A Randomized, Parallel-group, Evaluator-blind, No-treatment and Positive Controlled, Single-site, Proof of Concept Clinical Study to Evaluate the Cosmetic Benefit Provided by 8 Weeks of Twice-daily Topical Application of a Developmental Moisturizing Cream With Niacinamide in Healthy Subjects With Sensitive, Oily, Blemish-prone Skin
Phase: NA
Conditions: Skin Care
Sponsor: GlaxoSmithKline

Copyright:  GlaxoSmithKline.  An unpublished work subject to trade secret 
protection.  This work contains confidential and proprietary information of 
GlaxoSmithKlineand should not be copied, circulated, or distributed to persons not 
employed by GlaxoSmithKline unless specifically authorized.  Unauthorized 
disclosure of this work is expressly prohibited.
Clinical Protocol
207196
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 1 of 70

CONFIDENTIAL
SUMMARY INFORMATION
Title:
A randomised, parallel-group, evaluator-blind, no-
treatment and positive controlled, single-site, proof of 
conceptclinical study to evaluate the cosmetic benefit 
provided by 8 weeks of twice-daily topical application 
of a developmental moisturising creamwith 
niacinamide in healthy subjects withsensitive,oily, 
blemish-prone skin.
Protocol Number:
207196
Sponsor:
GlaxoSmithKline (GSK)
Rua Hungria, 1.240 -4
0andar
Jardim Europa -Sao Paulo -SP
CEP: 01455-000, Brazil
Tel: 
Product Name:
Moisturising Creamwith Niacinamide
Development Phase:
Not Applicable
Expert Advice Outside of Normal 
Working Hours:
Tel: 
Key Protocol Authors:
Clinical Research Scientist
, PhD.
GlaxoSmithKline Consumer Healthcare 
(GSKCH)
St George’s Avenue
Weybridge, Surrey, KT13 0DE
Tel: 
PRIMARY CONTACT
Clinical Study Manager:
, BSc.
GlaxoSmithKline Consumer Healthcare 
(GSKCH)
Rua Hungria, 1.240 -4
oandar
Jardim Europa -Sao Paulo -SP
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 2 of 70
PPD
PPD
PPD
PPD
PPD

CEP: 01455-000, Brazil
Tel: 
Biostatistician:
GlaxoSmithKline Consumer Healthcare 
(GSKCH)
St George’s Avenue
Weybridge, Surrey, KT13 0DE
Tel:
Other Protocol Authors:
Medically Qualified Person:
, MD, PhD.
Medical Affairs Lead:
Clinical Supplies:
, MSc.
Data Manager:
, B Pharm.
Principal Investigator:
Regina Doi, MD.
Study Site Name & Address:
Azidus Brasil -Rua General Osório, 507, 
Vila Martina, Valinhos, São Paulo, Brazil
Study Site Telephone Number:
Study Examiner(s):
Study examiners will beassigned and 
their details recorded prior to study start
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 3 of 70
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

PRINCIPAL INVESTIGATOR PROTOCOL AGREEMENT 
PAGE
1. I confirm agreement to conduct the study in compliance with the protocol and 
any amendments and according to the current International Council for 
Harmonisation (ICH) Good Clinical Practice (GCP)guidelines.
2. I acknowledge that I am responsible for overall study conduct. I agree to 
personally conduct or supervise the described study.
3. I agree to ensure that all associates, colleagues and employees assisting in the 
conduct of the study are informed about their obligations. Mechanisms are in 
place to ensure site staff receives all appropriate information throughout the 
study.
4. I agree to conduct this study in full conformance with the laws and regulations 
of the country in which the research is conducted and the Declaration of 
Helsinki.
Investigator Name:
Investigator Qualifications:
Investigator Signature:
Date of Signature/ Agreement:
DD/MMM/YYYY
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 4 of 70
PPD
PPD
PPD
PPD

TABLE OF CONTENT
SUMMARY INFORMATION...............................................2
PRINCIPAL INVESTIGATOR PROTOCOL AGREEMENT 
PAGE..............................................................................4
TABLE OF CONTENT..........................................................5
PROCESS FOR AMENDING THE PROTOCOL...............11
PROTOCOL AMENDMENT PAGE....................................12
PROTOCOL SYNOPSIS FOR STUDY 207196...................16
1. INTRODUCTION...............................................................23
2. OBJECTIVE(S) AND ENDPOINT(S)...............................24
3. STUDY PLAN.....................................................................25
3.1. Study Design.......................................................................25
3.2. Subject Restrictions...........................................................27
3.3. Type and Planned Number of Subjects............................28
3.4. Study Design and Dose Justification.................................28
4. SELECTION OF STUDY POPULATION AND 
WITHDRAWAL CRITERIA........................................31
4.1. Inclusion Criteria...............................................................31
4.2. Exclusion Criteria..............................................................32
4.3. Screening/ Baseline Failures..............................................33
4.4. Withdrawal/ Stopping Criteria.........................................34
4.5. SubjectReplacement..........................................................34
4.6. Subject and Study Completion..........................................34
5. PRODUCT INFORMATION.............................................35
5.1. Study Product.....................................................................35
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 5 of 70

5.2. Application Schedule.........................................................36
5.3. Application Modification...................................................36
5.4. Product Compliance..........................................................37
5.5. Precautions.........................................................................37
5.6. Rescue Therapy..................................................................37
5.7. Product Assignment...........................................................37
5.7.1 Randomisation....................................................................37
5.7.2 Blinding...............................................................................37
5.7.3 Code Breaks........................................................................37
5.8. Packaging and Labelling...................................................38
5.8.1. Accountability of Product.................................................38
5.8.2. Storage of Product............................................................39
6. STUDY ASSESSMENTS AND PROCEDURES..............40
6.1. Visit 1 / Day -7 to Day -5 –Screening/Washout Visit.......40
6.1.1. Informed Consent.............................................................40
6.1.2. Demographics....................................................................40
6.1.3. Medical History and Concomitant Medication...............40
6.1.4. Fitzpatrick Skin Type Assessment...................................41
6.1.5. Evaluator Assessment of Blemish Counts........................41
6.1.6 Forehead Sebumeter Measurements.................................41
6.1.7. Inclusion / Exclusion Criteria...........................................42
6.1.8. Subject Eligibility..............................................................42
6.1.9. Washout Product and Diary Dispensing..........................42
6.2. Visit 2 / Day 1 –Baseline Visit...........................................42
6.2.1. Current / Concomitant Medication..................................42
6.2.2. Diary Review (Compliance)..............................................42
6.2.3. Continued Eligibility.........................................................43
6.2.4. Evaluator Assessment of Blemish Counts........................43
6.2.5. Inclusion / Exclusion Criteria...........................................43
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 6 of 70

6.2.6. Subject Eligibility..............................................................43
6.2.7. Randomisation...................................................................43
6.2.8. Image Capture...................................................................43
6.2.9. Forehead Sebumetry Measurements................................44
6.2.10. Corneometry Measurements..........................................44
6.2.11. Sebumeter Kinetic Measurements..................................44
6.2.12. Washout Cleanser Returnand Test Product Dispensing
............................................................................................44
6.2.13. Supervised Product Application.....................................45
6.2.14. Acute Corneometer Measurements................................45
6.2.15. Adverse Events................................................................45
6.3. Visit 3 / Day 8 –1 Week of Application............................45
6.3.1. Current / Concomitant Medication..................................45
6.3.2. Diary Review (Compliance)..............................................45
6.3.3. Continued Eligibility.........................................................46
6.3.4. Evaluator Assessment of Blemish Counts........................46
6.3.5. Sebumetry Measurements................................................46
6.3.6. Corneometry Measurements............................................46
6.3.7. Sebumeter Kinetic Measurements...................................46
6.3.8. Supervised Product Application.......................................46
6.3.9. Adverse Events..................................................................46
6.4. Visit 4 / Day 29 –4 Weeks of Application.........................46
6.4.1. Current / Concomitant Medication..................................46
6.4.2. Diary Review (Compliance)..............................................46
6.4.3. Continued Eligibility.........................................................46
6.4.4. Evaluator Assessment of Blemish Counts........................47
6.4.5. Sebumetry Measurements................................................47
6.4.6. Corneometry Measurements............................................47
6.4.7. Sebumeter Kinetic Measurements...................................47
6.4.8. Supervised Product Application.......................................47
6.4.9. Adverse Events..................................................................47
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 7 of 70

