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CLINICAL STUDY PROTOCOL

TITLE: Does a transdermal magnesium oil spray correct a low serum

magnesium in patients with a small bowel stoma

PHASE: Phase 2

STUDY PRODUCT: Magnesium oil spray (Magnesium Chloride)

SPONSOR: BetterYou LTD

Unit 5 Chambers Way

Thorncliffe, Chapel Town,

Sheffield, S35 2PH. UK

Telephone: 01142202229

Email: andy@betteryou.uk.com

CHIEF INVESTIGATOR: Dr Jeremy Nightingale MBBS MD FRCP

Northwest London NHS Hospital

Watford Road

London, HA1 3UJ. UK.

Telephone: 02082354038

Email: Jeremy.nightingale@nhs.net

CO-INVESTIGATORS: Mr Franklin Adaba MBBS MRCS

Northwest London NHS Hospital

Watford Road, London. HA1 3UJ. UK

Email: f.adaba@nhs.net

Dr Kinesh Patel MBBS MRCP

Northwest London NHS Hospital

Watford Road, London. HA1 3UJ. UK

Email: kineshpatel@nhs.net

STUDY SITE: Northwest London NHS Hospital

Watford Road

London, HA1 3UJ. UK.

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PROTOCOL APPROVAL SIGNATURES

Sponsor’s Approval

This protocol has been approved by BetterYou Ltd

Name: Title Role:

Signature: Date:

Chief Investigator’s Approval

I have read this protocol for the transdermal oil spray study. I have fully discussed the objectives

of this trial and the contents of this protocol with the sponsor (BetterYou Ltd). I agree to condut

this study according to the protocol and to comply with its requirements subject to ethical and

safety considerations and guidelines and to conduct the study in accordance with the

International Conference on Harmonisation (ICH) guidelines on Good Clinical Practice (GCP)

and with the applicable regulatory requirements.

Name: Title Role:

Signature: Date:

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1Table of Contents

STUDY SUMMARY ................................................................................................................................................... 1

1 INTRODUCTION .............................................................................................................................................. 2

1.1 RATIONAL FOR STUDY ........................................................................ ERROR! BOOKMARK NOT DEFINED. 1.2 INVESTIGATIONAL PRODUCT ............................................................... ERROR! BOOKMARK NOT DEFINED. 1.3 POTENTIAL BENEFIT ............................................................................ ERROR! BOOKMARK NOT DEFINED. 1.4 POTENTIAL RISK .................................................................................. ERROR! BOOKMARK NOT DEFINED.

2 STUDY OBJECTIVES ...................................................................................................................................... 3

3 STUDY DESIGN ................................................................................................................................................ 3

3.1 STUDY FLOW CHART .................................................................................................................................... 4 3.2 PRIMARY STUDY ENDPOINTS ...................................................................................................................... 4 3.3 SECONDARY STUDY ENDPOINTS ................................................................................................................. 4

4 SUBJECT SELECTION AND WITHDRAWAL............................................................................................ 5

4.1 INCLUSION CRITERIA ................................................................................................................................... 5 4.2 EXCLUSION CRITERIA ................................................................................................................................. 5 4.3 SUBJECT RECRUITMENT AND SCREENING ................................................................................................... 5 4.4 EARLY WITHDRAWAL OF SUBJECTS ............................................................................................................ 6

4.5 PARTICIPANTS FOLLOW UP .......................................................................................................................... 6

4.6 DATA COLLECTION AND FOLLOW UP OF WITHDRAWN PARTICIPANTS………………………………………………..6

5 STUDY PRODUCT ........................................................................................................................................... 7

5.1 DESCRIPTION ............................................................................................................................................... 7 5.2 TREATMENT REGIMEN ................................................................................................................................ 7 5.3 PREPARATION AND ADMINISTRATION OF STUDY PRODUCT ......................................................................... 7 5.4 PARTICIPANT COMPLIANCE MONITORING .............................................................................................. 7 5.5 RECEIVING, STORAGE, DISPENSING AND RETURN ....................................................................................... 7

5.5.1 Receipt of Study Product supplies .......................................................................................................... 7 5.5.2 Storage ................................................................................................................................................... 7 5.5.3 Dispensing of Study Product .................................................................................................................. 8

