnaire (PDQ-39)
Recording of AEs and concomitant medications
Experimental Group, in clinic:
Return Kinesia-360 equipment to site
8.6 Early Withdrawal Visit
In case of an Early Withdrawal Visit, the same assessments as planned for Visit 2 shall be performed (see Section 8.5).
9 ASSESSMENT OF EFFICACY
9.1 Inclusion criteria threshold related to tremor and/or bradykinesia
Based on prior experience with studies involving dopaminergic therapies, GLNT expectsbradykinesia and tremor to improve when using Neupro during PD0049. At Screening (ie, on Day 1), Investigators will perform the Kinesia-ONE assessment battery in triplicate on the more affected side of the body of each subject. As subjects will be on their individual Parkinson’s disease medication when entering the study, they will likely be in a relative “on” state. However, since these subjects will be newly prescribed Neupro as their Parkinson’s disease symptoms are not sufficiently controlled by their current therapy, it is likely that 1 or more symptoms will be present at Screening. To ensure subjects have sufficient room to improve, the inclusion criteria for this study include the presence of tremor and/or bradykinesia at Screening as measured by Kinesia-ONE. Specifically, based on experience in prior studies, the average of the triplicate resting tremor scores and the triplicate finger tapping scores (6 scores in total, averaged for 1 single score) must be >1.0 at Screening for subjects to be eligible for inclusion in this study (see Section 6.1, inclusion criterion #6).
REDACTED COPY
AEs and concomitant medications
REDACTED COPY
AEs and concomitant medications
to site
REDACTED COPY
to site
Withdrawal VisitREDACTED COPY
Withdrawal Visit
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ONE sensor in the clinic on
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ONE sensor in the clinic on the same side assessed at Visit 1 to measure specific motor tasks in triplicate.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
the same side assessed at Visit 1 to measure specific motor tasks in triplicate.
Withdrawal Visit
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Withdrawal Visit
y Withdrawal Visit, the same assessments as planned for Visit 2
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y Withdrawal Visit, the same assessments as planned for Visit 2
SESSMENT OF EFFICA
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
SESSMENT OF EFFICA
Inclusion criteria threshold related to tremor and/or
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Inclusion criteria threshold related to tremor and/or yki
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ykinesia
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
nesia
Based on prior exper
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Based on prior experience with studies involving dopaminergic therapies,
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ience with studies involving dopaminergic therapies, ykinesia and tremor to improve when using Neupro during PD0049. At Screening (ie, on
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ykinesia and tremor to improve when using Neupro during PD0049. At Screening (ie, on 1), Investigators will perform
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
1), Investigators will perform affected side of the bod
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
affected side of the bod
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
disease medication when entering the stud
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
disease medication when entering the studsince these subjects will be newl
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
since these subjects will be newlnot sufficiently
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
not sufficientlypresent at Screening.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
present at Screening.for this study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
for this study
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 25 of 38
9.1.1 Unified Parkinson’s Disease Rating Scale
The change from Baseline to Visit 2 (Week 12) in Part III UPDRS Motor Score will be utilized as a primary efficacy variable.
The UPDRS is a comprehensive assessment of symptoms in subjects with Parkinson’s disease. If possible, the same Investigator will perform both UPDRS assessments on a given subject. In PD0049, Parts I, II, and IV of the UPDRS will be used for the assessment of other efficacy variables.
9.1.2 39-Item Parkinson’s Disease Questionnaire
Another efficacy variable to be assessed is the change from Baseline to Visit 2 (Week 12) in PDQ-39 questionnaire scores.
In Parkinson’s disease, the PDQ-39 is the most widely used subject-reported rating scale endpoint in clinical studies.
10 ASSESSMENT OF SAFETY
10.1 Adverse events
10.1.1 Definitions
10.1.1.1 Adverse event
An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
In order to ensure complete safety data collection, all AEs occurring during the study (ie, after the signing of the ICF), including any pretreatment and posttreatment periods required by the protocol, must be reported in the eCRF even if no Neupro was taken but specific study procedures were conducted. This includes all AEs not present prior to the initial visit and all AEs that recurred or worsened after the initial visit.
Signs or symptoms of the condition/disease for which Neupro is being studied should be recorded as AEs only if their nature changes considerably or their frequency or intensity increases in a clinically significant manner as compared to the clinical profile known to the Investigator from the subject’s history or the pre-Neupro Period.
10.1.1.2 Serious adverse event
Once it is determined that a subject experienced an AE, the seriousness of the AE must be determined. A serious adverse event (SAE) must meet 1 or more of the following criteria:
Death
Life-threatening
(Life-threatening does not include a reaction that might have caused death had it occurred in a more severe form.)
REDACTED COPY
y untoward medical occurrence in a patient or clinical investigation subject
REDACTED COPY
y untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessaril
REDACTED COPY
administered a pharmaceutical product that does not necessarilre be any
REDACTED COPY
re be any unfavorable and unintended sign (including an
REDACTED COPY
unfavorable and unintended sign (including an re be any unfavorable and unintended sign (including an re be any
REDACTED COPY
re be any unfavorable and unintended sign (including an re be anyptom, or disease temporall
REDACTED COPY
ptom, or disease temporallmedicinal (investigational) product, whether or not related to the medicinal (investigational) REDACTED C
OPY
medicinal (investigational) product, whether or not related to the medicinal (investigational)
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
(Week
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
(Week 12) in
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
12) in
reported rating scale
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
reported rating scale
y untoward medical occurrence in a patient or clinical investigation subject
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessaril
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
administered a pharmaceutical product that does not necessaril unfavorable and unintended sign (including an
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
unfavorable and unintended sign (including an ptom, or disease temporall
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ptom, or disease temporallmedicinal (investigational) product, whether or not related to the medicinal (investigational)
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
medicinal (investigational) product, whether or not related to the medicinal (investigational)
er to ensure complete safety
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
er to ensure complete safety data collection, all AEs occurring during the study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
data collection, all AEs occurring during the studyer to ensure complete safety data collection, all AEs occurring during the studyer to ensure complete safety
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
er to ensure complete safety data collection, all AEs occurring during the studyer to ensure complete safety), including any pretreatment and posttreatment periods required b
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
), including any pretreatment and posttreatment periods required bprotocol, must be reported in the e
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
protocol, must be reported in the eprocedures were conducted. This includes all AEs not present prior to the initial visit and all AEs
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
procedures were conducted. This includes all AEs not present prior to the initial visit and all AEs that recurred or worsened after the initial visit.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
that recurred or worsened after the initial visit.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ptoms of the condition/disease for which
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ptoms of the condition/disease for which corded as AEs only if their nature changes considerabl
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
corded as AEs only if their nature changes considerablincreases in a clinicall
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
increases in a clinicallnvestigator from the subject’s history
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
nvestigator from the subject’s history
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
10.1.1.2
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
10.1.1.2
Once it is determined that a subject experienced an AE, the seriousness of the AE must be
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Once it is determined that a subject experienced an AE, the seriousness of the AE must be
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
determined.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
determined.
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 26 of 38
Significant or persistent disability/incapacity
Congenital anomaly/birth defect (including that occurring in a fetus)
Important medical event that, based upon appropriate medical judgment, may jeopardize the patient or subject and may require medical or surgical intervention to prevent 1 of the other outcomes listed in the definition of serious
(Important medical events may include, but are not limited to, potential Hy’s Law, allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias that do not result in inpatient hospitalization, or the development of drug dependency or drug abuse.)