6.5. Visit 5 / Day 57 –8 Weeks of Application.........................47
6.5.1. Current / Concomitant Medication..................................47
6.5.2. Diary Review (Compliance)..............................................47
6.5.3. Continued Eligibility.........................................................47
6.5.4. Evaluator Assessment of Blemish Counts........................47
6.5.5. Image Capture...................................................................47
6.5.6. Sebumetry Measurements................................................47
6.5.7. Corneometry Measurements............................................48
6.5.8. Sebumeter Kinetic Measurements...................................48
6.5.9. Test Product, Cleanser and Diary Return.......................48
6.5.10. Adverse Events................................................................48
6.5.11. Lay Person Assessment of Overall Appearance of 
Blemishes (Photographs)..................................................48
6.5.12. Discharge from Study.....................................................49
7. SAFETY ASSESSMENTS..................................................50
7.1. Definitions of an Adverse Event and Serious Adverse 
Event.................................................................................50
7.1.1. Adverse Events..................................................................50
7.1.2. Serious Adverse Events.....................................................51
7.2. Recording Adverse Events and Serious Adverse Events.52
7.3. Evaluating Adverse Events and Serious Adverse Events52
7.4. Reporting Adverse Events and Serious Adverse Events..53
7.5. Follow-up of Adverse Events and Serious Adverse Events
..........................................................................................55
7.6. Collection of Pregnancy Information................................56
7.6.1. Time Period for Collecting of Pregnancy Information...56
7.6.2. Action to be Taken if Pregnancy Occurs.........................56
8. DATA MANAGEMENT....................................................57
8.1. Source Documents/ Data....................................................57
8.2. Electronic Case Report Form............................................57
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 8 of 70

8.3. Data Handling....................................................................58
8.3.1. Data Queries......................................................................58
9. STATISTICAL CONSIDERATIONS AND DATA 
ANALYSES....................................................................59
9.1 Sample Size Determination.................................................59
9.2. General Considerations.....................................................59
9.2.1. Definition of Analysis Populations...................................59
9.2.2. Exclusion of Data from Analysis......................................60
9.2.3. Criteria for Evaluation.....................................................60
9.2.4. Handling of Dropouts and Missing Data.........................60
9.3. Statistical Methods and Analytical Plan...........................60
9.3.1. Demographic and Baseline Characteristics.....................60
9.3.2. Primary Analysis(es).........................................................60
9.3.3. Secondary Analysis(es).....................................................61
9.3.4. Safety Analysis(es).............................................................61
10. STUDY GOVERNANCE CONSIDERATIONS.............63
10.1. Posting of Information on Publicly Available Clinical 
Trials Registers................................................................63
10.2. Regulatory and Ethical Considerations, Including the 
Informed Consent............................................................63
10.3. Quality Control (Study Monitoring)...............................63
10.4. Quality Assurance............................................................64
10.5. Conditions for Terminating the Study............................64
10.6. Records Retention............................................................65
10.7. Provision of Study Results to Investigators, posting of 
Information on Publicly Available Clinical Trials 
Registers and Publication................................................66
11. REFERENCES..................................................................67
12. APPENDICES...................................................................68
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 9 of 70

Appendix 1 -Abbreviations and Trademarks.........................68
Appendix 2 –Inclusion / Exclusion Criteria for Review at Visit 
2........................................................................................69
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 10 of 70

PROCESS FOR AMENDING THE PROTOCOL
Protocol modifications to ongoing studies which could potentially adversely affect the 
safety of subjects or which alter the scope of the investigation, the scientific quality of 
the study, the experimental design, dosages, duration of therapy, assessment 
variables, the number of subjects treated, or subject selection criteria are considered 
major/substantial amendments and must be made only after appropriate consultation 
between an appropriate representative ofGlaxoSmithKline Consumer Healthcare 
(GSKCH)and the investigator.
Details of amendments to the protocols should be recorded on the following page. 
Protocol modifications must be prepared by a representative of GSKCH.  All changes 
must be justified in the Reason for Amendment section of the following Protocol 
Amendment Page. Approval of amendments will be made by the original protocol 
signatories or their appropriate designees.
All major/substantial protocol modifications must be reviewed and approved by the
appropriate Independent Ethics Committee (IEC)in accordance with local 
requirements, before the revised edition can be implemented. 
All non-substantial/ minor/ administrative amendments should be submitted to the 
IECas per country specific requirements. In some countries pre-approval of a minor 
amendment is not required and will just be held on file by the sponsor and 
investigator.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 11 of 70

PROTOCOL AMENDMENT PAGE
Details of all amendments should be recorded in the table below. Affected sections should be listed in the table; the actual 
amendment/ change should be made in the relevant section of the main protocol. 
To highlight the change, the following features will be used: 
To addtext: Use of CAPITAL LETTERS, BOLD AND UNDERLINE
To delete text: Use of Strikethrough e.g. strikethrough
Amendment 
No. & New 
Protocol 
Version No.
Type of Amendment
Reason for Amendment
Other 
Documents 
Requiring 
Amendment
Section(s) Amended 
PI Amendment 
Agreement
Signature & 
Date
Amendment 
No.:1
Non-Substantial/Minor    To correct an error pertaining 
to the location of the 
Fitzpatrick assessment scale.
Informed 
Consent   
Yes No
Safety 
Statement     
Yes No
CRF                       
Yes No
4.1 Inclusion 
Criteria (page 30)
Signature:
Protocol 
Version 
No.:2
Substantial/ Major           
Date:
Amendment 
No.:2
Non-Substantial/Minor    To remove the sub-totals for 
the blemish counts, which 
will no longer be collected on 
the CRF. To add text 
clarifying that a grand total of 
blemish counts will be 
automatically calculated on 
the CRF at Visits 1 and 2.
Informed 
Consent   
Yes No
Safety
Statement     
Yes No
CRF                       
Yes No
6.1.5. Evaluator 
Assessment of 
Blemish Counts 
(page 40)
Signature:
Protocol 
Version 
No.:2
Substantial/ Major           
Date:
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
PPD
PPD
PPD
PPD

Amendment 
No. & New 
Protocol 
Version No.
Type of Amendment
Reason for Amendment
Other Documents 
Requiring 
Amendment
Section(s)
Amended 
PI Amendment 
Agreement
Signature & 
Date
Amendment 
No.: 3
Non-Substantial/Minor    
To clarify that Corneometer 
measurements will only be 
taken in triplicate at the left 
cheek and not both the right and 
left cheeks.
Informed Consent   
Yes 
No
Safety Statement     
Yes 
No
CRF                       
Yes 
No
6.2.10. 
Corneometry 
Measurements
(Page 43)
Signature:
Protocol 
Version 
No.:2
Substantial/ Major           
Date:
Amendment 
No.:4
Non-Substantial/Minor    
To add time windows for the 
Corneometer and Sebumeter
Kineticmeasurements
Informed Consent   
Yes 
No
Safety Statement     
Yes 
No
CRF                       
Yes 
No
Schedule of 
Events (Page 14); 
Study Design 
(Page 17-19); 3.2 
Study Design 
(Page 25-26); 
6.2.11 (Page 43); 
6.2.14 (Page 44)
Signature:
Protocol 
Version 
No.:3
Substantial/ Major           
Date:
Amendment 
No.: 5
Non-Substantial/Minor    
To reduce the minimum number 
of blemishes at screening from 
10 to 8 and to permit 
rescreening of screen-failed 
subjects due to this inclusion 
criterion in order to address 
recruitment challenges. 
Contact information for GSK 
Statistician and Clinical Study
Manager have also been 
Informed Consent   
Yes 
No
Safety Statement     
Yes 
No
CRF                       
Yes 
No
Screening (Page 
32); Study Design 
and dose 
justification (Page 
27);Inclusion 
criteria (Page 30, 
Page 68)
Signature:
Protocol 
Version 
No.: 4
Substantial/ Major           
Date:
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
PPD
PPD
PPD
PPD
PPD
PPD