6 STATISTICAL PLAN ....................................................................................................................................... 8

6.1 SAMPLE SIZE DETERMINATION ................................................................................................................... 8 6.2 STATISTICAL METHODS............................................................................................................................... 8

6.3 SUBJECT POPULATION(S) FOR ANALYSIS .................................................................................................... 8

7 SAFETY AND ADVERSE EVENTS ............................................................................................................... 8

7.1 RECORDING OF ADVERSE EVENTS............................................................................................................. 10 7.2 REPORTING OF SERIOUS ADVERSE EVENTS ............................................................................................... 11

7.2.1 Study Sponsor Notification by Investigator ......................................................................................... 11 7.2.2 REC Notification by Investigator ......................................................................................................... 11

7.3 MEDICAL MONITORING ............................................................................................................................. 11

8 DATA HANDLING AND RECORD KEEPING .......................................................................................... 12

8.1 CONFIDENTIALITY ..................................................................................................................................... 12 8.2 DATA MANAGEMENT ................................................................................................................................. 12

9 STUDY AUDITING, AND INSPECTING .................................................................................................... 12

10 ETHICAL CONSIDERATIONS .................................................................................................................... 12

10.1 END OF TRIAL NOTIFICATION……………………………………………………………………………………………………….13

11 STUDY FINANCES ......................................................................................................................................... 13

1 Version 1 05/06/2013

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11.1 FUNDING SOURCE ..................................................................................................................................... 13 11.2 CONFLICT OF INTEREST ............................................................................................................................. 13 11.3 SUBJECT STIPENDS OR PAYMENTS ............................................................................................................ 13

11.4 INDEMNITY/LIABILITY AND INSURANCE……………………………………............................................................................13

12 DELEGATION OF RESPONSIBILITIES …………………………………………………………….......13

13 PUBLICATION PLAN AND ANNUAL REPORTING ............................................................................... 13

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List of Abbreviations

Abbreviation Explanation

A/E Accident and Emergency ward

AE Adverse events

CRF Case report form

DSUR Development Safety Update Reporting

EU European Union

GP General Practitioner

MgCl2 Magnesium Chloride

MHRA Medicine and Healthcare Regulatory Products

REC Research Ethics Committee

R&D Research and Development

SAE Serious Adverse Events

SSAR Suspected Serious Adverse Events

SUSARs Electronic Suspected Unexpected Serious Adverse Reaction

SPSS Statistical Product and Service Solution

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STUDY SUMMARY

Title

Does a transdermal magnesium oil spray correct a low serum

magnesium in patients with small bowel stoma

Short Title Does transdermal magnesium correct low serum magnesium

Protocol Number

Phase Not applicable

Methodology

Potential participants will have an ECG to check for cardiac

abnormality and serum magnesium analysis to confirm low magnesium

levels. Participants will then apply the 15 sprays, twice a day to their

body for 6 weeks. During this period, participants will have blood

samples taken at weeks 1, 2, 4 and 6.

Study Duration 01/06/2015 - 01/06/2016

Study Center(s) London Northwest Hospitals NHS Trust

Objectives Can magnesium oil spray correct low magnesium levels

Number of Subjects 20 patients

Inclusion Criteria

1. Patients with serum magnesium levels less than 0.66 mmol/L

2. Patients with a small bowel stoma

3. Patients aged 18 and above

4. Able to give informed consent

5. Patients would have been on the same medication (including

magnesium and vitamin D for a minimum of 4 weeks before the study

Study Product, Dose,

Route, Regimen

Product: Magnesium oil spray

Dose: 0.617mmol/spray

Route: Transdermal

Duration of

administration 10 sprays twice a day for 6 weeks (12 mmol/day)

Statistical

Methodology

The sample size was based on examining the change in magnesium

levels from baseline to 6 weeks post intervention while allowing for

10% drop out. Non-parametric statistics will be used analysis of results.