Initial inpatient hospitalization or prolongation of hospitalization
(A patient admitted to a hospital, even if he/she is released on the same day, meets the criteria for the initial inpatient hospitalization. An emergency room visit that results in admission to the hospital would also qualify for the initial inpatient hospitalization criteria. However, emergency room visits that do not result in admission to the hospital would not qualify for this criteria and, instead, should be evaluated for 1 of the other criteria in the definition of serious [eg, life-threatening adverse experience, important medical event].
Hospitalizations for reasons not associated with the occurrence of an AE [eg, preplanned surgery or elective surgery for a pre-existing condition that has not worsened or manifested in an unusual or uncharacteristic manner] do not qualify for reporting. For example, if a subject has a condition recorded on his/her medical history and later has a preplanned surgery for this condition, it is not appropriate to record the surgery or hospitalization as an SAE, since there is no AE upon which to assess the serious criteria. Please note that, if the pre-existing condition has worsened or manifested in an unusual or uncharacteristic manner, this would then qualify as an AE and, if necessary, the seriousness of the event would need to be determined.)
10.1.1.3 Adverse events of special interest
Not applicable.
10.1.2 Procedures for reporting and recording adverse events and other safety related information
The Investigator is requested to instruct participating subjects of the need to inform them of any AE or other safety related information during the study, regardless of the relationship to medication, device use, or study procedures.
The subject will be given the opportunity to report AEs spontaneously. A general prompt will also be given at each study visit to detect AEs. For example:
“Did you notice anything unusual about your health (since your last visit)?”
In addition, the Investigator should review any self-assessment procedures (eg, diary cards) employed in the study.
REDACTED COPY Hospitalizations for reasons not associated with the occurrence of an AE [eg,
REDACTED COPY Hospitalizations for reasons not associated with the occurrence of an AE [eg,
-existing condition that has not worsened or manifested
REDACTED COPY
-existing condition that has not worsened or manifested haracteristic manner] do not qualify
REDACTED COPY
haracteristic manner] do not qualifysubject has a condition recorded on his/her medical history
REDACTED COPY
subject has a condition recorded on his/her medical historyfor this condition, it is not appropriate to record the surgery
REDACTED COPY
for this condition, it is not appropriate to record the surgerysince there is no AE upon which to assess the serious criteria. Please note that, if the
REDACTED COPY
since there is no AE upon which to assess the serious criteria. Please note that, if the -existing condition has worsened or manifested in an unusual or uncharacteristic manner, REDACTED C
OPY
-existing condition has worsened or manifested in an unusual or uncharacteristic manner,
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
rgic
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
rgic
(A patient admitted to a hospital, even if he/she is released on the same day
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
(A patient admitted to a hospital, even if he/she is released on the same day, meets the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
, meets the room visit that results in
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
room visit that results in inpatient hospitalization criteria.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
inpatient hospitalization criteria. room visits that do not result in admission to the hospital would not
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
room visits that do not result in admission to the hospital would not for this criteria and, instead, should be evaluated for 1 of the other criteria in the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
for this criteria and, instead, should be evaluated for 1 of the other criteria in the atening adverse experience, important medical event].
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
atening adverse experience, important medical event].
Hospitalizations for reasons not associated with the occurrence of an AE [eg,
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Hospitalizations for reasons not associated with the occurrence of an AE [eg,-existing condition that has not worsened or manifested
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
-existing condition that has not worsened or manifested haracteristic manner] do not qualify
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
haracteristic manner] do not qualifysubject has a condition recorded on his/her medical history
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
subject has a condition recorded on his/her medical historyfor this condition, it is not appropriate to record the surgery
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
for this condition, it is not appropriate to record the surgerysince there is no AE upon which to assess the serious criteria. Please note that, if the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
since there is no AE upon which to assess the serious criteria. Please note that, if the -existing condition has worsened or manifested in an unusual or uncharacteristic manner,
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
-existing condition has worsened or manifested in an unusual or uncharacteristic manner, as an AE and, if necessary, the seriousness of t
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
as an AE and, if necessary, the seriousness of t
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
verse events of special interest
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
verse events of special interest
Procedures for reporting and recording adverse events
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Procedures for reporting and recording adverse eventssafety
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
safety related information
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
related informationsafety related informationsafety
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
safety related informationsafety
The Investigator is requested to
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
The Investigator is requested to AE or other safet
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
AE or other safety related information during the study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y related information during the studymedication, device use, or study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
medication, device use, or study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
The subject will be given the opportunity
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
The subject will be given the opportunityalso be given at each study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
also be given at each study
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 27 of 38
10.1.2.1 Description of adverse events
When recording an AE, the Investigator should use the overall diagnosis or syndrome using standard medical terminology, rather than recording individual symptoms or signs. The eCRF and source documents should be consistent. Any discrepancies between the subject’s own words on his/her own records (eg, diary card) and the corresponding medical terminology should be clarified in the source documentation.
Details for completion of the AE eCRF (including judgment of relationship to Neupro) are described in the eCRF Completion Guidelines.
10.1.2.2 Rule for repetition of an adverse event
An increase in the intensity of an AE should lead to the repetition of the AE being reported with:
The outcome date of the first AE that is not related to the natural course of the disease being the same as the start date of the repeated AE, and the outcome of “worsening”
The AE verbatim term being the same for the first and repeated AE, so that the repeated AE can be easily identified as the worsening of the first one
Details for completion of the AE are described in the eCRF Completion Guidelines.
10.1.2.3 Reporting of serious AEs (related or not to Neupro)
An Investigator shall submit to UCB a report of any SAE experienced by a study subject, whether or not considered related to the participation in the study (ie, associated or not with Neupro) within 24 hours after the Investigator first learns of the event using the appropriate form.
Every effort shall be made to report the following information: date of AE, treatment/action taken, resolution, assessment of both the seriousness and the relationship to Neupro.
10.1.2.4 Device reporting
Great Lakes Neuro Technologies, Inc. will follow FDA medical device reporting requirements per 21CFR803. Sites will report adverse device effects and device deficiencies directly to GLNT ( : Office: [9:00am – 5:00pm EST]; Mobile: [after business hours]; email: ). An adverse device event (ADE) is defined as any AE related to the use of a device. A device deficiency is defined as inadequacy of a device with respect to its identity, quality, durability, reliability, safety, or performance. Great Lakes Neuro Technologies, Inc. will share this information with UCB.
10.1.3 Follow up of adverse events
An AE should be followed until it has resolved, has a stable sequelae, the Investigator determines that it is no longer clinically significant, or the subject is lost to follow up. This follow-up requirement applies to AEs and SAEs.
If an AE is ongoing at the end of the study for a subject, follow up should be provided until resolution/stable level of sequelae is achieved, or until the Investigator no longer deems that it is clinically significant, or until the subject is lost to follow up. If no follow up is provided, the Investigator must provide a justification. The follow up will usually be continued for 30 daysafter the subject has discontinued treatment with Neupro.
REDACTED COPY Es (related or not to
REDACTED COPY Es (related or not to
An Investigator shall submit to UCB a report of any
REDACTED COPY
An Investigator shall submit to UCB a report of any S
REDACTED COPY SAE experienced b
REDACTED COPY
AE experienced brelated to the participation in the study
REDACTED COPY
related to the participation in the study) within 24 hours after the Investigator first learns of the event using the appropriate
REDACTED COPY
) within 24 hours after the Investigator first learns of the event using the appropriate
effort shall be made to report the following information: date of AE, treatmentREDACTED COPY
effort shall be made to report the following information: date of AE, treatmenttaken, resolution, assessment of both the seriousness and the relationship to REDACTED C
OPY
taken, resolution, assessment of both the seriousness and the relationship to
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
of an AE should lead to the repetition of the AE being reported with:
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
of an AE should lead to the repetition of the AE being reported with:
atural course of the disease being
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
atural course of the disease being the same as the start date of the repeated AE, and the outcome of “worsening”
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
the same as the start date of the repeated AE, and the outcome of “worsening”
The AE verbatim term being the same for the first and repeated AE, so that the repeated AE
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
The AE verbatim term being the same for the first and repeated AE, so that the repeated AE
Details for completion of the AE are described in the eCRF Completion Guidelines.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Details for completion of the AE are described in the eCRF Completion Guidelines.