updated.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0

SCHEDULE OF EVENTS
Procedure/Assessment
Visit 1
Day -5 to -
7
Visit 2
Day 1
Visit 3
Day 8
+/-1 Day
Visit 4
Day 29 
+/-2 Days
Visit 5
Day 57
+/-2 Days
Screening 
/ Washout Baseline
1 Week of 
Application
4 Weeks of 
Application
8 Weeks of 
Application
Informed Consent
X
Demographics
X
Medical History
X
Current / Concomitant Medication
X
X
X
X
X
Adverse Events
X
X
X
X
Diary Review (Compliance)1
X
X
X
X
Continued Eligibility
X
X
X
X
Fitzpatrick Skin Type Assessment
X
Evaluator Assessment ofBlemishCounts2
X
X4
X
X
X
Forehead Sebumeter Measurement3
X
X4
X
X
X
Inclusion / Exclusion Criteria
X
X5
Subject Eligibility
X
X
Washout Cleanser and Diary Dispensing
X
Randomisation
X
Corneometer Measurements3
X4
X
X
X
Image Capture
X4
X
Washout Cleanser Return and Products
Dispensing
X
Sebumeter Kinetic Measurements3,9
X
X
X
X
Supervised Product Application6
X
X
X
Acute Corneometer Measurements
X7
Productsand Diary Return
X
Subject Discharge from Study
X
Lay Person Assessment of Overall Appearance 
of Blemishes (Photographs)
8
X
1. Evaluators must be blinded to diary review. 
2. Blind evaluator assessment of papules and pustules, to be counted separately for the face, chin and cheeks.
3. Subjects must also acclimatize for a minimum of 30 minutes in a temperature (20±1degrees Celsius (ºC)) and humidity(50±10%Relative 
Humidity (RH)) controlled room prior to any instrumental measurement being taken.
4. Baseline measurements (prior to any product application).
5. Only theinclusion and exclusion criteria in Appendix 2 will be reviewed at this visit.
6. Subjects randomised to positive control regimen will apply the positive control cleanser and positive control cream. Subjects randomised to thetest 
product regimen will applythe standard cleanser and test product.Subjects randomised to the no treatment regimen will apply the standard cleanser, 
only.Test product application will be overseen by a member of the study team who must not be involved in any clinical or instrumental assessment 
which could influence the study outcome. 
7. Acute Corneometer assessments will be taken 1hour± 15 MINUTES, 3 hours± 15 MINUTESand 8 hours ± 15 MINUTESafter applicationof the 
cream for subjects randomised to thetest product and positive controlregimens and after cleansing for subjects randomised to the untreated regimen.
8. Lay person assessment of overall appearance of blemishes (Photographs) will take place after the completion of the clinical study. 
9. SEBUMETERKINETICMEASURMENTS WILL BE TAKEN 5 ± 1 MINUTE AND 90 ± 5 MINUTES AFTER FOREHEAD CLEANSING.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 15 of 70

PROTOCOL SYNOPSIS FOR STUDY 207196
Brief Summary
A randomised, parallel-group, evaluator-blind, no-treatment and positive controlled, 
single-site, proof of conceptclinical study to evaluate the cosmetic benefit provided 
by 8 weeks of twice-daily topical application of a developmental moisturising cream
with niacinamide in healthy subjects withsensitive,oily, blemish-prone skin.  
Cosmetic creams containing niacinamide have been shown to help improve the 
moisturisation of the stratum corneum, improve the rate of desquamation, normalize 
sebum levels and reduce the appearance of blemishes.
It is therefore hypothesized that the test product, which is also formulated as a 
cosmetic cream containing niacinamide, will help moisturise the skin, support 
efficientdesquamation of the stratum corneum and prevent excessive aggregation of 
corneocytes in the follicles, a known trigger implicated in the development of 
blemishes. These cosmetic benefits should translate to an overall improvement in the 
appearance of the complexion of people with blemish-prone skin.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 16 of 70

Objective(s) and Endpoint(s)
Objective(s)
Endpoint(s)
Primary
Evaluation of skin moisturisation
(change from baseline) compared to no 
treatment
Corneometer values at 8 hourson Day 1
Secondary
Evaluation of skin moisturisation
(change from baseline) compared to no 
treatment
Corneometer values at 1 houron Day 1, 3 
hourson Day1, 1 week, 4 weeks and 8 
weeks
Evaluation of the overall appearance of 
blemishes (change from baseline) 
compared to no treatment
Lay person assessment of the appearance 
of blemishes by photographic assessment 
at 8 weeks
Evaluator assessment blemish count(sum 
of papulesandpustules atforehead, chin 
and cheeks) at 1, 4 and 8 weeks
Evaluator assessment of individual blemish 
count(individual count of papulesand
pustules at the forehead, chin and cheeks)
at 1, 4 and 8 weeks
Evaluation of skin oiliness 
improvement (change from baseline) 
compared to no treatment
Sebumeter values at 1, 4 and 8 weeks
Sebum excretion rate at 1, 4 and 8 weeks
To evaluate the safetyof the test 
product
Frequency and severity of adverse events
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 17 of 70

Study Design
Overall Design
Arandomised, parallel-group, evaluator-blind, no-treatment and positive controlled, 
single-site, proof of conceptclinical studyto evaluate the cosmetic benefit provided 
by 8 weeks of twice-daily topical application of a developmental moisturising cream
with niacinamide in healthy subjects withsensitive,oily, blemish-prone skin.
Visit 1(Day -5 to -7)–Screening / Washout Visit
The following assessments will be conducted:
1. Informed Consent
2. Demographics
3. Medical History
4. Current / Concomitant Medication
5. Fitzpatrick Skin Type Assessment
6. Evaluator Assessment of Blemish Counts
7. Forehead Sebumeter Measurements
8. Inclusion / Exclusion Criteria
9. Subject Eligibility
10.Washout Cleanserand Diary Dispensing
Visit 2 / Day 1 –Baseline Visit 
The following assessments will be conducted:
1. Current / Concomitant Medication
2. Diary Review (Compliance) 
3. Continued Eligibility
4. Evaluator Assessment of Blemish Counts
5. Inclusion / Exclusion Criteria*
6. Subject Eligibility
7. Randomisation
8. Image Capture
9. Forehead Sebumeter Measurements
10.Corneometer Measurements
11.Sebumeter Kinetic Measurements**
12.Washout Cleanser Return and Test Product Dispensing
13.Supervised Test Product Application
14.Acute Corneometer Measurements***
15.Adverse Events
*To include a review of the inclusion and exclusion criteria specified in Appendix 2
**SEBUMETER MEASURMENTS WILL BE TAKEN 5 ± 1 MINUTE AND 90 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 18 of 70