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1. INTRODUCTION

Patients with a small bowel stoma often have sodium, water and magnesium depletion. Patients

with low serum magnesium may require correction of low serum magnesium levels by either

giving magnesium tablets through the mouth (which is not well absorbed) or through a needle

passed under the skin or into a vein. Magnesium oil spray is available in many chemists. It

allows magnesium to be sprayed on the skin and absorbed through the skin with no recognized

side-effects. This trial aims to see if magnesium oil spray can be sufficient to correct a low serum

magnesium level

1.1 Rationale for current study

Watkins K and Josling PD (2010) did a pilot study on 9 patients with normal ranges of serum

magnesium levels using the magnesium oil spray. Each participant applied 20 sprays of the

magnesium oil over a 12 week period. The Hair samples of participants in this study were

analysed prior to and 12 weeks of starting the magnesium oil spray and the results showed a rise

in tissue magnesium levels. Though this was a small study, it has shown that magnesium can be

absorbed by tissues through the skin. This may be an alternative way to administer magnesium

especially as the oral preparation of magnesium is not well absorbed and giving magnesium

through a needle requires hospital admission. It would be a significant medical advance to find

an alternative way of giving magnesium to patients. Should the spray correct low magnesium

levels there is the potential to stop having a needle inserted into the skin or vein to correct low

serum magnesium levels and reduce potential complications of intravenous magnesium.

1.2 Investigational product

Magnesium oil spray (magnesium chloride).

1.3 Potential benefits

There is the potential benefit to participants and future patients with low magnesium levels to

have the chance of removing the inconvenience of regular parenteral magnesium administration

which is a burden to the patients.

1.4 Potential Risks

The study is considered to be low risk. Participants may experience tingling sensation, redness,

itching or raised bumps at body parts where spray is applied. These risks are mild, temporary and

should resolve when the participants have a shower/wash. There is no known contraindication

with other medication.

Usually a low serum magnesium level does not cause any adverse effects. Potential adverse

effects that have been recognized with severe low serum magnesium levels include: fatigue,

muscle weakness, depression, cardiac arrhythmias, ataxia, athetoid movements and convulsions.

These potential risks will be addressed by frequent monitoring of magnesium levels.

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Any health risk that arises due to the study will be treated in accordance with standard clinical

treatment protocols. Should the participants experience a skin itching, redness or rash at the site

where the magnesium spray has been applied they are advised to have a wash or shower. Should

the skin reaction occur for more than 2 days, participants are advised to call the principal

investigator (number in patient information sheet) or visit their GP.

2 STUDY OBJECTIVES

Primary objective of the study is whether magnesium oil spray can correct low magnesium

levels. Secondary objective is to identify toleration to magnesium oil spray.

3 STUDY DESIGN

Potential participants with small bowel stoma and low magnesium levels less than 0.66 mmol/L

will be identified from the out-patient gastrointestinal clinics and in-patient wards during the

screening period. The principal investigator or other members of the research team will clarify

the potential participant’s magnesium levels prior to approaching the potential participants and

then explain the study to the potential participants and provide an information sheet in the clinic.

The potential participants (patients) will have 24 hours to decide if they would enter the study.

Participants who wish to enter the study will have an ECG to check for any cardiac abnormalities

and another blood sample will be taken to verify serum magnesium levels, vitamin D,

aldosterone levels and red cell magnesium levels before being enrolled in the study. A 24 hour

urinary sample for magnesium will also be taken. They will then undergo a formal consent

process.

All participants will apply 10 sprays (6 mmol of magnesium chloride) of magnesium solution to

any of the following body parts: thighs, arms, chest, abdomen, or feet and massage it for 3

minutes. This application will be done twice a day for 6 weeks. All participants will have blood

samples taken at weeks one, three, and six along with a 24 hour urine sample at week six. The

amount of blood taken during each sample will be 2 teaspoons (10mls). Blood and urine samples

will be sent to the Northwest London Hospitals NHS Trust lab for serum and urine magnesium

analysis and to the Doctors lab for red cell magnesium analysis in line with the Human Tissue

Act 2004. Participants’ personal information will be sent with samples sent to the Northwest

London Hospitals lab while samples sent to the Doctors lab will be with a unique study identifier

assigned to each participant.

Participants will also keep records of their daily application of the magnesium oil spray in an

application diary. This diary will be submitted during each visit for blood sampling.

If serum magnesium level falls below to or below 0.3mmol/L during the study period, the

participant will be withdrawn from the trial. The participants who are withdrawn from the trial

will have their low magnesium corrected with magnesium given through the blood channel. If

more than 8 patients are withdrawn from the trial the whole trial will be abandoned.