Es (related or not to
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Es (related or not to
AE experienced b
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
AE experienced brelated to the participation in the study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
related to the participation in the study) within 24 hours after the Investigator first learns of the event using the appropriate
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
) within 24 hours after the Investigator first learns of the event using the appropriate
effort shall be made to report the following information: date of AE, treatment
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
effort shall be made to report the following information: date of AE, treatmenttaken, resolution, assessment of both the seriousness and the relationship to
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
taken, resolution, assessment of both the seriousness and the relationship to
Device reporting
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Device reporting
Great Lakes Neuro Technologies
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Great Lakes Neuro Technologies, Inc.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
, Inc.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
803. Sites will report adverse device e
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
803. Sites will report adverse device e
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
: Office:
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
: Office: ]; email:
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
]; email: y AE related to the use of a device. A device deficiency is defined as inadequacy of
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y AE related to the use of a device. A device deficiency is defined as inadequacy of a device with respect to its identity
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
a device with respect to its identityLakes Neuro Technologies
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Lakes Neuro Technologies
An AE should be followed until it has resolv
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
An AE should be followed until it has resolv
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
determines that it is no longer clinically significant, or the subject is lost to follow up.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
determines that it is no longer clinically significant, or the subject is lost to follow up. follow
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
follow
If an AE is ongoing at the end of the study for a subject, follow up should be provided until
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
If an AE is ongoing at the end of the study for a subject, follow up should be provided until
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 28 of 38
Information on SAEs obtained after clinical database lock will be captured through the Patient Safety (PS) database without limitation of time.
10.1.4 Pregnancy and breastfeeding
Investigators are required to report pregnancy of a subject, pregnancy of a subject’s partner, and a subject who is breastfeeding using the Pregnancy Report and Outcome form for postmarketing cases. The procedure for reporting a pregnancy or breastfeeding is identical to the procedure for reporting safety relevant information (see Section 10.1.2.3).
The progression of the pregnancy and the eventual birth (if applicable) must be followed up using the same form in which the Investigator has to report on the health of the mother and of the child. Every reasonable attempt should be made to follow the development and health of the child for at least 30 days after birth for any significant medical issues or development delay.
If the subject is lost to follow up and/or refuses to give information, written documentation of attempts to contact the subject needs to be provided by the Investigator and filed at the site.
In cases where the partner of a male subject enrolled in this study becomes pregnant, the Investigator or designee is asked to contact the subject to request consent of the partner via the Partner Pregnancy Consent form that should be available in the Investigator’s site file. The Investigator will complete the Pregnancy Report and Outcome form for postmarketing cases and send it to UCB only after the partner has agreed that additional information can be captured and has provided the signed Partner Pregnancy Consent form.
10.1.5 Overdose of medicinal product
Excessive dosing (beyond that prescribed in the protocol and including overdose) should be recorded in the eCRF. Any SAE or nonserious AE associated with excessive dosing must be followed as any other SAE or nonserious AE. These events are only considered AEs or SAEs if there are associated clinical signs and symptoms or if the act of taking the excess medicine itself is an AE or SAE (eg, suicide attempt).
Further details on Neupro overdosing can be found in the label (NEUPRO [package insert]. 2016[Section 15]).
10.2 Laboratory measurements
Not applicable.
10.3 Other safety measurements
10.3.1 Rate of discontinuation of treatment with Neupro
The comparison of the rate of discontinuation of treatment with Neupro during the course of the study for the Control Group and the Experimental Group is one of the safety variables in PD0049.
Subjects who discontinue treatment with Neupro are encouraged to attend an Early Withdrawal Visit (see Section 8.6). For subjects randomized to the Experimental Group, discontinuation of treatment with Neupro can also be captured via the Kinesia-360 diary medication section within the respective APP.
REDACTED COPY Report and Outcome form for p
REDACTED COPY Report and Outcome form for p
after the partner has agreed that additional information can be captured and
REDACTED COPY
after the partner has agreed that additional information can be captured and Consent form.
REDACTED COPY
Consent form.
Overdose of medicinal product
REDACTED COPY
Overdose of medicinal product
ond that prescribed in the protocol an
REDACTED COPY
ond that prescribed in the protocol an
REDACTED COPY
SAE or nonserious AE associated with excessive dosing must be REDACTED C
OPY
SAE or nonserious AE associated with excessive dosing must be y other SAE or nonserious AE. These events are onlREDACTED C
OPY
y other SAE or nonserious AE. These events are onl
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
or breastfeeding is identical to the procedure for
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
or breastfeeding is identical to the procedure for
and the eventual birth (if applicable) must be followed up
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
and the eventual birth (if applicable) must be followed up of the mother and of the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
of the mother and of the reasonable attempt should be made to follow the development and health of the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
reasonable attempt should be made to follow the development and health of the significant medical issues or development delay
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
significant medical issues or development delay
refuses to give information, written documentation of
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
refuses to give information, written documentation of the Investigator and filed at the site.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
the Investigator and filed at the site.
becomes pregnant, the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
becomes pregnant, the designee is asked to contact the subject to request consent of the partner via the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
designee is asked to contact the subject to request consent of the partner via the Consent form that should be available in the Investigator’s site file. The
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Consent form that should be available in the Investigator’s site file. The Report and Outcome form for p
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Report and Outcome form for p after the partner has agreed that additional information can be captured and
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
after the partner has agreed that additional information can be captured and Consent form.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Consent form.
Overdose of medicinal product
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Overdose of medicinal product
ond that prescribed in the protocol an
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ond that prescribed in the protocol an
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
SAE or nonserious AE associated with excessive dosing must be
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
SAE or nonserious AE associated with excessive dosing must be y other SAE or nonserious AE. These events are onl
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y other SAE or nonserious AE. These events are onlthere are associated clinical signs and s
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
there are associated clinical signs and sym
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ymsuicide attempt).
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
suicide attempt).
Further details on Neupro overdosing can be found in the label
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Further details on Neupro overdosing can be found in the label
Laboratory
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Laboratory
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Other safety
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Other safety
Rate of discontinuation of treatment with Neupro
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Rate of discontinuation of treatment with Neupro
The comparison of the rate of discontinuation of treatment with Neupro
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
The comparison of the rate of discontinuation of treatment with Neuprostudy
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
for the Control Group and the Experimental Group is one of the safety
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
for the Control Group and the Experimental Group is one of the safetystudy for the Control Group and the Experimental Group is one of the safetystudy
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
study for the Control Group and the Experimental Group is one of the safetystudyPD0049.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
PD0049.
Subjects who discontinue treatment with Neupro are encouraged to attend an Earl
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Subjects who discontinue treatment with Neupro are encouraged to attend an Earl
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 29 of 38
11 STUDY MANAGEMENT AND ADMINISTRATION
11.1 Adherence to protocol
The Investigator should not deviate from the protocol. However, the Investigator should take any measure necessary in deviation from or not defined by the protocol in order to protect clinical study subjects from any immediate hazard to their health and safety. In this case, this action should be taken immediately, without prior notification of the regulatory authority, IRB, or sponsor.
