2013q1 Susar Liraglutide Published

Global Quality, Global Safety

CONFIDENTIAL

Date: 25 April 2013 Novo Nordisk

Safety Surveillance Diabetes Version: 1.0

Periodic SUSAR Report Status: Final

Liraglutide, Q1 2013 Page: 1 of 5

Periodic Suspected Unexpected Serious Adverse Reactions (SUSAR) Report

Liraglutide

Q1 2013

(includes blinded trial data)

Confidentiality Statement:

This report may include unblinded adverse event data. This document is a confidential

communication from Novo Nordisk A/S. This document may only be disclosed to duly authorised

representatives of regulatory authorities, as appropriate, under the condition that it is confidential.

No information contained herein may be disclosed without prior written approval from Novo

Nordisk A/S.

Author

Jannik Nielsen

Safety Surveillance Diabetes, Non-Insulin


CONFIDENTIAL





Table of contents

Page

Table of contents...............................................................................................................................................2

Table of tables...................................................................................................................................................2

1 Introduction...............................................................................................................................................3

2 Line listings ................................................................................................................................................3

3 Safety statement ........................................................................................................................................3

3.1 EX2211-3748 LEADER.............................................................................................................4

3.2 Development programme NN8022 (SCALE) ............................................................................4

3.3 Development programme NN2211................................................................................................5

3.4 Overall safety statement.................................................................................................................5

Appendix 1: Line listing of all suspected unexpected serious adverse reactions from the review

period

Table of tables

Page

Table 1 Distribution of SUSAR events in EX2211-3748 LEADER

........................................................4

Table 2 Distribution of SUSAR events in NN8022 (SCALE)..................................................................5

Table 3 Distribution of SUSAR events in NN2211....................................................................................5


CONFIDENTIAL





1 Introduction

This periodic safety report is made according to the requirements in the EU clinical trials directive

(Directive 2001/20/EC, 4 April 2001) and Detailed guidance on the collection, verification and

presentation of adverse reaction reports arising from clinical trials on medicinal products for human

use, (CT-3) (2011/C 172/01) and includes line listings of suspected unexpected serious adverse

reactions (SUSARs) and a safety statement. The investigators are continuously informed of

individual cases qualifying as SUSARs. This periodic SUSAR report aggregates the individual

SUSARs reported during Q1 2013. The purpose of this information obligation towards the

investigator is to inform investigators of safety issues in view of detected SUSARs for liraglutide

during Q1 2013.

2 Line listings

The attached line listings presents all SUSARs reported from clinical trials in connection with the

use of liraglutide received by Global Safety, Novo Nordisk A/S in the period 01 Jan 2013 31 Mar

2013. The SUSARs are from all worldwide Novo Nordisk-sponsored clinical trials, where

liraglutide has been used as primary investigational drug. The line listings include

placebo/comparator cases and the data is presented blinded to treatment allocation.

For the development project NN8022 expectedness is evaluated in accordance with current version

of the investigator brochure (IB). For the post-marketing trial EX2211-3748 and all NN2211 trials

Expectedness is evaluated in accordance with the current version of the company core data sheet

(CCDS). It should be noted that expectedness/listedness of a serious adverse drug reaction may

have changed in the period from when it was reported as an expedited report and until this Periodic

SUSAR Report.

The SUSARs have been recorded in the Novo Nordisk A/S global safety database.

Reports from clinical trials are considered to have a causal relationship between the trial product

and the event if assessed possible/probable related by the reporter and/or Novo Nordisk A/S.

All events have been coded by use of MedDRA (Medical Dictionary for Regulatory Activities).

3 Safety statement

During the reporting period, 39 reports including 48 SUSAR events have been received in

connection with the use of liraglutide.


CONFIDENTIAL





3.1 EX2211-3748 LEADER

In EX2211-3748 (liraglutide in T2DM patients with high cardiovascular risk), 28 SUSAR reports

including 37 SUSARs were received during the reporting period. Table 1 lists the SUSARs

categorised by medical area of interest. The most frequently reported SUSARs were from the

System Organ Class Cardiovascular disorders, which the trial population is at high risk of

developing. Additional reports were observed within the categories of hepatobiliary disorders and

pancreatitis. A total of 1 case (with 2 SUSARs) had fatal outcome; the preferred terms of the fatal

case were: Hepatic cancer metastatic and Abdominal pain.