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The data will be analysed and results will be submitted for publication in peer-reviewed journals

as well as at national or international conferences. A summary of the results will also be given to

participants should they make a request for it. It is hoped that the findings from the research will

influence the management of future patients with low serum magnesium levels due to a small

bowel stoma.

3.1 Study flow chart

Flow chart for participants with small bowel stoma (patients)

Study Period Screening Follow up after application

Week 1 Week 3 Week 6

Eligibility

check

X

Informed

consent

X

ECG X

Vitamin D

levels

X

Serum

Aldosterone

X X

Serum

magnesium

X X X X

Red cell

magnesium

X X X X

24 hour urine

sample

X X

3.2 Primary Study Endpoint(s)

Primary end point is to determine if magnesium oil spray will achieve or maintain serum levels

of magnesium above 0.66mmol.

3.3 Secondary Study Endpoint(s)

Secondary endpoint is tolerability and no side effects with the magnesium oil spray.

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4. SUBJECT SELECTION AND WITHDRAWAL

4.1 Inclusion Criteria

Patients:

Patients with small bowel stoma and serum magnesium levels less than 0.66 mmol/L.

Patients aged 18 and above.

Patients should be able to give informed consent.

Patients would have been on the same medication (including magnesium and Vitamin D)

for at least 4 weeks before the study.

Patients with normal serum albumin ranges.

4.2 Exclusion Criteria

Patients:

Pregnancy.

Serum magnesium levels less than 0.3mmol/L.

Use of magnesium containing laxatives.

Use of any non-medicinal supplements containing magnesium.

Allergy to any ingredients in the preparation or magnesium.

Oral or intravenous diuretics for 2 weeks before the trial or during the trial.

Ischaemic heart disease.

History of cardiac dysrhythmia.

Participants with extensive skin conditions such as sunburn, eczema, psoriasis.

Patients unable to give consent.

Patients with serum albumin levels below normal ranges.

4.3 Participants Recruitment and Screening

Participants with small bowel stoma and low magnesium levels will be identified and recruited

via the gastroenterology clinic and in-patient wards at the Northwest London Hospitals by the

chief investigator and other members of the research team. The participants will undergo

screening (as per study flow chart) to see if they are eligible for the study and have an ECG to

rule out any cardiac abnormality. Participants will be consented by the chief investigator,

members of the research team or members of the clinical care team who are trained in given

consent. Consent form will be attached to participants’ clinical notes and a copy will be kept in

the participants’ CRF forms (locked in a secure office).

For participants whose first language is not English and who do not understand English, the

sponsors have agreed to fund for an interpreter who would explain the study and consent in

presence of a member of the research team.

Should a participant lose capacity during the study, the participant will be withdrawn from the

study, however information generated from the study will be used in the final results.

Participants will not be recruited by publicity through posters, leaflets, adverts and websites.

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4.4 Early Withdrawal of Participants

If serum magnesium level falls below to or below 0.3mmol/L during the study period, the

participant will be withdrawn from the trial as judged by the chief investigator. Other reasons for

withdrawal include; voluntary discontinuation by the participants and if the results suggests that

8 consecutive patients have shown no improvement in their magnesium levels.

4.5 Participants follow up

It is expected that participants will be followed up for 6 weeks following administration of the

transdermal magnesium oil spray. The participants will be encouraged to fill in a monitoring

diary during the study period. This diary will be brought to the research team when they

participants attend their blood sampling follow up. The diary will be reviewed by the

investigator. At the end of the 6 weeks, diaries will be collected from participants and recorded

in a password protected computer. All diaries will be stored with the CRF forms in the chief

investigator’s office. Participants will also return all empty magnesium spray canister they have

used.

4.6 Data Collection and Follow-up for Withdrawn Participants

The Case Report Form (CRF) has to be completed up to the time of drop out. All drop outs will

continue with their standard clinical care with correction of magnesium through the vein.

Participants who are on regular oral magnesium supplements will restart their oral magnesium

supplement in addition to magnesium given through the blood channel. Replacement participants

may be included to meet the minimum data requirement.