After implementation of such measure, the Investigator must notify the Clinical Project Managerof the sponsor within 24 hours and follow any local regulatory requirements.
11.2 Monitoring
UCB (or designee) will monitor the study to meet the sponsor’s monitoring Standard Operating Procedures (SOPs), International Council for Harmonisation-Good Clinical Practice (ICH-GCP)guideline, and applicable regulatory requirements, and to ensure that study initiation, conduct, and closure are adequate. Monitoring of the study may be delegated by UCB to a Contract Research Organziation (CRO) or a contract monitor.
The Investigator and his/her staff are expected to cooperate with UCB (or designee) and to be available during the monitoring visits to answer questions sufficiently and to provide any missing information. The Investigator(s)/institution(s) will permit direct access to source data/documents for study-related monitoring, audits, IRB review, and regulatory inspection(s).
The Investigator will allow UCB (or designee) to periodically review all eCRFs and corresponding source documents (eg, hospital and laboratory records for each study participant). Monitoring visits will provide UCB (or designee) with the opportunity to evaluate the progress of the study, verify the accuracy and completeness of eCRFs, ensure that all protocol requirements, applicable authorities regulations, and Investigator’s obligations are being fulfilled, and resolve any inconsistencies in the study records.
11.2.1 Definition of source data
Source documents are original records in which raw data are first recorded. These may include hospital/clinic/general practitioner records, charts, diaries, x-rays, laboratory results, printouts, pharmacy records, care records, electrocardiogram (ECG) or other printouts, completed scales, or quality of life questionnaires. Source documents should be kept in a secure, limited access area.
Source documents that are computer generated and stored electronically must be printed for review by the monitor (eg, ECG reports). Once printed, these copies should be signed and dated by the Investigator and become a permanent part of the subject’s source documents. The Investigator will facilitate the process for enabling the monitor to compare the content of the printout and the data stored in the computer to ensure all data are consistent.
Electronic data records, such as Holter monitor records or electroencephalogram records, must be saved and stored as instructed by UCB (or designee).
REDACTED COPY nvestigator and his/her staff are expected to cooperate with UCB (or designee) and to
REDACTED COPY nvestigator and his/her staff are expected to cooperate with UCB (or designee) and to
available during the monitoring visits to answer questions sufficiently
REDACTED COPY available during the monitoring visits to answer questions sufficiently
nvestigator(s)/institution(s) will permit direct access to source
REDACTED COPY
nvestigator(s)/institution(s) will permit direct access to source related monitoring, audits, I
REDACTED COPY
related monitoring, audits, I
Investigator will allow UCB (or designee) to periodicall
REDACTED COPY
Investigator will allow UCB (or designee) to periodicallhospital and laboratory
REDACTED COPY
hospital and laboratoryMonitoring visits will provide UCB (or designee) wi
REDACTED COPY
Monitoring visits will provide UCB (or designee) wi and completeness of REDACTED C
OPY
and completeness of
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Clinical Project Manager
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Clinical Project Manager
to meet the sponsor’s monitoring Standard Operating
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
to meet the sponsor’s monitoring Standard Operating Good Clinical Practice (
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Good Clinical Practice (tudy
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
tudy initiation, conduct,
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
initiation, conduct, tudy initiation, conduct, tudy
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
tudy initiation, conduct, tudy be delegated by
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
be delegated by UCB to a
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
UCB to a be delegated by UCB to a be delegated by
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
be delegated by UCB to a be delegated by
nvestigator and his/her staff are expected to cooperate with UCB (or designee) and to
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
nvestigator and his/her staff are expected to cooperate with UCB (or designee) and to available during the monitoring visits to answer questions sufficiently
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
available during the monitoring visits to answer questions sufficientlynvestigator(s)/institution(s) will permit direct access to source
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
nvestigator(s)/institution(s) will permit direct access to source related monitoring, audits, I
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
related monitoring, audits, IRB review, and r
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
RB review, and r
Investigator will allow UCB (or designee) to periodicall
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Investigator will allow UCB (or designee) to periodicallhospital and laboratory
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
hospital and laboratoryMonitoring visits will provide UCB (or designee) wi
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Monitoring visits will provide UCB (or designee) wi and completeness of
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
and completeness of requirements, applicable authorities regulations, and Investigator’s obligations are being
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
requirements, applicable authorities regulations, and Investigator’s obligations are being y inconsis
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y inconsistencies in the study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
tencies in the study
Definition of source data
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Definition of source data
Source documents are original records in which raw data are first recorded. These may
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Source documents are original records in which raw data are first recorded. These mayhospital/clinic/general practitioner records, charts, diar
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
hospital/clinic/general practitioner records, charts, diar records, care records,
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
records, care records, of life questionnaires. Source documents should be kept in a secure, limited access
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
of life questionnaires. Source documents should be kept in a secure, limited access
Source documents that are computer generated and stored electron
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Source documents that are computer generated and stored electronreview b
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
review by the monitor (
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y the monitor (
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
the I
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Investigator and become a permanent part of the subject’s source documents. The
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
nvestigator and become a permanent part of the subject’s source documents. The I
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Investigator will facilitate the process for en
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
nvestigator will facilitate the process for enprintout and the data stored in the computer to ensure all data are consistent.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
printout and the data stored in the computer to ensure all data are consistent.
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 30 of 38
11.2.2 Source data verification
Source data verification ensures accuracy and credibility of the data obtained. During monitoring visits, reported data are reviewed with regard to being accurate, complete, and verifiable from source documents (eg, subject files, recordings from automated instruments, tracings [ECG], x-ray films, laboratory notes). All data reported on the eCRF should be supported by source documents, unless otherwise specified in Section 11.2.1.
11.3 Data handling
11.3.1 Case Report form completion
The Investigator is responsible for prompt reporting of accurate, complete, and legible data in the eCRFs and in all required reports.
Any change or correction to the eCRF after saving must be accompanied by a reason for the change.
Corrections made after the Investigator’s review and approval (by means of a password/electronic signature) will be reapproved by the Investigator.
The Investigator should maintain a list of personnel authorized to enter data into the eCRF.
Detailed instructions will be provided in the eCRF Completion Guidelines.
11.3.2 Database entry and reconciliation
Case Report forms/external electronic data will be entered/loaded into a validated electronic database using a clinical data management system (CDMS). Computerized data cleaning checks will be used in addition to manual review to check for discrepancies and to ensure consistency of the data. The data are entered into the eCRFs once and are subsequently verified.
An electronic audit trail system will be maintained within the CDMS to track all data changes in the database once the data have been saved initially into the system or electronically loaded. Regular backups of the electronic data will be performed.
11.3.3 Subject Screening and Enrollment log/Subject Identification Code list
The subject’s screening and enrollment will be recorded in the Subject Screening and Enrollment Log.
The Investigator will keep a Subject Identification Code list. This list remains with the Investigator and is used for unambiguous identification of each subject.
The subject’s consent and enrollment in the study must be recorded in the subject’s medical record. These data should identify the study and document the dates of the subject’s participation.
11.4 Termination of the study
UCB reserves the right to temporarily suspend or prematurely discontinue this study either at a single site, multiple sites, or at all sites at any time for reasons including, but not limited to, safety or ethical issues, inaccurate or incomplete data recording, noncompliance, or unsatisfactory enrollment with respect to quality or quantity.
REDACTED COPY CRF Completion Guidelines.