± 5 MINUTES AFTER FOREHEAD CLEANSING.
***Acute Corneometer measurements to be taken 1HOUR ± 15 MINUTES, 3
HOURS ± 15 MINUTESand 8 hours±15 MINUTESafter test product or positive 
control application for subjects randomised to the test product and positive control
regimensand after cleansingfor subjects randomised to the untreated regimen.
Visit 3/ Day 8±1 Day –1 Weekof Application
The following assessments will be conducted:
1. Current / Concomitant Medication
2. Diary Review (Compliance)
3. Continued Eligibility
4. Evaluator Assessment of Blemish Counts
5. Forehead Sebumeter Measurements
6. Corneometer Measurements
7. Sebumeter Kinetic Measurements*
8. Supervised Test Product Application
9. Adverse Events
*SEBUMETER KINETIC MEASURMENTS WILL BE TAKEN 5 ± 1 
MINUTE AND 90 ± 5 MINUTES AFTER FOREHEAD CLEANSING.
Visit 4 / Day 29±2Days–4Weeks of Application
The following assessments will be conducted:
1. Current / Concomitant Medication
2. Diary Review (Compliance)
3. Continued Eligibility 
4. Evaluator Assessment of Blemish Counts
5. Forehead Sebumeter Measurements
6. Corneometer Measurements
7. Sebumeter Kinetic Measurements*
8. Supervised Test Product Application
9. Adverse Events
**SEBUMETER KINETIC MEASURMENTS WILL BE TAKEN 5 ± 1 
MINUTE AND 90 ± 5 MINUTES AFTER FOREHEAD CLEANSING.
Visit 5/ Day 57±2Days–8 Weeks of Application 
The following assessments will be conducted in the order written:
1. Current / Concomitant Medication
2. Diary Review (Compliance)
3. Continued Eligibility
4. Evaluator Assessment of Blemish Counts
5. Image Capture
6. Forehead Sebumeter Measurements
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 19 of 70

7. Corneometer Measurements
8. Sebumeter Kinetic Measurements*
9. Test Product, Cleanser and Diary Return
10.Adverse Events
11.Subject Discharge from Study
12.Lay Person Assessment of Overall Appearance of Blemishes (Photographs)**
*SEBUMETER KINETIC MEASURMENTS WILL BE TAKEN 5 ± 1 
MINUTE AND 90 ± 5 MINUTES AFTER FOREHEAD CLEANSING.
**This procedure will take place after all the subjects have been discharged from the 
study.
Type and Planned Number of Subjects
Approximately 200female subjects aged 18-45 with self-assessed sensitive skin and a 
minimum of 108and a maximum of 25 facialblemishes (papules and pustules, 
excluding the nose)will be screened to randomise 132 healthy subjects, to ensure 
approximately 40 subjects in the test productregimen,40 subjects in the no treatment 
regimen and 40 subjects in the positive control regimencomplete the study (assuming 
a 10% dropout rate). Randomisationwill be stratified by age (<21 years old, >21 
years of age).  
The sample size was based on clinical considerations. In a previous study of a 
cosmetic product, counts of papules and pustules decreased from a baseline mean of 
27.6 to a mean of 13.5 at Week 8 (ref. Shalita 1995 IJD). With 40 subjects in both the 
test product and no-treatment regimens, a difference between groups at least 60% the 
magnitude of the standard deviation (assumed equal for both groups) would be 
detectable at two-sided alpha=0.05 with approximately 80% power.
Main Criteria for Inclusion
Healthy female subjectsaged 18-45 with oily, self-assessed sensitive skin and a 
minimum of 108blemishes (papules and pustules) and a maximum of 25 blemishes 
on the facewill be recruited for this study. Subjects must not currently have acne 
conglobate, fulminans, secondary acne (drug induced acne) nodular lesions or any 
acne requiring systemic or topical treatment. Subjects must not have a history of 
usinga medicated acne treatment within thelast 12months.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 20 of 70

Product Information
Washout / 
Standard 
Cleanser
Test Product
Positive 
Control 
Cleanser
Positive 
Control 
Moisturiser
Product Name 
Simple Kind 
to Skin 
Moisturising 
Facial Wash
Moisturising 
Cream with 
Niacinamide
Neutrogena 
Visibly Clear 
Spot Clearing 
Facial Wash
Vivatinell 
Acnecinamide 
Gel Cream
Product 
Formulation 
Code (MFC)
Commercially 
Available 
(UK)
Commercially 
Available 
(UK)
Commercially 
Available 
(Turkey)
Application 
Quantity
Approx. 0.6 g
Approx. 0.6 g Approx. 0.6 g Approx. 0.6 g
Application 
Instructions
Use twice daily 
(morning and 
night)with at 
least 8 hours 
between 
product 
applications.
Wet your face 
and hands with 
water. Dispense 
the product into 
your hands and 
apply to the
face. Massage 
gently. Rinse 
with water and 
pat dry.
Avoid contact 
with eyes. If 
contact occurs, 
rinse thoroughly 
with water.
Use twice daily 
(morning and 
night)with at 
least 8 hours 
between product 
applications.
Dispense two 
pumps of 
product onto 
your fingertips 
and apply to 
your whole 
face, covering 
all blemishes.
Avoid contact 
with eyes. If 
contact occurs, 
rinse thoroughly 
with water.
Use twice daily 
(morning and 
night)with at 
least 8 hours 
between product 
applications.
Wet your face 
and hands with
water. Dispense 
the product into 
your hands and 
apply to the 
face. Massage 
gently. Rinse 
with water and 
pat dry.
Avoid contact 
with eyes. If 
contact occurs, 
rinse thoroughly 
with water.
Use twice daily 
(morning and 
night)with at 
least 8 hours 
between product 
applications.
Apply a pea-
sized quantity to 
your whole 
face, covering 
all blemishes.
Avoid contact 
with eyes. If 
contact occurs, 
rinse thoroughly 
with water.
Statistical Methods
A formal statistical analysis plan will be prepared prior todatabase finalization.
All efficacy analyses will be performed on the ITT population defined as all subjects 
randomized with at least one post-baseline study assessment. Safety analyses will be 
based on the safety population defined as all treated subjects.For the no treatment 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 21 of 70
CCI

regimen, treatment is defined as at least one use of the washout cleanser post-
randomisation. No statistical comparison between the positive control regimen and 
the test product regimen is planned.
The change from baseline in Corneometermeasurementat 8 hours post-treatment on 
Day 1(primary endpoint) will be summarized by age stratum, treatment regimen and 
study visit using means and 95% confidence intervals and compared between 
treatment regimenusing analysis of covariance (ANCOVA) with treatment main 
effect, age stratum (<21, >21 years of age)and baseline measurement as covariate or 
Wilcoxon rank sum test, depending on the data distribution. Differences between 
least squares means for the test product and no treatment regimen will be presented, 
together with 95% confidence intervals. While for this proof of conceptstudy 
statistical significance (p<0.05) may not be achieved, these results will drive sample 
size projections for future studies.
The secondary Corneometer and Sebumeter changes from baseline will be 
summarized by age stratum, treatment regimenand study visit and analysed using the 
ANCOVAmodel described above.
Clinical assessment of blemish counts (papules and pustules) will be summarized by 
age group stratum (<21, >21 years of age), treatment regimen and study visit and 
compared between treatmentregimens usingmeans and 95% confidence intervals and 
compared between treatment regimenusing analysis of covariance (ANCOVA) with 
treatment main effect, age stratum (<21, ≥21 years of age)and baseline countas 
covariate or Wilcoxon rank sum test, depending on the data distribution. Differences 
between least squares means for the test product and no treatment regimen will be 
presented, together with 95% confidence intervals.  
The lay person assessment resulting from the ranking of images will inherently be an 
assessment of change from baseline. As such, the data resulting from these rankings 
will be tabulated by treatment regimen as proportions with baseline image better and 
Day 57 image better and analysed using a logistic regression.
Adverse events will be tabulated by age stratum and treatment regimenand displayed.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 22 of 70