Data on participants’ information, results of blood samples taken for serum and red cell

magnesium levels and any reaction to the magnesium oil spray will be recorded in CRF and in a

computer with a secure password. The CRFs, all patients’ information related to this research

and password protected computer will be in kept in the chief investigator’s office (a secured

room). Only the chief investigator and research personnel will have access to the CRF and

computer.

With participants who are withdrawn due to low magnesium levels despite applying the spray

will be admitted to the ward through A/E for correction of low magnesium levels. The

participant’s clinical care team will be contacted and informed of patient’s withdrawal. This is to

ensure participant’s standard of care continues.

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5. STUDY PRODUCT

5.1 Description

The product Magnesium oil spray has the product code AHLO76/2. The product is made from

natural mineral salts. It is concentrated magnesium chloride (MgCl2) brine. The magnesium oil

spray is applied transdermal.

5.2 Treatment Regimen

The participants will apply 10 sprays (6mmol of MgCl2) to the following parts of their body

(arms, chest, abdomen, thighs or thighs) and massage the area for 3minutes. This will be done

twice a day for 6 weeks. During this period participants will not be taking any non-medicinal

supplements containing magnesium.

To maintain serum magnesium levels in patients with a stoma and low serum magnesium, daily

oral dose of magnesium that is given is 12mmol (Oral magnesium is poorly absorbed).

The treatment regimen has been calculated by Eurofins as follows:

Step 1: Each spray delivers 0.14mls (15mg) of elemental magnesium.

Step 2: Molecular weight of elemental magnesium = 24.3

Step 3: 1 spray of elemental magnesium = 15mg ÷ 24.3 = 0.617mmol

Step 4: To give an equivalent of oral dose of magnesium (12mmol) = 12mmol ÷ 0.617= 19.45

sprays. This has been rounded up to 20 sprays

5.3 Preparation and Administration of Product

The MgCl2 has been prepared as a topical agent. It is administered by spray on to the skin.

5.4 Participants compliance Monitoring

The participants will be monitored for compliance by keeping an application diary. The diary

will be submitted to the research team during weekly visits for blood sampling. If there is a

persistent non-compliance from a participant, the participant will be withdrawn from the study.

5.5 Receiving, Storage, Dispensing and Return

5.5.1 Receipt of product Supplies

The product will be supplied by the sponsor to the Chief Investigator.

5.5.2 Storage

The Chief Investigator will ensure that the product is stored in a secure room and access to stored

product will be by the Chief Investigator and other members of the research team.

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5.5.3 Dispensing of Study Product

The dispensing of the product will be by the members of the research team.

6. STATISTICAL PLAN

6.1 Sample Size Determination

The sample size was based on the change in the magnesium levels from baseline to 6 weeks post

intervention. The baseline magnesium levels were expected to have a mean of 0.68 mmol/L and

an increase of 0.2mmol/L would be regarded as being clinically important. Based on the pilot

data, the standard deviation of the change in values over time is expected to be 0.3mmol/L.

Using a 5% significance level and 80% power, it is calculated that 18 patients are required for

the study. To allow for a 10% drop-out, it is proposed that 20 patients are recruited into the

study.

6.2 Statistical Methods

Data will be analysed on the SPSS version 20 software. A non-parametric statistical analysis will

be carried out.

6.3 Participants Population(s) for Analysis

The study population will be adult patients who have a small bowel stoma and a low serum

magnesium levels. We are aiming to recruit 20 participants for the study.

7. SAFETY AND ADVERSE EVENTS

Adverse Event

An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in

severity during the course of the study. Inter-current illnesses or injuries should be regarded as

adverse events. Abnormal results of diagnostic procedures are considered to be adverse events if

the abnormality:

results in study withdrawal

is associated with a serious adverse event

is associated with clinical signs or symptoms

leads to additional treatment or to further diagnostic tests

is considered by the investigator to be of clinical significance

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Serious Adverse Event

Adverse events are classified as serious or non-serious. A serious adverse event is any AE that

is:

fatal

life-threatening

requires or prolongs hospital stay

results in persistent or significant disability or incapacity

a congenital anomaly or birth defect

an important medical event

Important medical events are those that may not be immediately life threatening, but are clearly

of major clinical significance. They may jeopardize the subject, and may require intervention to

prevent one of the other serious outcomes noted above.