REDACTED COPY CRF Completion Guidelines.
and reconciliation
REDACTED COPY
and reconciliation
lectronic data will be entered/loaded into a validated electronic
REDACTED COPY
lectronic data will be entered/loaded into a validated electronic database using a clinical data management sy
REDACTED COPY
database using a clinical data management system (CDMS). Computerized data cleaning checks
REDACTED COPY
stem (CDMS). Computerized data cleaning checks will be used in addition to manual review to check for discrepancies and to ensure consistency
REDACTED COPY
will be used in addition to manual review to check for discrepancies and to ensure consistencyThe data are entered into the
REDACTED COPY
The data are entered into the eCRFsREDACTED C
OPY
eCRFs
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Investigator is responsible for prompt reporting of accurate, complete, and legible data in th
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Investigator is responsible for prompt reporting of accurate, complete, and legible data in th
y a reason for the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y a reason for the
y means of a
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y means of a nvestigator.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
nvestigator.
nvestigator should maintain a list of personnel authorized to enter data into the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
nvestigator should maintain a list of personnel authorized to enter data into the
CRF Completion Guidelines.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
CRF Completion Guidelines.
and reconciliation
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
and reconciliation
lectronic data will be entered/loaded into a validated electronic
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
lectronic data will be entered/loaded into a validated electronic stem (CDMS). Computerized data cleaning checks
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
stem (CDMS). Computerized data cleaning checks will be used in addition to manual review to check for discrepancies and to ensure consistency
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
will be used in addition to manual review to check for discrepancies and to ensure consistencyeCRFs
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
eCRFs once and are subsequentl
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
once and are subsequentl
An electronic audit trail system will be maintained within the CDMS to track all data changes in
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
An electronic audit trail system will be maintained within the CDMS to track all data changes in
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
the database once the data have been saved initially
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
the database once the data have been saved initiallyRegular backups of the electronic data will be performed.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Regular backups of the electronic data will be performed.
Subject Screening and Enrollment log/Subject Identification Code list
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Subject Screening and Enrollment log/Subject Identification Code list
The subject’s screening and enrollment will be recorded in the Subject Screening and Enrollment
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
The subject’s screening and enrollment will be recorded in the Subject Screening and Enrollment
nvestigator will keep a Subject Identification Code list. This list remains with the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
nvestigator will keep a Subject Identification Code list. This list remains with the Investigator and is used for unambiguous identification of each subject.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Investigator and is used for unambiguous identification of each subject.
The subject’s consent and enrollment in the study must be recorded in the subject’s medical
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
The subject’s consent and enrollment in the study must be recorded in the subject’s medical
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
. These data should identify
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
. These data should identifyparticipation.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
participation.
11.4
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
11.4
UCB reserves the right to temporaril
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
UCB reserves the right to temporaril
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 31 of 38
If the study is prematurely terminated or suspended, UCB (or its representative) will inform the Investigators/institutions and the regulatory authority(ies) of the termination or suspension and the reason(s) for the termination or suspension, in accordance with applicable regulatory requirement(s). The IRB should also be informed and provided with reason(s) for the termination or suspension by the sponsor or by the Investigator/institution, as specified by the applicable regulatory requirement(s). In addition, arrangements will be made for the return of the Kinesia devices and other material in accordance with UCB procedures for the study.
11.5 Archiving and data retention
The Investigator will maintain adequate records for the study, including eCRFs, medical records, Informed Consent documents, device dispensing and disposition records, safety reports, information regarding participants who discontinued, device distribution, and other pertinent data.
All essential documents are to be retained by the Investigator for at least 5 years after the final study report or first publication of the study results becomes available, whichever comes later. These documents should be retained for a longer period, however, if required by the applicable regulatory requirement(s) or by an agreement with UCB. The Investigator will contact UCB for authorization prior to the destruction of any study records or in the event of accidental loss or destruction of any study records. The Investigator will also notify UCB should he/she relocate or move the study-related files to a location other than that specified in the sponsor’s trial master file.
11.6 Audit and inspection
The Investigator will permit study-related audits mandated by UCB, after reasonable notice, and inspections by domestic or foreign regulatory authorities.
The main purposes of an audit or inspection are to confirm that the rights and well-being of the subjects enrolled have been protected, that enrolled subjects (ie, signing consent and undergoing study procedures) are appropriate for the study, and that all data relevant for the evaluation of Neupro have been processed and reported in compliance with the planned arrangements, the protocol, investigational site, and IRB SOPs, ICH-GCP, and applicable regulatory requirements.
The Investigator will provide direct access to all study documents, source records, and source data. If an inspection by a regulatory authority is announced, the Investigator will immediately inform UCB (or designee).
11.7 Good Clinical Practice
Noncompliance with the protocol, ICH-GCP, or local regulatory requirements by the Investigator, institution, institution staff, or designees of the sponsor will lead to prompt action by UCB to secure compliance. Continued noncompliance may result in the termination of the site’s involvement in the study.
12 STATISTICS
A description of statistical methods follows and will be described in more detail in the Statistical Analysis Plan (SAP).
REDACTED COPY nvestigator will also notify
REDACTED COPY nvestigator will also notify
s to a location other than that specified in the sponsor’s
REDACTED COPY
s to a location other than that specified in the sponsor’s
related audits mandated b
REDACTED COPY
related audits mandated b domestic or foreign regulatory
REDACTED COPY
domestic or foreign regulatory
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
CRFs, medical records,
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
CRFs, medical records, reports,
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
reports, and other pertinent
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
and other pertinent
for at least 5
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
for at least 5 ye
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
years after the final
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ars after the final y results becomes available, whichever comes later
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y results becomes available, whichever comes laterThese documents should be retained for a longer period, however, if required by
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
These documents should be retained for a longer period, however, if required bynvestigator will contact UCB for
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
nvestigator will contact UCB for y records or in the event of accidental loss or
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y records or in the event of accidental loss or nvestigator will also notify
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
nvestigator will also notifys to a location other than that specified in the sponsor’s
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
s to a location other than that specified in the sponsor’s
related audits mandated b
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
related audits mandated b domestic or foreign regulatory
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
domestic or foreign regulatory authorities.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
authorities. domestic or foreign regulatory authorities. domestic or foreign regulatory
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
domestic or foreign regulatory authorities. domestic or foreign regulatory
e main purposes of an audit or inspection are to confirm that the rights and well
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
e main purposes of an audit or inspection are to confirm that the rights and wellsubjects enrolled have been protected, that enrolled subjects (
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
subjects enrolled have been protected, that enrolled subjects ( procedures) are appropriate for the study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
procedures) are appropriate for the studyhave been processed and reported in compliance with the planned arrangements, the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
have been processed and reported in compliance with the planned arrangements, the protocol, investigational site, and I
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
protocol, investigational site, and I
Investigator will provide direct
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Investigator will provide direct data. If an inspection b
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
data. If an inspection by
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y a regulatory
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
a regulatoryinform UCB (or designee).
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
inform UCB (or designee).
Good Clinical Practice
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Good Clinical Practice
Noncompliance with the protocol, I
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Noncompliance with the protocol, Investigator, institution, institution staff, or designees of the sponsor will lead to prompt action
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
nvestigator, institution, institution staff, or designees of the sponsor will lead to prompt action by
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
by UCB to secure compliance. Continued noncompliance may
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
UCB to secure compliance. Continued noncompliance mayby UCB to secure compliance. Continued noncompliance mayby
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
by UCB to secure compliance. Continued noncompliance mayby
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
site’s involvement in the study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
site’s involvement in the study
12
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
12
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 32 of 38
12.1 Definition of analysis sets
Four analysis sets will be defined for this study: the Enrolled Set (ES), the Safety Set (SS), the Full Analysis Set (FAS), and the Per-Protocol Set (PPS).