1. INTRODUCTION
Thisrandomised, parallel-group, evaluator-blind, no-treatment and positive 
controlled, single-site, proof of conceptclinical studyis designedto evaluate the 
cosmetic benefit provided by 8 weeks of twice-daily topical application of a 
developmental moisturising creamwith niacinamide in healthy subjects with
sensitive,oily, blemish-prone skin.  
The process by which facial blemishes appear usually begins with blocked follicles, 
which can be caused by inefficient desquamation of dead skin cells in the stratum 
corneum.  Once blocked, sebum and additional dead skin cells can build up behind 
the blockage to create a comedone, commonly referred to as a blackhead or 
whitehead. Inaddition, the environment inside the blocked follicle is anaerobic, 
which promotes the propagation of bacteria that can trigger the redness associated 
with the appearance of blemishes, commonly referred to as papules and pustules.
It is well established that regular use of cosmetic creams containing niacinamide can 
help moisturise the skin, ensure efficient desquamation of the stratum corneum and 
normalize sebum levels. It is therefore expected that the test product will help 
promote efficient desquamation and prevent follicles from becoming blocked, thereby 
preventing the formation of new blemishes. Thesecosmetic benefits shouldtranslate 
to an overall improvement in the appearance of the complexion of people with 
blemish-prone skin.
The inclusion of a positive control regimen (Neutrogena Visibly Clear Spot Clearing 
Facial Wash and Vivatinell Acnecinamide Gel Cream) will help to validate the design 
of the trial by confirming the detectable cosmetic benefits of moisturisation and 
overall appearance of blemishes. 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 23 of 70

2. OBJECTIVE(S) AND ENDPOINT(S)
Objective(s)
Endpoint(s)
Primary
Evaluation of skin moisturisation
(change from baseline) compared to no 
treatment
Corneometer values at 8 hourson Day 1
Secondary
Evaluation of skin moisturisation
(change from baseline) compared to no 
treatment
Corneometer values at 1 hour on Day 1, 3 
hours on Day 1, 1 week, 4 weeks and 8
weeks
Evaluation of the overall appearance of 
blemishes (change from baseline) 
compared to no treatment
Lay person assessment of the appearance 
of blemishes by photographic assessment 
at 8 weeks
Evaluator assessment blemish count(sum 
of papulesandpustules atforehead, chin 
and cheeks) at 1, 4 and 8 weeks
Evaluator assessment of individual blemish 
count(individual count of papulesand
pustules at the forehead, chin and cheeks)
at 1, 4 and 8 weeks
Evaluation of skin oiliness 
improvement (change from baseline) 
compared to no treatment
Sebumeter values at 1, 4 and 8 weeks
Sebum excretion rate at 1, 4 and 8 weeks
To evaluate the safetyof the test 
product
Frequency and severity of adverse events
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 24 of 70

3. STUDY PLAN
3.1. Study Design
Overall Design
Arandomised, parallel-group, evaluator-blind, no-treatment and positive controlled, 
single-site, proof of conceptclinical studyto evaluate the cosmetic benefit provided 
by 8 weeks of twice-daily topical application of a developmental moisturising cream
with niacinamide in healthy subjects withsensitive,oily, blemish-prone skin.
Visit 1(Day -5 to -7)–Screening / Washout Visit
The following assessments will be conducted:
11.Informed Consent
12.Demographics
13.Medical History
14.Current / Concomitant Medication
15.Fitzpatrick Skin Type Assessment
16.Evaluator Assessment of Blemish Counts
17.Forehead Sebumeter Measurements
18.Inclusion / Exclusion Criteria
19.Subject Eligibility
20.Washout Cleanserand Diary Dispensing
Visit 2 / Day 1 –Baseline Visit 
The following assessments will be conducted:
16.Current / Concomitant Medication
17.Diary Review (Compliance) 
18.Continued Eligibility
19.Evaluator Assessment of Blemish Counts
20.Inclusion / Exclusion Criteria*
21.Subject Eligibility
22.Randomisation
23.Image Capture
24.Forehead Sebumeter Measurements
25.Corneometer Measurements
26.Sebumeter Kinetic Measurements**
27.Washout Cleanser Return and Test Product Dispensing
28.Supervised Test Product Application
29.Acute Corneometer Measurements***
30.Adverse Events
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 25 of 70

*To include a review of the inclusion and exclusion criteria specified in Appendix 2
**SEBUMETER MEASURMENTS WILL BE TAKEN 5 ± 1 MINUTE AND 90 
± 5 MINUTES AFTER FOREHEAD CLEANSING.
***Acute Corneometer measurements to be taken 1HOUR ± 15 MINUTES, 3
HOURS ± 15 MINUTESand 8 hours±15 MINUTESafter test product or positive 
control application for subjects randomised to the test product and positive control
regimensand after cleansing for subjects randomised to the untreated regimen.
Visit 3/ Day 8±1 Day –1 Weekof Application
The following assessments will be conducted:
10.Current / Concomitant Medication
11.Diary Review (Compliance)
12.Continued Eligibility
13.Evaluator Assessment of Blemish Counts
14.Forehead Sebumeter Measurements
15.Corneometer Measurements
16.Sebumeter Kinetic Measurements*
17.Supervised Test Product Application
18.Adverse Events
*SEBUMETER KINETIC MEASURMENTS WILL BE TAKEN 5 ± 1 
MINUTE AND 90 ± 5 MINUTES AFTER FOREHEAD CLEANSING.
Visit 4 / Day 29±2Days–4 Weeks of Application
The following assessments will be conducted:
10.Current / Concomitant Medication
11.Diary Review (Compliance)
12.Continued Eligibility 
13.Evaluator Assessment of Blemish Counts
14.Forehead Sebumeter Measurements
15.Corneometer Measurements
16.Sebumeter Kinetic Measurements*
17.Supervised Test Product Application
18.Adverse Events
**SEBUMETER KINETIC MEASURMENTS WILL BE TAKEN 5 ± 1 
MINUTE AND 90 ± 5 MINUTES AFTER FOREHEAD CLEANSING.
Visit 5/ Day 57±2Days–8 Weeks of Application 
The following assessments will be conducted in the order written:
13.Current / Concomitant Medication
14.Diary Review (Compliance)
15.Continued Eligibility
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 26 of 70

16.Evaluator Assessment of Blemish Counts
17.Image Capture
18.Forehead Sebumeter Measurements
19.Corneometer Measurements
20.Sebumeter Kinetic Measurements*
21.Test Product, Cleanser and Diary Return
22.Adverse Events
23.Subject Discharge from Study
24.Lay Person Assessment of Overall Appearance of Blemishes (Photographs)**
*SEBUMETER KINETIC MEASURMENTS WILL BE TAKEN 5 ± 1 
MINUTE AND 90 ± 5 MINUTES AFTER FOREHEAD CLEANSING.
**This procedure will take place after all the subjects have been discharged from the 
study.
3.2. Subject Restrictions
Lifestyle/ Dietary
During the entire study (screening –Last Subject Last Visit (LSLV));
1. Subjects must not takeholiday outside of their home country.
2. Subjects must avoid water sports including sailing, diving, swimming and 
winter sports including skiing and snowboarding. 
Medications and Treatments
On the day of site visit;
1. Subjects must cleanse their face with water (only). 
2. Subjects must not apply any other cosmetic or medicated treatment on the 
face, including the test products provided.
During the entire study (screening –LSLV);
1. Subjects must not apply any other cosmetic or medicated treatment on the 
face, other than the test products provided.
2. Subjects may continue to wear their current brand of mascara and lipstick but 
must not use any facial cosmetics (e.g. blusher, foundation, tinted moisturiser, 
eyeshadow).
3. Subjects must not change their brand or usage of shampoo, shower gel, hand 
soap and other cosmetic products otherwise used on the body.
4. Female subjects of child-bearing potential must use effective contraception.
5. Subjects must not changeany hormonal treatment or contraception that they 
may be receiving and must have used the same contraception for 3 months 
prior to screening.
6. Subjects must not undergo any aesthetic,cosmetic or dermatological 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 27 of 70