All adverse events that do not meet any of the criteria for serious would be regarded as non-

serious adverse events.

Pre-existing Condition

A pre-existing condition is one that is present at the start of the study. A preexisting condition

would be recorded as an adverse event if the frequency, intensity, or the character of the

condition worsens during the study period.

General Physical Examination Findings

At screening, any clinically significant abnormality should be recorded as a preexisting

condition. At the end of the study, any new clinically significant findings/abnormalities that

meet the definition of an adverse event would also be recorded and documented as an adverse

event.

Post-study Adverse Event

All unresolved adverse events would be followed by the chief and principal investigator until the

events are resolved, the subject is lost to follow-up, or the adverse event is otherwise explained.

At the last scheduled visit, the investigator would instruct each subject to report any subsequent

event(s) that the subject, or the subject’s personal physician, believes might reasonably be related

to participation in this study. The investigator would notify the study sponsor of any death or

adverse event occurring at any time after a subject has discontinued or terminated study

participation that may reasonably be related to this study.

Abnormal Laboratory Values

A clinical laboratory abnormality should be documented as an adverse event if any one of the

following conditions is met:

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The laboratory abnormality is not otherwise refuted by a repeat test to confirm the

abnormality

The abnormality suggests a disease and/or organ toxicity

The abnormality is of a degree that requires active management; e.g. change of dose,

discontinuation of the drug, more frequent follow-up assessments, further diagnostic

investigation, etc.

Hospitalization, Prolonged Hospitalization or Surgery

Any adverse event that results in hospitalization or prolonged hospitalization would be

documented and reported as a serious adverse event unless specifically instructed otherwise in

this protocol. Any condition responsible for surgery should be documented as an adverse event

if the condition meets the criteria for and adverse event.

Neither the condition, hospitalization, prolonged hospitalization, nor surgery are reported as an

adverse event in the following circumstances:

Hospitalization or prolonged hospitalization for diagnostic or elective surgical procedures

for a preexisting condition. Surgery should not be reported as an outcome of an adverse

event if the purpose of the surgery was elective or diagnostic and the outcome was

uneventful.

Hospitalization or prolonged hospitalization required to allow efficacy measurement for

the study.

Hospitalization or prolonged hospitalization for therapy of the target disease of the study,

unless it is a worsening or increase in frequency of hospital admissions as judged by the

clinical investigator.

7.1 Recording of adverse Events

At each contact with the participant, the principal investigator will seek information on adverse

events by specific questioning and, as appropriate, by examination. Information on all adverse

events will be recorded immediately in the CRF.

The clinical course of each event will be followed until resolution, stabilization, or until it has

been determined that the study treatment or participation is not the cause. Serious adverse events

that are still ongoing at the end of the study period must be followed up to determine the final

outcome. Any serious adverse event that occurs 30 days after the study period and is considered

to be possibly related to the study treatment or study participation will be recorded and reported

immediately.

Potential adverse events include:

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Symptoms of low magnesium levels: fatigue, muscle weakness, depression, cardiac

arrhythmias, ataxia, athetoid movements and convulsions that result in hospitalization of

participant.

Fall in serum magnesium levels > 0.2 mmol/L from baseline levels.

Skin rash or raised bumps due to applying magnesium spray.

Redness of skin due to applying magnesium spray.

Management of Adverse events

Participants with low magnesium levels < 0.3mmol/L or a fall > 0.2 mmol/L from baseline and

or symptoms of low magnesium will be called by a member of the research team for admission

to the ward at Northwest London Hospital and replacement of magnesium through parenteral

route.

Participants (patients and healthy participants) with skin rash for more than 2 days should stop

the spray and contact the Principal Investigator or Dr Jeremy Nightingale (Chief Investigator) via

Northwest London Hospital Switch board (24 hours)

7.2 REPORTING OF SERIOUS ADVERSE EVENTS

7.2.1 Study Sponsor Notification by Chief Investigator

A serious adverse event (SAE) will be reported to the study sponsor by telephone and email

within 24 hours of the event. A SAE form will be completed by the principal investigator and

faxed to the study sponsor within 24 hours. The research team will keep a copy of this SAE

form on file at the study site.