Table 1 Distribution of SUSAR events in EX2211-3748 LEADER

SUSARs Total

Cardiovascular disorders* 18

Pancreatitis# 2

Hepatobiliary disorders 2

Neoplasms benign, malignant and unspecified

(incl cysts and polyps)

6

Other 9

Grand total 37

The SUSARs are identified by: *MedDRA SMQs: Ischaemic heart disease, Cardiac arrhythmias, Cardiomyopathy,

Cardiac failure, Embolic and thrombotic events, Shock, Torsade de pointes/QT prolongation, Cerebrovascular

disorders and Vasculitis, #MedDRA SMQ Acute Pancreatitis and SOC Hepatobiliary Disorders and

Neoplasms benign, malignant and unspecified (incl cysts and polyps), respectively

The frequency and distribution of the SUSARs does not cause a safety concern in this trial with

more than 9.000 patients randomised. The next meeting in the Data Monitoring Committee will be

held on 17 May 2013.

3.2 Development programme NN8022 (SCALE)

In the NN8022 development programme (liraglutide in obesity), 7 reports including 8 SUSAR

events were received during the reporting period. One report (1 SUSAR) had fatal outcome, which

included the event: Ventricular fibrillation. Table 2 lists the SUSARs by medical area of interest.


CONFIDENTIAL





Table 2 Distribution of SUSAR events in NN8022 (SCALE)

SUSAR Total

Hepatobiliary disorders* 3

Investigations* 2

Other 3

Grand total 8

The SUSARs are identified by: *SOC

The frequency and distribution of the SUSARs does not cause a safety concern due to the low

number and type of reports.

3.3 Development programme NN2211

From the NN2211 development program (liraglutide in T2DM), 3 reports including 3 SUSARs

were received during the reporting period. Two SUSAR from NN2211-3916, and one from

NN2211-3924. None of the cases were fatal. Table 3 lists the SUSARs medically area of interest.

Table 3 Distribution of SUSAR events in NN2211

SUSARs Total

Infections and infestations* 1

Vascular disorders* 1

Neoplasms benign, malignant and unspecified

(incl cysts and polyps)*

1

Grand total 3

The SUSARs are identified by: *SOC

The frequency and distribution of the SUSARs does not cause a safety concern.

3.4 Overall safety statement

Overall, based on the reported SUSARs in the period covered by this report, there is no indication

of significant changes to the evolving safety profile of liraglutide. The information does not give

rise to safety concerns that would warrant update of the current safety information in either the

current version of the investigator brochure (IB) for the development project, or the CCDS of

Victoza.

Date: 18-Apr-2013 06:52:33 2013 Q1 SUSAR Liraglutide BlindedReport #: Period: 01-Jan-2013 Through 31-Mar-2013

Ingredient: liraglutide, Placebo

Case NumberCountrySource

AgeSex

Product Name / FormDaily Dose[Dose Frequency] Route

Dates ofTreatment orTreatmentDuration

Event Onset Dateor Time to Onset

Event Verbatim[Preferred Term]Ser/UL/Causal

PatientOutcome

3 Unlocked Case. * SUSAR Event.

Page 1 of 6

Study ID: EX2211-3748 (29)368132 TURKEY

Clinical Trial70 YearsMale

Blinded Liraglutide vs. Placebo / BlindedBlinded

Blinded 04-NOV-2011 Ongoing

14-DEC-2012 Not defined mass in the lung [PULMONARY MASS]*Y / Y / Y

Not recovered

Study ID: EX2211-3748368531 FINLAND



Blinded 10-JAN-2012 Ongoing02-JAN-2013 Ventricular tachycardia [VENTRICULAR TACHYCARDIA]*Y / Y / Y

Recovered

Study ID: EX2211-3748368856 UNITED

STATESClinical Trial

68 YearsMale


Blinded 08-JUL-2011 Ongoing 21-NOV-2012 Unstable angina [ANGINA UNSTABLE]*Y / Y / Y