The ES will consist of all subjects who signed the ICF.
The SS will consist of all subjects who received at least 1 dose of Neupro. The SS will be used for the analysis of all demographic, disposition, and safety data.
The FAS will consist of all subjects who have at least 1 valid Baseline and at least 1 valid post-Baseline efficacy measurement. The FAS will be used for the analysis and presentation of the efficacy data. In the case of misallocation, subjects will be primarily analyzed according to Kinesia-360 application (yes/no). However, if applicable, sensitivity analysis will also be performed according to the randomized group.
The PPS will consist of those subjects in the FAS who do not have any important protocol deviations that would have an impact on the efficacy variables. The PPS will be used for sensitivity analysis.
12.2 General statistical considerations
All analyses will be performed using SAS® version 9.3 or higher (SAS Institute, Cary, NC, USA). Continuous variables will be summarized by visit (where applicable) with the statistics including the number of subjects (n), mean, standard deviation (SD), median, minimum, and maximum. Categorical variables will be summarized by visit (where applicable) with frequency counts and percentages.
Unless otherwise specified, the comparisons will be for outcomes in subjects with Parkinson’s disease in the Experimental Group (optimal Neupro dosing regimen will be titrated using motor symptom data collected with the Kinesia-360 wearable technology in addition to standard clinical practice) versus outcomes in subjects with Parkinson’s disease in the Control Group (optimal Neupro dosing regimen will be titrated using only standard clinical practice). It is obvious that Kinesia-360 based efficacy data will be presented for the Experimental group only.
Unless otherwise specified, the level of significance for all tests will be 0.05. All statistical tests are 2-sided; however, they are exploratory only and p-values <0.05 do not indicate statistical significance, since no alpha adjustment will be performed.
All data recorded in the eCRF, APP, and questionnaires will be listed.
12.3 Planned efficacy analyses
12.3.1 Analysis of the efficacy variables
The efficacy variables, change from Baseline to Visit 2 (for all efficacy variables not based on Kinesia-360) will be analyzed utilizing an analysis of covariance (ANCOVA) with Baseline as a covariate, “center” as factor, and “group” as main factor. The 2 groups are the Experimental Group (EG) and the Control Group (CG).
The 2-sided null and alternative hypotheses are:
Null hypothesis (H0): EG=CG
Alternative hypothesis (Ha): EG≠CG
REDACTED COPY version 9.3 or
REDACTED COPY version 9.3 or
USA). Continuous variables will be summarized by visit (where applicable) with the statistics
REDACTED COPY
USA). Continuous variables will be summarized by visit (where applicable) with the statistics including the number of subjects (n), mean, standard deviation (SD), median, minimum, and
REDACTED COPY
including the number of subjects (n), mean, standard deviation (SD), median, minimum, and maximum. Categorical variables will be summarized by
REDACTED COPY
maximum. Categorical variables will be summarized by
Unless otherwise specified, the comparisons will be for outcomes in subjects with Parkinson’s
REDACTED COPY
Unless otherwise specified, the comparisons will be for outcomes in subjects with Parkinson’s disease in the Experimental Group (optimal NeuproREDACTED C
OPY
disease in the Experimental Group (optimal Neupromptom data collected with the Kinesia
REDACTED COPY
mptom data collected with the Kinesia
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
is and presentation of
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
is and presentation of zed according to
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
zed according to sis will also be
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
sis will also be
important protocol
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
important protocol PPS
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
PPS will be used for
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
will be used for
higher
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
higher (SAS Institute, Cary
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
(SAS Institute, CaryUSA). Continuous variables will be summarized by visit (where applicable) with the statistics
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
USA). Continuous variables will be summarized by visit (where applicable) with the statistics including the number of subjects (n), mean, standard deviation (SD), median, minimum, and
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
including the number of subjects (n), mean, standard deviation (SD), median, minimum, and maximum. Categorical variables will be summarized by
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
maximum. Categorical variables will be summarized by visit (where ap
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
visit (where apmaximum. Categorical variables will be summarized by visit (where apmaximum. Categorical variables will be summarized by
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
maximum. Categorical variables will be summarized by visit (where apmaximum. Categorical variables will be summarized by
Unless otherwise specified, the comparisons will be for outcomes in subjects with Parkinson’s
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Unless otherwise specified, the comparisons will be for outcomes in subjects with Parkinson’s disease in the Experimental Group (optimal Neupro
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
disease in the Experimental Group (optimal Neupromptom data collected with the Kinesia
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
mptom data collected with the Kinesia
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
-
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
-360 wearable technology
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
360 wearable technologyclinical practice) versus outcomes in subjects with Parkinson’s disease in the Control Group
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
clinical practice) versus outcomes in subjects with Parkinson’s disease in the Control Group (optimal Neupro dosing regimen will be titrated using onl
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
(optimal Neupro dosing regimen will be titrated using onl360 based efficacy
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
360 based efficacy
Unless otherwise specified, the level of significance for all tests will be 0.05. All statistica
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Unless otherwise specified, the level of significance for all tests will be 0.05. All statisticahowever, they
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
however, they are exploratory
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
are exploratoryhowever, they are exploratoryhowever, they
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
however, they are exploratoryhowever, they
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
significance, since no alpha
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
significance, since no alpha
All data recorded in the eCRF
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
All data recorded in the eCRF
Planned efficacy
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Planned efficacy
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
The efficacy
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
The efficacyKinesia
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Kinesiacovariate
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
covariate
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 33 of 38
EG: Represents the change from Baseline to Visit 2 for subjects in the Experimental Group.
CG: Represents the change from Baseline to Visit 2 for subjects in the Control Group.
The efficacy analysis will be performed on the FAS and observed cases will be utilized. The group effect will be estimated and presented with 95% 2-sided confidence intervals (CIs) and p-values.
The PPS will be used for sensitivity analysis on selected efficacy variables.
12.3.2 Other efficacy analyses
Kinesia-360-based efficacy data will be presented descriptively for the Experimental Group. Due to repeated measurements (during titration weekly and during maintenance), comparisons will be performed by time point and also by dose, if applicable (dependent on number of subjects in respective dose groups). Optional time points might also be subject to analysis (dependent on number of subjects at respective time points or windows for time points).
12.4 Planned safety analyses
12.4.1 Safety analyses
All analyses of safety data will be performed on the SS.
The incidence of subjects with treatment-emergent AEs (TEAEs) and/or SAEs will be determined. Furthermore, the absolute and relative frequencies for subjects with a given TEAE with respect to the preferred term according to the latest available version of the Medical Dictionary for Regulatory Activities (MedDRA®) will be determined within each study part and system organ class. Additional tables will include, but are not limited to, summaries of TEAEs by maximum event intensity and causal relationship to Neupro. The actions taken for each AE, the time of onset of the AE, and the duration of each AE will be listed.
Further details will be provided in the SAP.
12.5 Handling of protocol deviations
Important protocol deviations are identified as part of the data cleaning process in the Data Cleaning Plan. Ongoing data cleaning meetings will be held throughout the duration of the study. Objectives of these meetings include to review and update (if necessary) the important protocol deviations and discuss exclusion of subjects from analysis populations. Furthermore, overall trends in protocol deviations will be discussed at the Data Evaluation Meeting. Through this ongoing data cleaning and evaluation process, all decisions regarding important protocol deviations and exclusions from analysis populations are made on an ongoing basis.
12.6 Handling of dropouts or missing data
In general, there will be no imputation of missing data.
12.7 Planned interim analysis and data monitoring
Not applicable.