Within the following 48 hours, the principal investigator will provide further information on the

serious adverse event in the form of a written narrative. This should include a copy of the

completed Serious Adverse Event form, and any other diagnostic information that will assist the

understanding of the event. Significant new information on ongoing serious adverse events will

be provided promptly to the study sponsor

7.2.2 REC and R&D Notification by Chief Investigator

The REC will be notified by the chief investigator of any suspected serious adverse reaction

(SUSAR) within 7 days of the sponsors becoming aware of it. Any additional information will be

reported within 8 days of sending the first report. The R&D office will be notified within 24

hours of the SUSAR.

7.3 Medical Monitoring

The chief Investigator will oversee the safety of the study at Northwest London Hospitals NHS

Trust. This safety monitoring will include careful assessment and appropriate reporting of

adverse events as noted above, as well as the construction and implementation of a site data and

safety-monitoring plan. Medical monitoring will include a regular assessment of the number and

type of serious adverse events.

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8. DATA HANDLING AND RECORD KEEPING

8.1 Confidentiality

Data collected during this study may be used to support the development, registration and

marketing of the product. Participants’ personal information will be kept confidential according

to EU directive on data privacy concerning the processing and use of subjects’ personal data. The

Chief investigator will be the data controller.

The participants’ data will be anonymised during analysis, presentation and publication of data.

All data will be stored in a locked office and password protected computers. Only research

members will have access to the data collected from participants. Independent monitors and

auditors may be given access to participants’ personal details to verify the accuracy of the data.

8.2 Data Management

The study database will be built based on the study CRF. Data entry will be done by only

members of the research team. All data entry will occur at the study site and data will be inputted

into a secure, password protected computer.

The study will be conducted in line with the UK Data Protection Act and any other applicable

data protection legislation.

In the long term, research data will be stored for 10 years. The sponsor will arrange for the

archiving of all data collected for the study (Arrangement for achieve to be attached to protocol).

9. STUDY AUDITING AND INSPECTING

Regulatory authorities, hosting sites and REC may require inspecting and auditing the study.

The investigator will permit study-related monitoring, audits, and inspections at the study site

providing access to source data and documents.

10. ETHICAL CONSIDERATION

This study is to be conducted according to UK and international standards of Good Clinical

Practice (International Conference on Harmonization guidelines), applicable government

regulations and Institutional research policies and procedures.

This protocol and any amendments will be submitted to a Research Ethics Committee (REC) for

formal approval of the study conduct. The decision of the REC concerning the conduct of the

study will be made in writing to the investigator and a copy of this decision will be provided to

the sponsor before commencement of this study. Amendments to the study will also be

submitted to the R&D office for approval.

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10.1 End of Trial Notification

The chief investigator and or sponsor will submit an end of trial notification to the MHRA and

REC within 90 days of the end of the trial in accordance with EU directive 2001/20/EC.

For the purpose of this notification, the end of the trial will be defined as the last subject/last

visit.

11. STUDY FINANCES

11.1 Funding Source

BetterYou Ltd will be funding this study.

11.2 Conflict of Interest

The chief investigator and co-investigators have no conflict of interest with this study (patent

ownership, royalties, or financial gain greater than the minimum allowable by their institution).

11.3 Participants Stipends or Payments

The sponsor will pay travel and parking expenses incurred by the participants when attending the

study site for blood test sampling.

11.4 Indemnity/Liability and Insurance

The sponsor will adhere to the recommendations by the Association of British Pharmaceutical

Industry (ABPI) guidelines. A copy of sponsor’s indemnity/insurance will be supplied before

study initiation.

12. DELEGATION OF RESPONSIBILITIES

All trial related activities deployed to the research team members or pharmacy will be recorded

in the trial delegation log and authorized by the chief investigator.

13. PUBLICATION POLICY AND ANNUAL REPORTING

Neither the complete nor any part of the results of the study carried out under this protocol, nor

any of the information provided by the sponsor for the purposes of performing the study, will be

published or passed on to any third party without the consent of the study sponsor. Any

investigator involved with this study is obligated to provide the sponsor with complete test

results and all data derived from the study. No identifiable participant’s personal data will be

used when publishing or presenting the results.