Recovered



68 YearsFemale


Blinded 01-MAR-2012 to 24-DEC-2012

25-DEC-2012 Right transient ischemic attack [TRANSIENT ISCHAEMIC ATTACK]*Y / Y / Y

Recovered



75 YearsMale


Blinded 16-FEB-2012 to 01-JAN-2013

Blinded Blinded 22-JAN-2013 Ongoing

01-JAN-2013 Myocardial Infarction [MYOCARDIAL INFARCTION]*Y / Y / Y

Recovered

Study ID: EX2211-3748369729 INDIA



Blinded 10-AUG-2011 to 26-JAN-2013

14-JAN-2013 Acute Cholecystitis [CHOLECYSTITIS ACUTE]*Y / Y / Y

Recovered

Study ID: EX2211-3748369862 CANADA



Blinded 01-DEC-2011 to 26-JAN-2013


17-JAN-2013 Intermittent Chest pain; not yest diagnosed (NYD) [CHEST PAIN]*Y / Y / Y

Not recovered



60 YearsMale


Blinded 02-DEC-2011 to 25-JAN-2013

Blinded Blinded 04-FEB-2013 Ongoing

28-JAN-2013 Non-ST-elevation myocardial infarction which was shown by EKG [ACUTE MYOCARDIAL INFARCTION]*Y / Y / Y

Recovered


KINGDOMClinical Trial

70 YearsMale


Blinded 20-FEB-2012 Ongoing

25-JAN-2013 Angina pectoris [ANGINA PECTORIS]*Y / Y / Y

Recovered

Study ID: EX2211-3748



AgeSex





PatientOutcome


Page 2 of 6

370871 UNITED STATESClinical Trial

64 YearsFemale


Blinded 05-JAN-2011 to 07-FEB-2013

08-JAN-2013 Acute Pancreatitis [PANCREATITIS ACUTE]*Y / Y / Y

Recovered



71 YearsMale


Blinded 09-JUN-2011 to 01-NOV-2012

08-FEB-2013 Obstructing Terminal Ileum Crohns disease [SMALL INTESTINAL OBSTRUCTION]*Y / Y / Y

Not recovered

Study ID: EX2211-3748371914 TURKEY



Blinded 19-JAN-2012 to 25-JAN-2013


24-JAN-2013 ibs (irritable bowel syndrome) [IRRITABLE BOWEL SYNDROME]*Y / Y / Y

Recovered

Study ID: EX2211-37483 371924 FRANCE



Blinded 31-MAY-2011 Ongoing

12-FEB-2013 Worsening of adenocarcinoma of colon [COLON CANCER]*Y / Y / Y

Not recovered

Study ID: EX2211-37483 371955 UNITED


61 YearsFemale


Blinded 21-OCT-2012 to 20-FEB-2013

20-FEB-2013 hyperkalemia [HYPERKALAEMIA]*Y / Y / Y

Recovered

20-FEB-2013 Acute renal failure [RENAL FAILURE ACUTE]Y / N / Y



73 YearsMale


Blinded 07-DEC-2010 to Unknown

18-NOV-2012 Multifocal Hepatocellular Carcinoma Metastatic [HEPATIC NEOPLASM MALIGNANT]*Y / Y / Y

Not recovered

18-JAN-2013 Lung metastases [METASTASES TO LUNG]*Y / Y / Y

18-JAN-2013 Bone metastisies [METASTASES TO BONE]*Y / Y / Y



65 YearsMale


Blinded 09-MAR-2012 to 15-JAN-2013

14-JAN-2013 Metastatic hepatocellular carcinoma [HEPATIC CANCER METASTATIC]*Y / Y / Y

Fatal

07-MAR-2013 Hospital admission for abdominal pain [ABDOMINAL PAIN]*Y / Y / Y

Study ID: EX2211-37483 372221 CZECH

REPUBLICClinical Trial

66 YearsMale


Blinded 16-NOV-2011 to 28-FEB-2013

28-FEB-2013 Coronary revascularization procedure [CORONARY REVASCULARISATION]*Y / Y / Y