treatment in the treatment area (face or eyes)
7. Subjects must not use any study prohibited medication as specified in the 
exclusion criteria.
8. Subjects must avoid photodynamic therapy, laser therapy, microdermabrasion 
for acne.
9. Subject must avoidsunbathing, ultraviolet (UV) treatments and tanning 
salons.
10.The use of sunscreen on the face is not permitted.
3.3. Type and Planned Number of Subjects
Approximately 200 female subjects aged 18-45 with self-assessed sensitive skin and a 
minimum of 108and a maximum of 25 facialblemishes (papules and pustules, 
excluding the nose)will be screened to randomise 132 healthy subjects, to ensure 
approximately 40 subjects in the test productregimen,40 subjects in the no treatment 
regimen and 40 subjects in the positive control regimencomplete the study 
(Assuming a 10% dropout rate). Randomisationwillbe stratified by age (<21 years 
old, >21 years of age).  
The sample size was based on clinical considerations. In a previous study of a 
cosmetic product, counts of papules and pustules decreased from a baseline mean of 
27.6 to a mean of 13.5 at Week 8 (ref. Shalita 1995 IJD). With 40 subjects in both the 
test product and no-treatment regimens, a difference between groups at least 60% the 
magnitude of the standard deviation (assumed equal for both groups) would be 
detectable at two-sided alpha=0.05 with approximately 80% power.
3.4. Study Design and Dose Justification
This proof of concept study is part of a broader development program to bring to 
market a range of cosmetic products targeted at female adults with sensitive, blemish-
prone skin.  The study is designed as a randomised, parallel-group, evaluator-blind, 
positive and no-treatment controlled, single-site, clinical study to evaluate the 
cosmetic benefitsprovided by 8 weeks of twice-daily topical application of a 
developmental moisturising cream with niacinamide in healthy subjects with 
sensitive, oily, blemish-prone skin.
For the purpose of this clinical study a steady state approximation is assumed, i.e. that 
the rate at which new blemishes appear is equal to the rate at which blemishes 
disappear. As this product is designed to prevent new blemishes from forming by 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 28 of 70

ensuring the skin is well moisturised to facilitate efficient desquamation, it is 
expected that there will be a preventative effect on the rate at which new blemishes 
appear. To account for natural fluctuations in blemish counts, subjects will only be 
enrolled into the washout phase if they have a minimum of 108and a maximum of 
25 facial blemishes (papules and pustules), excluding the nose.
NOTE: ON 9 MAY 2017 THE SPONSOR AGREED TO RELAX THE 
SCREENING CRITERIA TO ENABLE INCLUSION OF SUBJECTS WITH A 
MINIMUM OF 8 FACIAL BLEMISHES IN ORDER TO FACILITATE 
RECRUITMENT.THIS AMENDMENT HAS NO IMPACT ON THE 
STATISTICAL POWER OF THE STUDY AS THE INCLUSION/EXCLUSION 
CRITERIA FOR RANDOMISATION ARE UNCHANGED.
Male subjects are excluded from this study to avoid the confounding impact of facial 
shaving on clinical assessments. Adolescent subjects and subjects older than 45 years 
are excluded as they do not represent the target population for the product.
Subjects with ahistory of using a medicated acne treatment within the last 24 months 
and subjects who, in the opinion of the investigator, require medicated acne treatment 
willnot be enrolled in the study as they do not represent the target population for the 
cosmetic products.
Therefore, approximately 200 female subjects aged 18-45 with self-assessed sensitive 
skin and a minimum of 108and a maximum of 25 facialblemishes (papules and 
pustules, excluding the nose)will be screened to randomise 132 healthy subjects, to 
ensureapproximately 40 subjects in the test product regimen, 40 subjects in the no 
treatment regimenand 40 subjects in the positive control regimencomplete the study 
(assuming a 10% dropout rate). Randomisation will be stratified by age (<21 years 
old, >21 years of age).
A 5-7 day washout period is included to standardize subjects’ cleansing and skin care 
regimens prior to entering the test phase. Subjects will be instructed not to use any 
skin care or cosmetic product during the washout phase and to cleanse twice a day 
(morning and night) with the washout facial cleanser provided(Simple Kind to Skin 
Moisturising Facial Wash; Commercially Available (UK)).To remain eligible for this 
study, subjects must complete the washout period (assessed at Visit 2) with at least 8 
blemishes (papules and pustules, excluding the nose).
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 29 of 70

Following the washout period, subjects who continue to be eligible for the study will
be randomised to one of three treatment regimens (no treatment + standard cleanser,
test product+ standard cleanser,or positive controlcream + positive control 
cleanser). Due to the natural fluctuations of facial blemishes, the negative control, no-
treatment regimen, is included to provide an anchor for efficacy assessments. All 
efficacy comparisons of thetest product will be to the no-treatment regimen.
A cosmetic moisturising cream with niacinamide reported efficacious in subjects with 
blemish-prone skin (Vivatinell Acnecinamide Gel Cream) and a cosmetic cleanser 
containing 2% Salicylic Acid for exfoliation (Neutrogena Visibly Clear Spot Clearing 
Facial Wash)comprise a positive control regimen to support validation of the clinical 
study. No statistical comparison between the positive control regimen and the test 
product is planned.
The test product and no treatment regimens include a standard cleanser (Simple Kind 
to Skin Moisturising Facial Wash) that has not been designed to deliver 
improvements in the appearance of blemishes to enable the efficacy of the test 
product to be accurately evaluated. 
During the test phase, subjects randomised to test product or positive control regimen 
will be instructed to use the cleanser and test/control products twice a day (morning 
and night). Subjects randomised to the no treatment regimen will use the standard 
cleanser (only) twice a day. The first application of the standard cleanser or positive 
control cleanser will be at the site, under supervision of the Investigator or designee 
who will provide instruction on how to correctly apply the product. The first 
application of test product or positive control will be conducted by the subject at the 
site, after cleansing, under the supervision of the Investigator or designee who will 
provide instruction on how to correctly apply the product. 
Blinded evaluatorand instrumental assessments will be taken after the washout 
period(baseline) andafter 7, 28 and 56 days of twice-daily product use. All 
reasonable efforts will be made to ensure the same Evaluator assesses the same 
subject at each visit. 
The Investigator or designee will dispense adiary to all subjectsto monitor and 
encourage compliance. This diary will be reviewed at each site visit by the 
Investigator or designeeand missed/extra applications recorded as deviations.The
Investigator or designee will observe the subject applying the products and, if needed, 
will instruct the subject how to correctly apply them.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 30 of 70

4. SELECTION OF STUDY POPULATION AND 
WITHDRAWAL CRITERIA
Specific information regarding warnings, precautions, contraindications, adverse 
events, and other pertinent information on the GSK investigational product or other 
study treatment that may impact subject eligibility is provided in the safety statement.
Deviations from inclusion and exclusion criteria are not allowed because they can 
potentiallyjeopardize the scientific integrity of the study, regulatory acceptability or 
subject safety. Therefore, adherence to the criteria as specified in the protocol is 
essential.
4.1. Inclusion Criteria
A subject will be eligible for inclusion in this study only if all of the following criteria 
apply:
1. CONSENT
Demonstrates understanding of the study procedures, restrictions and willingness to 
participate as evidenced by voluntary written informed consent and has received a 
signed and dated copy of the informed consent form.
2. SEX / AGE
Female aged between 18 and 45years inclusive.
3. GENERAL HEALTH
Good general and mental health with, in the opinion of the investigator or medically 
qualified designee no clinically significant and relevant abnormalities in medical 
history or upon physical examination.
4. COMPLIANCE
Willingness to actively participate in the study and to attend all scheduled visits.
5. SKIN TYPE
A. Minimum of 108and maximum of 25blemishes (papulesand pustules) at 
Visit 1 and a minimum of 8 blemishes (papules andpustules) at Visit 2.
B. Fitzpatrick photo-type I-V (Appendix 1SECTION6.1.4).
C. Sebumeter score of >66 µg / cm2at the forehead.
6. CONTRACEPTION
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 31 of 70