REDACTED COPY emergent AEs (TEAEs) and/or SAEs will be
REDACTED COPY emergent AEs (TEAEs) and/or SAEs will be
determined. Furthermore, the absolute and relative frequencies for subjects with a given TEAE
REDACTED COPY
determined. Furthermore, the absolute and relative frequencies for subjects with a given TEAE according to the latest available version of the Medical
REDACTED COPY
according to the latest available version of the Medical (MedDRA
REDACTED COPY
(MedDRA®
REDACTED COPY
®
tables will include, but are not limited to, summarie
REDACTED COPY
tables will include, but are not limited to, summarie and causal relationship to Neupro. The actions taken for each
REDACTED COPY
and causal relationship to Neupro. The actions taken for eachthe time of onset of the AE, and the duration of each AE will be listed.REDACTED C
OPY
the time of onset of the AE, and the duration of each AE will be listed.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
the Experimental Group. Due
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
the Experimental Group. Due comparisons will be
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
comparisons will be y time point and also by dose, if applicable (dependent on number of subjects in
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y time point and also by dose, if applicable (dependent on number of subjects in ints might also be subject to analysis (dependent on
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ints might also be subject to analysis (dependent on
emergent AEs (TEAEs) and/or SAEs will be
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
emergent AEs (TEAEs) and/or SAEs will be determined. Furthermore, the absolute and relative frequencies for subjects with a given TEAE
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
determined. Furthermore, the absolute and relative frequencies for subjects with a given TEAE according to the latest available version of the Medical
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
according to the latest available version of the Medical ) will be determined within each stud
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
) will be determined within each studtables will include, but are not limited to, summarie
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
tables will include, but are not limited to, summarie and causal relationship to Neupro. The actions taken for each
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
and causal relationship to Neupro. The actions taken for eachthe time of onset of the AE, and the duration of each AE will be listed.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
the time of onset of the AE, and the duration of each AE will be listed.
Further details will be provided in the SAP.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Further details will be provided in the SAP.
Handling of protocol deviations
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Handling of protocol deviations
Important protocol deviations are identified as part of the data cleaning process in the Data
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Important protocol deviations are identified as part of the data cleaning process in the Data
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
g Plan. Ongoing data cleaning meetings will be held throughout the duration of the study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
g Plan. Ongoing data cleaning meetings will be held throughout the duration of the studyObjectives of these meetings include to review and update (if necessary
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Objectives of these meetings include to review and update (if necessarydeviations and discuss exclusion of subjects from anal
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
deviations and discuss exclusion of subjects from analtrends in protocol deviations will be discussed at the Data Evaluation Meeting. Through this
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
trends in protocol deviations will be discussed at the Data Evaluation Meeting. Through this ongoing data cleaning and evaluation process, all decisions regarding
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ongoing data cleaning and evaluation process, all decisions regardingdeviations and exclusions from anal
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
deviations and exclusions from anal
In general, there will be no imputation of missing data.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
In general, there will be no imputation of missing data.
12.7
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
12.7
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 34 of 38
12.8 Determination of sample size
Due to the character of the study, no formal sample size estimation can be performed. A sample size of approximately 40 will be regarded to be sufficient to get an impression of the effect of the device on the efficacy variables.
13 ETHICS AND REGULATORY REQUIREMENTS
13.1 Informed consent
Subject’s informed consent must be obtained and documented in accordance with local regulations, ICH-GCP requirements, and the ethical principles that have their origin in the principles of the Declaration of Helsinki.
Prior to obtaining informed consent, information should be given in a language and at a level of complexity understandable to the subject in both oral and written form by the Investigator (or designee). Each subject will have the opportunity to discuss the study and its alternatives with the Investigator.
Prior to participation in the study, the ICF should be signed and personally dated by the subject, or his/her legal representative, and by the person who conducted the informed consent discussion (Investigator or designee). The subject or his/her legal representative must receive a copy of the signed and dated ICF. As part of the consent process, each subject must consent to direct access to his/her medical records for study-related monitoring, auditing, IRB review, and regulatory inspection.
If the ICF is amended during the study, the Investigator (or the Sponsor, if applicable) must follow all applicable regulatory requirements pertaining to the approval of the amended ICF by the IRB and use of the amended form.
All studies conducted at centers in the US must include the use of a Health Insurance Portability and Accountability Act Authorization form.
The subject may withdraw his/her consent to participate in the study at any time. A subject is considered as enrolled in the study when he/she has signed the ICF. An eCRF must not be started, nor may any study specific procedure be performed for a given subject, without having obtained his/her written consent to participate in the study.
13.2 Subject identification cards
Upon signing the ICF, the subject or legal representative will be provided with a subject identification card in the language of the subject. The Investigator will fill in the subject identifying information and medical emergency contact information. The Investigator will instruct the subject to keep the card with him/her at all times.
13.3 Institutional Review Boards
The study will be conducted under the auspices of an IRB and in accordance with the ethical principles that have their origin in the Declaration of Helsinki.
The Investigator(s)/UCB will ensure that an appropriately constituted IRB that complies with applicable country-specific regulations will be responsible for the initial and continuing review and approval of the clinical study. Prior to initiation of the study, the Investigator/UCB will
REDACTED COPY ignee). The subject or his/her legal representative must receive a cop
REDACTED COPY ignee). The subject or his/her legal representative must receive a cop
As part of the consent process, each subject must consent to direct access
REDACTED COPY As part of the consent process, each subject must consent to direct access
-related monitoring, auditing, IRB review, a
REDACTED COPY
-related monitoring, auditing, IRB review, a
, the
REDACTED COPY
, the Investigator (or the Sponsor, if applicable) must
REDACTED COPY
Investigator (or the Sponsor, if applicable) must requirements pertaining to the approval of the amended I
REDACTED COPY
requirements pertaining to the approval of the amended IRB and use of the amended form.
REDACTED COPY
RB and use of the amended form.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
-GCP requirements, and the ethical principles that have their origin in the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
-GCP requirements, and the ethical principles that have their origin in the
taining informed consent, information should be given in a language and at a level of
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
taining informed consent, information should be given in a language and at a level of the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
the Investigator (or
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Investigator (or and
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
and its alternatives with
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
its alternatives with
should be signed and personally
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
should be signed and personallyy the person who conducted the informed consent discussion
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y the person who conducted the informed consent discussion ignee). The subject or his/her legal representative must receive a cop
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ignee). The subject or his/her legal representative must receive a copAs part of the consent process, each subject must consent to direct access
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
As part of the consent process, each subject must consent to direct access -related monitoring, auditing, IRB review, a
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
-related monitoring, auditing, IRB review, a
Investigator (or the Sponsor, if applicable) must
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Investigator (or the Sponsor, if applicable) must requirements pertaining to the approval of the amended I
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
requirements pertaining to the approval of the amended I
studies conducted at centers in the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
studies conducted at centers in the US
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
US must include the use of a Health Insurance Portability
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
must include the use of a Health Insurance Portability Act Authorization form.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Act Authorization form.
withdraw his/her consent to participate in the study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
withdraw his/her consent to participate in the studyn the study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
n the studyy study specific procedure be performed for a given subject, without having
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y study specific procedure be performed for a given subject, without having obtained his/her written consent to participate in the study.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
obtained his/her written consent to participate in the study.
Subject identification cards
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Subject identification cards
igning the I
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
igning the ICF
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
CFidentification card in the language of the subject. The Investigator will fill in the subject
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
identification card in the language of the subject. The Investigator will fill in the subject identify
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
identifying information and medical emergency
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ing information and medical emergencyinstruct the subject to keep the card with him/her at all times.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
instruct the subject to keep the card with him/her at all times.