Recovered

28-FEB-2013 Acute coronary syndrome with ST elevations [ACUTE CORONARY SYNDROME]*Y / Y / Y



AgeSex





PatientOutcome


Page 3 of 6

12-MAR-2013 Coronary revascularization procedure [CORONARY REVASCULARISATION]*Y / Y / Y

Study ID: EX2211-37483 372591 CANADA



Blinded 12-MAR-2012 to Unknown

26-FEB-2013 Hospitalization non-cardiac chest pain [NON-CARDIAC CHEST PAIN]*Y / Y / Y

Recovered

Study ID: EX2211-37483 372843 SPAIN

Clinical Trial81 YearsFemale


Blinded 24-FEB-2011 to 02-MAR-2013

Blinded Blinded 20-MAR-2013 Ongoing

02-MAR-2013 Cholecystitis [CHOLECYSTITIS]*Y / Y / Y

Not recovered



54 YearsFemale


Blinded 08-MAR-2012 Ongoing

20-JAN-2013 Chest pain [CHEST PAIN]*Y / Y / Y

Recovered

Study ID: EX2211-3748373022 AUSTRALIA



Blinded 22-FEB-2012 Ongoing

25-FEB-2013 Elective coronary artery stenting [CORONARY ARTERIAL STENT INSERTION]*Y / Y / Y

Recovered

25-FEB-2013 Worsening angina pectoris [ANGINA PECTORIS]*Y / Y / Y



55 YearsFemale


Blinded 11-MAR-2011 to 20-FEB-2013

Blinded Blinded 27-FEB-2013 Ongoing

20-FEB-2013 Acute gastroenteritis [GASTROENTERITIS]*Y / Y / Y

Recovered

Study ID: EX2211-3748373189 TURKEY



Blinded 03-FEB-2011 to 28-FEB-2013


28-FEB-2013 Unstabil angina [ANGINA UNSTABLE]*Y / Y / Y

Recovered

05-MAR-2013 Coronary artery stenting [CORONARY ARTERIAL STENT INSERTION]*Y / Y / Y

Study ID: EX2211-37483 373608 UNITED


70 YearsMale


Blinded 26-DEC-2012 to Unknown

Blinded Blinded 14-NOV-2011 to 01-DEC-2012

08-DEC-2012 Retroperitoneal mass [RETROPERITONEAL MASS]*Y / Y / Y

Not recovered

Study ID: EX2211-3748



AgeSex





PatientOutcome


Page 4 of 6

3 373616 UNITED STATESClinical Trial

70 YearsMale


Blinded 14-NOV-2011 to 01-DEC-2012

Blinded Blinded 26-DEC-2012 to Unknown

06-DEC-2012 Acute diastolic heart failure [CARDIAC FAILURE ACUTE]*Y / Y / Y

Not recovered

Study ID: EX2211-3748373690 GERMANY



Blinded 12-MAR-2012 to 18-MAR-2013

11-MAR-2013 Small-celled bronchial carcinoma [BRONCHIAL CARCINOMA]*Y / Y / Y

Not recovered

Study ID: EX2211-3748373931 BRAZIL



Blinded 12-AUG-2012 to 03-MAR-2013


03-MAR-2013 Acute myocardial infarction [ACUTE MYOCARDIAL INFARCTION]*Y / Y / Y

Recovered

Study ID: EX2211-3748373932 GERMANY



Blinded 01-MAR-2012 to 20-MAR-2013

18-MAR-2013 pancreatitis [PANCREATITIS]*Y / Y / Y

Not recovered

21-MAR-2013 Suspicion of pancreatic cyst [PANCREATIC CYST]*Y / Y / Y



80 YearsMale


Blinded 06-SEP-2011 Ongoing

15-AUG-2012 Myocardial Infarction [MYOCARDIAL INFARCTION]*Y / Y / Y

Not Reported

Study ID: EX2211-3748Study ID: NN2211-3916 (2)