Females of childbearing potential who are, in the opinion of the investigator, 
practising a reliable method of contraception.  Adequate contraception is defined as 
abstinence, oral contraceptive, either combined or progestogen alone OR injectable 
progestogen OR implants of levonorgestrel OR estrogenic vaginal ring OR 
percutaneous contraceptive patches OR intrauterine device or intrauterine system OR 
double barrier method (condom or occlusive cap [diaphragm or cervical vault caps] 
plus spermicidal agent [foam, gel, film, cream, suppository]) OR male partner 
sterilization prior to the female subject
's entry into the study, and this male is the sole 
partner for that subject.
7. Cleansing Routine
Cleanses their face at least once a day. 
4.2. Exclusion Criteria
A subject will not be eligible for inclusion in this study if any of the following criteria 
apply:
1. PREGNANCY
Women who are known to be pregnant or who are intending to become pregnant over 
the duration of the study.
2. BREAST-FEEDING
Women who are breast-feeding.
3. CONCURRENT MEDICATION/ MEDICAL HISTORY
A. Medical history of using a medicated acne treatment (e.g. Benzoyl Peroxide, 
Clindamycin, isotretinoin) within the last 12months.
B. Change in contraception within the last 3 months.
C. Active skin disease in the test area.
D. Medical history of dysplastic nevi or melanoma on the face.
E. Moles, cysts, tattoos, scars, irritated skin, hairs, etc. at the test area that could 
influence the investigation.
F. Systemic therapy with immuno-suppressive drugs (e.g. corticosteroids) and/or 
antihistamines within 7 days prior to the start of the study and/or throughout 
the entire course of the study.
G. Systemic use of anti-microbials within the last month. 
H. Systemic use of over-the-counter (OTC) analgesics or anti-inflammatory 
drugs 24 hours prior to dosing at the first assessment visit. 
I. One of the following illnesses that might require regular systemic medication: 
Insulin-dependent diabetes, cancer.
J. One of the following illnesses if not medicated: Asthma, hypertension
K. Medical history of abnormal response to sunlight.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 32 of 70

L. History of mental illness.
M. Medically diagnosed acne vulgaris, acne conglobate, fulminans, secondary 
acne (drug induced acne) or any acne requiring systemic or topical treatment.
N. No aesthetic, cosmetic or dermatological treatment in the treatment area (face) 
within the last month. 
O. No intense sun exposure, UV-treatments or tanning salon visit within the last 
2 weeks.
4. ALLERGY/ INTOLERANCE
A. Known or suspected intolerance, allergy or hypersensitivity to study materials 
(or closely related compounds) or any of their stated ingredients.
B. History of allergies to cosmetic products ormedicated acne treatments.
5. CLINICAL STUDY/ EXPERMENTAL PRODUCT
A. Participation in another clinical study (including cosmetic studies) or receipt 
of an investigational drug within 30days of the screening visit.
B. Previous participation in this study.
6. SUBSTANCE ABUSE
Recent history (within the last 5 years) of alcohol or other substance abuse.
7. PERSONNEL
An employee of the sponsor or the study site or members of their immediate family.
4.3. Screening/ Baseline Failures
Screen failures are defined as subjects who consent to participate in the study but are 
never subsequently randomised.  In order to ensure transparent reporting of screen 
failure subjects, a minimal set of screen failure information is required including 
Demography, Screen Failure details, Eligibility Criteria, and any Serious Adverse 
(SAEs) Events. Re-screening of subjects will not be allowed in this study.
ON 5 MAY 2017 THE SPONSOR AGREED TO RELAX THE SCREENING 
CRITERIA TO ENABLE THE INCLUSION OF SUBJECTS WITH A 
MINIMUM OF 8 FACIAL BLEMISHES TO FACILITATE RECRUITMENT. 
SUBJECTS WHO PREVIOUSLY SCREEN-FAILED BECAUSE OF THIS 
CRITERIA WILL BE ELIGIBLE FOR RE-SCREENING. SUBJECTS WHO 
WERE SCREEN FAILURES FOR OTHER REASONS WILL NOT BE 
ELIGIBLE FOR RE-SCREENING.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 33 of 70

4.4. Withdrawal/ Stopping Criteria
A subject may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioural or 
administrative reasons.
If the reason for removal of a subject from the study is an Adverse Event (AE)or an 
abnormal laboratory test result, the principal specific event or test will be recorded on 
the electronic case report form (eCRF).  If a subject is withdrawn from the study 
because of a product limiting AE, thorough efforts should be clearly made to 
document the outcome. Any AEs ongoing at the final visit will be followed up until 
resolved, the condition stabilizes, is otherwise explained, or the subject is lost to 
follow-up.
The following actions must be taken in relation to a subject who fails to attend the 
clinic for a required study visit:
1. The site must attempt to contact the subject and re-schedule the missed visit as 
soon as possible. 
2. The site must counsel the subject on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the subject wishes to 
and/or should continue in the study. 
3. In cases where the subject is deemed ‘lost to follow up’, the investigator or 
designee must make every effort to regain contact with the subject (where 
possible, at least2 telephone calls). The contact attempt should be 
documented in the subject’s record. 
4. Should the subject continue to be unreachable, only then will he/she be 
considered to have withdrawn from the study with a primary reason of “Lost 
to Follow-up”.
4.5. Subject Replacement
Subjects who withdraw from the studypost-randomisation will not be replaced. 
4.6. Subject and Study Completion
A completed subject is one who has completed all phases of thestudy.  The end of the 
study is defined ascompletion of the photographic assessments by lay graders, which 
will occur no sooner than the last subject’s last visit.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 34 of 70

5. PRODUCT INFORMATION
5.1. Study Product
The following study products will be supplied by the Clinical Supplies Department, 
GSKCH:
Washout / 
Standard 
Cleanser
Test Product
Positive 
Control 
Cleanser
Positive 
Control 
Moisturiser
Product Name 
Simple Kind 
to Skin 
Moisturising 
Facial Wash
Moisturising 
Cream with 
Niacinamide
Neutrogena 
Visibly Clear 
Spot Clearing 
Facial Wash
Vivatinell 
Acnecinamide 
Gel Cream
Product 
Formulation 
Code (MFC)
Commercially 
Available 
(UK)
Commercially 
Available 
(UK)
Commercially 
Available 
(Turkey)
Application 
Quantity
Approx. 0.6 g Approx. 0.6 g Approx. 0.6 g Approx. 0.6 g
Application 
Instructions
Use twice daily 
(morning and 
night)with at 
least 8 hours 
between 
product 
applications.
Wet your face 
and hands with 
water. Dispense 
the product into 
your hands and 
apply to the 
face. Massage 
gently. Rinse 
with water and 
pat dry.
Avoid contact 
with eyes. If 
contact occurs, 
rinse thoroughly 
with water.
Use twice daily 
(morning and 
night)with at 
least 8 hours 
between product 
applications.
Dispensetwo 
pumps of 
product onto 
your fingertips 
and apply to 
your whole 
face, covering 
all blemishes.
Avoid contact 
with eyes. If 
contact occurs, 
rinse thoroughly 
with water.
Use twice daily 
(morning and 
night)with at 
least 8 hours 
between product 
applications.
Wet your face 
and hands with 
water. Dispense 
the product into 
your hands and 
apply to the 
face. Massage 
gently. Rinse 
with water and 
pat dry.
Avoid contact 
with eyes. If 
contact occurs, 
rinse thoroughly 
with water.
Use twice daily 
(morning and 
night)with at 
least 8 hours 
between product 
applications.
Apply a pea-
sized quantity to 
your whole 
face, covering 
all blemishes.
Avoid contact 
with eyes. If 
contact occurs, 
rinse thoroughly 
with water.
Other items to be supplied by the Clinical Supplies Department, GSKCH:
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 35 of 70
CCI