13.3
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
13.3
Th
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Th
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 35 of 38
forward copies of the protocol, ICF, Investigator’s Brochure, Investigator’s curriculum vitae (if applicable), advertisement (if applicable), and all other subject-related documents to be used for the study to the IRB for its review and approval.
Before initiating a study, the Investigator will have written and dated full approval from the responsible IRB for the protocol and all other documents submitted to the IRB.
The Investigator will also promptly report to the IRB all changes in the study, all unanticipated problems involving risks to human subjects or others, and any protocol deviations, to eliminate immediate hazards to subjects.
The Investigator will not make any changes in the study or study conduct without IRB approval, except where necessary to eliminate apparent immediate hazards to the subjects. For minor changes to a previously approved protocol during the period covered by the original approval, it may be possible for the Investigator to obtain an expedited review by the IRB as allowed.
As part of the IRB requirements for continuing review of approved studies, the Investigator will be responsible for submitting periodic progress reports to the IRB (based on IRB requirements), at intervals appropriate to the degree of subject risk involved, but no less than once per year. The Investigator should provide a final report to the IRB following study completion.
UCB (or its representative) will communicate safety information to the appropriate regulatory authorities and all active Investigators in accordance with applicable regulatory requirements. The appropriate IRB will also be informed by the Investigator or the Sponsor, as specified by the applicable regulatory requirements in each concerned country. Where applicable, Investigators are to provide the Sponsor (or its representative) with evidence of such IRB notification.
13.4 Subject privacy
UCB staff (or designee) will affirm and uphold the subject’s confidentiality. Throughout this study, all data forwarded to UCB (or designee) will be identified only by the subject number assigned at Screening.
The Investigator agrees that representatives of UCB, its designee, representatives of the relevant IRB, or representatives of regulatory authorities will be allowed to review that portion of the subject’s primary medical records that directly concerns this study (including, but not limited to, admission/discharge summaries for hospital admissions occurring during a subject’s study participation, and autopsy reports for deaths occurring during the study).
13.5 Protocol amendments
Protocol changes may affect the legal and ethical status of the study and may also affect the statistical evaluations of sample size and the likelihood of the study fulfilling its primary objective.
Significant changes to the protocol will only be made as an amendment to the protocol and must be approved by UCB, the IRB, and the regulatory authorities (if required), prior to being implemented.
14 FINANCE, INSURANCE, AND PUBLICATION
Insurance coverage will be handled according to local requirements.
REDACTED COPY information to the appropriate regulatory
REDACTED COPY information to the appropriate regulatory
nvestigators in accordance with applicable regulatory
REDACTED COPY
nvestigators in accordance with applicable regulatoryy the
REDACTED COPY
y the I
REDACTED COPY
Investigator or the
REDACTED COPY
nvestigator or the
REDACTED COPY
requirements in each concerned country
REDACTED COPY
requirements in each concerned countrySponsor (or its representative) with evidence of such IRB notification.
REDACTED COPY
Sponsor (or its representative) with evidence of such IRB notification.
UCB staff (or designee) will affirm and uphold the subject’s confidentiality. Throughout this REDACTED COPY
UCB staff (or designee) will affirm and uphold the subject’s confidentiality. Throughout this
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y protocol deviations, to eliminate
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
y protocol deviations, to eliminate
B approval,
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
B approval, to eliminate apparent immediate hazards to the subjects. For minor
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
to eliminate apparent immediate hazards to the subjects. For minor the original approval, it
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
the original approval, it ed review by the IRB as allowed.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
ed review by the IRB as allowed.
As part of the IRB requirements for continuing review of approved studies, the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
As part of the IRB requirements for continuing review of approved studies, the RB (based on I
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
RB (based on Ie degree of subject risk involved, but no less than once per
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
e degree of subject risk involved, but no less than once per nvestigator should provide a final report to the IRB following study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
nvestigator should provide a final report to the IRB following study completion.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
completion.nvestigator should provide a final report to the IRB following study completion.nvestigator should provide a final report to the IRB following study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
nvestigator should provide a final report to the IRB following study completion.nvestigator should provide a final report to the IRB following study
information to the appropriate regulatory
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
information to the appropriate regulatorynvestigators in accordance with applicable regulatory
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
nvestigators in accordance with applicable regulatorynvestigator or the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
nvestigator or the
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
requirements in each concerned country
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
requirements in each concerned countrySponsor (or its representative) with evidence of such IRB notification.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Sponsor (or its representative) with evidence of such IRB notification.
UCB staff (or designee) will affirm and uphold the subject’s confidentiality. Throughout this
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
UCB staff (or designee) will affirm and uphold the subject’s confidentiality. Throughout this , all data forwarded to UCB (or designee) will be identified only
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
, all data forwarded to UCB (or designee) will be identified only
Investigator agrees that representatives of UCB, its designee, representatives of the relevant
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Investigator agrees that representatives of UCB, its designee, representatives of the relevant B, or representatives of regulatory
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
B, or representatives of regulatory medical records that directl
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
medical records that directladmission/discharge summaries for hospital admissions occurring during a subject’s study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
admission/discharge summaries for hospital admissions occurring during a subject’s study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
participation, and autopsy
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
participation, and autopsy
Protocol amendments
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Protocol amendments
Protocol changes may affect the legal and ethical status of the study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Protocol changes may affect the legal and ethical status of the studystatistical evaluations of sample size and the likelihood of the study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
statistical evaluations of sample size and the likelihood of the study
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
objective.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
objective.
Signif
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Signifbe approved b
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
be approved b
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 36 of 38
Finance, insurance, and publication rights are addressed in the Investigator and/or CRO agreements, as applicable.
15 REFERENCES
NEUPRO [package insert]. Smyrna, GA: UCB Inc.; 2016
REDACTED COPY
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 37 of 38
16 DECLARATION AND SIGNATURE OF INVESTIGATOR
I confirm that I have carefully read and understood this protocol and agree to conduct this clinical study as outlined in this protocol, according to current Good Clinical Practice and local laws and requirements.
I will ensure that all subinvestigators and other staff members read and understand all aspects of this protocol.
I have received and read all study-related information provided to me.
The objectives and content of this protocol as well as the results deriving from it will be treated confidentially, and will not be made available to third parties without prior authorization by UCB.
All rights of publication of the results reside with UCB, unless other agreements were made in a separate contract.
Investigator:
Printed name Date/Signature
REDACTED COPY
Date/Signature
REDACTED COPY
Date/Signature
REDACTED COPY
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
The objectives and content of this protocol as well as the results deriving from it will be treated
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
The objectives and content of this protocol as well as the results deriving from it will be treated , and will not be made available to third parties without prior authorization by
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
, and will not be made available to third parties without prior authorization by
All rights of publication of the results reside with UCB, unless other agreements were made in a
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
All rights of publication of the results reside with UCB, unless other agreements were made in a
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Date/Signature
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
Date/Signature
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
UCB 16 Dec 2016Clinical Study Protocol Rotigotine transdermal system PD0049
Confidential Page 38 of 38
17 SPONSOR DECLARATION
I confirm that I have carefully read and understand this protocol and agree to conduct this clinical study as outlined in this protocol and according to current Good Clinical Practice.
REDACTED COPY
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
REDACTED COPY
REDACTED COPY
REDACTED COPY
REDACTED COPY
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
This do
cumen
t can
not b
e use
d to s
uppo
rt any
mark
eting
autho
rizati
on ap
plica
tion a
nd an
y exte
nsion
s or v
ariati
ons t
hereo
f.