369226 RUSSIAN FEDERATIONClinical Trial

71 YearsMale

Blinded Liraglutide as add-on to existing diabetes medication / BlindedBlinded

Blinded 17-SEP-2012 to 28-JAN-2013

11-JAN-2013 Impairment of blood circulation of 1st finger of a foot [POOR PERIPHERAL CIRCULATION]*Y / Y / Y

Recovered

Study ID: NN2211-3916370867 RUSSIAN

FEDERATIONClinical Trial

66 YearsMale

Blinded Liraglutide as add-on to existing diabetes medication / BlindedBlinded

Blinded 20-SEP-2012 to 10-FEB-2013

05-FEB-2013 osteomyelitis of 5 plantar bone of right foot [OSTEOMYELITIS]*Y / Y / Y

Recovering/resolving

Study ID: NN2211-3916Study ID: NN2211-3924 (1)

369709 JAPANClinical Trial

81 YearsMale

Liraglutide FlexPen / Solution for injection.9 mg [.9 mg-qd]

Subcutaneous 28-JAN-2012 to 25-JAN-2013

25-JAN-2013 Pulmonary cancer (stage II) [LUNG CARCINOMA CELL TYPE UNSPECIFIED STAGE II]*Y / Y / Y

Not recovered

Study ID: NN2211-3924



AgeSex





PatientOutcome


Page 5 of 6

Study ID: NN8022-1839 (6)368323 DENMARK


Blinded Liraglutide vs. placebo / BlindedBlinded

Blinded 21-JUL-2011 to Unknown

Blinded Blinded 18-AUG-2011 Ongoing

01-AUG-2012 Acute cholecystitis [CHOLECYSTITIS ACUTE]*Y / Y / Y

Recovered

01-AUG-2012 Gallstone [CHOLELITHIASIS]*Y / Y / Y

Study ID: NN8022-1839370014 IRELAND



Blinded 11-AUG-2011 to 21-AUG-2011

24-APR-2012 Chronic cholecystitis [CHOLECYSTITIS CHRONIC]*Y / Y / Y

Recovered

Study ID: NN8022-1839371416 SOUTH AFRICA




Blinded Blinded AUG-2011 to 06-SEP-2012

04-SEP-2012 Elevated lipase [LIPASE INCREASED]*Y / Y / Y

Recovered

Study ID: NN8022-1839372452 SWITZERLAND



Blinded 27-AUG-2011 to Unknown

Blinded Blinded 23-SEP-2011 to 28-FEB-2013

21-FEB-2013 Invasive ductal mamma carcinoma left breast [BREAST CANCER]*Y / Y / Y

Not recovered

Study ID: NN8022-1839372534 POLAND




Blinded Blinded 01-SEP-2011 Ongoing

11-JAN-2013 Elevated lipase [LIPASE INCREASED]*Y / Y / Y

Recovered

Study ID: NN8022-1839374290 UNITED


67 YearsMale


Blinded 24-AUG-2011 to Unknown

Blinded Blinded 21-SEP-2011 to 23-MAR-2013

24-MAR-2013 1. Acute cardiopulmonary arrest, 2. Ventricular fibrillation [VENTRICULAR FIBRILLATION]*Y / Y / Y

Fatal

Study ID: NN8022-1839Study ID: NN8022-3970 (1)

368580 UNITED STATESClinical Trial

61 YearsMale

Blinded Liraglutide for Sleep Apnoea / BlindedBlinded

Blinded 06-SEP-2012 to Unknown

Blinded Blinded 04-OCT-2012 to 01-DEC-2012

21-SEP-2012 Worsening of Vivid dreams with extreme violence [NIGHTMARE]*Y / Y / Y

Recovered

Study ID: NN8022-3970



AgeSex





PatientOutcome


Page 6 of 6

Total number of case entries printed: 39Total number of cases printed: 39

SUSAR Q1 2013Table of contentsTable of tables1 Introduction2 Line listings3 Safety statement3.1 EX2211-3748 LEADER3.2 Development programme NN8022 (SCALE)3.3 Development programme NN22113.4 Overall safety statement

Appendix 1: Line listing of all suspected unexpected serious adverse reactions from the review period

2013q1 Susar Liraglutide Published

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