Name of Item
Purpose
N/A
N/A
5.2. ApplicationSchedule
A 5-7 day washout period is included to standardize subjects’ cleansing and skin care 
regimens prior to entering the test phase. Subjects will be instructed not to use any 
skin care or cosmetic product during the washout phase and to cleanse twice a day 
(morning and night) with the washoutfacial cleanser provided(Simple Kind to Skin 
Moisturising Facial Wash; Commercially Available (United Kingdom (UK)).
Morning applications should occur prior to Noon (12:00) and evening applications 
should occur prior to midnight (00:00). Morning and evening applications shouldbe 
separated by at least 8 hours. To remain eligible for this study, subjects must 
complete the washout period (assessed at Visit 2) with at least 8 blemishes (papules 
and pustules, excluding the nose).
Following the washout period, subjects who continue to be eligible for the study will
be randomised to one of three treatment regimens (no-treatment + standardcleanser,
test product+ standardcleanser,or positive controlcream + positive control 
cleanser).
During the test phase, subjects randomised to test product or positive control regimen 
will be instructed to use the cleanser and test/control products twice a day (morning
and night).Morning applications should occur prior to Noon (12:00) and evening 
applications should occur prior to midnight (00:00). Morning and evening 
applications should be separated by at least 8 hours. Subjects will be instructed to 
apply the test product or positive control creamimmediately after cleansing. Subjects 
randomised to the no treatment regimen will use the standard cleanser (only) twice a 
day. The first application of the standard cleanser or positive control cleanser will be 
at the site,under supervision of the Investigator or designee who will provide 
instruction on how to correctly apply the product. The first application of test product 
or positive control will be conducted by the subject at the site, after cleansing, under 
the supervision of the Investigator or designee who will provide instruction on how to 
correctly apply the product. 
5.3. ApplicationModification
No modificationof product applicationis permitted in this study.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 36 of 70

5.4. Product Compliance
A daily dairy will be used to monitor and promote compliance. Subjects will not be 
excluded due to missed applications, but will be reminded to use the products as per 
the instructions provided and to complete the diary card ona daily basis. The number 
of missed or additional product applications will be recorded by the Investigator or 
designee as deviationson theelectronic Case Report Form (eCRF).
5.5. Precautions
No special precautions are required providing the study is carried out in accordance 
with this protocol.
5.6. Rescue Therapy
No rescue therapy is required in this study.
5.7. Product Assignment
Subjects will be assigned to study product in accordance with the randomisation 
schedule generated bythe Biostatistics Department, GSKCH, prior to the start of the 
study, using validated internal software.
5.7.1 Randomisation
A unique screeningnumber will identify each subject screened for study 
participation.  Screening numbers will be assigned in ascending numerical order as 
each subject signs their consent form.  Subjects who meet all inclusion and exclusion 
criteria will be randomised according to the randomisation schedule.  Randomisation 
numbers will be assigned in ascending numerical order as each subject is determined 
to be fully eligible.
5.7.2 Blinding
This is an evaluator-blindclinical study. Therefore, all personnel and evaluators who 
may influence study outcomes are blinded to the product allocation of subjects and 
their diaries. The Investigator or their designees who are not involved in procedures 
or processes which may influence study outcomes are not required to be blinded to 
the product allocation of subjects and will have visibility of the subject diary.
5.7.3 Code Breaks
The blind must only be broken in an emergency where it is essential to know which 
product a subject received in order to give the appropriate medical care.  Wherever 
possible the Investigator (or designee) must contact the Sponsor prior to breaking the 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 37 of 70

blind.  The investigator must document the reason for breaking the code and sign and 
date the appropriate document.
The study blind must be returned to GSKCH at the end of the study.
5.8. Packaging and Labelling
The contents of the label will be in accordance with all applicable regulatory 
requirements and will be the responsibility of the Clinical Supplies Department, 
GSKCH.
The Washout Cleanser (Simple Kind to Skin Moisturising Facial Wash) will be over-
wrapped in opaque vinyl and any branding on the commercial products will be 
obscured. The tubes will be supplied with a study label affixed by the Sponsor. Each 
study label will contain, but not be limited to, protocol number and directions for 
storage.
The Standard Cleanser (Simple Kind to Skin Moisturising Facial Wash) and Positive 
Control Moisturiser (Vivatinell Acnecinamide Gel Cream) will be over-wrapped in 
opaque vinyl and any branding on the commercial products will be obscured. The 
tubes will be supplied with a study label affixed by the Sponsor. Each study label will 
contain, but not be limited to, protocol number, study regimen code and directions for 
storage.
The Test product ( 
) will be supplied in pump tubes with a study label 
affixed by the Sponsor. Each study label will contain, but not be limited to, protocol 
number, study regimen code and directions for storage.
The Positive Control Cleanser (Neutrogena Visibly Clear Spot Clearing Facial Wash) 
will be supplied in commercial packs that will be over-wrapped with opaque vinyl to 
obscure anycommercial branding as much as possible. The bottles will be supplied 
with a study label affixed by the Sponsor. Each study label will contain, but not be 
limited to, protocolnumber, study regimen code and directions for storage.
Care should be taken with the supplied products and their labels so that they are 
maintained in good condition.  It is important that all labels remain intact and legible 
for the duration of the study. 
5.8.1. Accountability of Product
All products supplied are for use only in this clinical study and should not be used for 
any otherpurpose.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 38 of 70
CCI

The investigator or designee will maintain a full record of study product 
accountability. A product dispensing log must be kept current and will contain the 
following information:
1. The identification of the subject to whom the study product was dispensed.
2. The date(s) and quantity of the study product dispensed to the subject.
3. The date(s) and quantity of the study product returned by the subject (if 
applicable).
The inventory must be available for inspection by the study monitor during the study.
At the end of the study, study product supplies will be verified by the monitor.  Study
 
product supplies will then be either collected by the study monitor or returned by the 
investigator or designee to the GSKCH Clinical Supplies Department or designated
vendor.
5.8.2. Storage of Product
Study product supplies must be stored in compliance with the label requirements in a 
secure place with limited or controlled access.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 39 of 70

6. STUDY ASSESSMENTS AND PROCEDURES
This section lists the procedures and parameters of each planned study assessment.  
The exact timing of each assessment is listed in the Schedule of Events section.
Adherence to the study design requirements, including all assessments and 
procedures are essential and required for study conduct.
6.1. Visit 1 / Day -7 to Day -5–Screening/Washout Visit
6.1.1. Informed Consent
Prior to execution of any study procedure, the investigator, or designee, must obtain 
written (signed and dated by the subject) informed consent from each subject 
participating in this study after adequate explanation of the aims, methods, objectives, 
and potential hazards of the study.To be considered eligible for this study, subjects 
must provide their consent to permit use of photographic images of their face for 
assessment/grading after their final visit to the study site.
The investigator, or designee, must also explain to the subjects that they are 
completely free to refuse to enter the study or to withdraw from it at any time.  
Appropriate forms for documenting a written consent will be provided by the 
investigator or by GSKCH.  The investigator, or designee, should sign and date the 
consent form to confirm that the consent process was completed correctly.  The 
subject will be provided with a copy of their signed and dated consent form and any 
other written information which they should be instructed to retain.
If, during a subject’s participation in the study, any new information becomes 
available that may affect the subject’s willingness to participate in the study, each 
ongoing subject should receive a copyof this new information and be re-consented 
into the study. Subjects should be provided with a copy of the signed and dated 
amended consent form. The date of consent will be recorded on the eCRF.
6.1.2. Demographics
The following demographic parameters will be captured by the Investigator or
designee and recorded on the eCRF: year of birth, gender, Fitzpatrick skin type and 
race.
6.1.3. Medical History and Concomitant Medication
Medical history will be assessed as related to the inclusion/exclusion criteria by the 
Investigator or designee.  Details of any relevant medical or surgical history within 
the last year, including allergies or drug sensitivity, will be recorded on the eCRF.  
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 40 of 70

Any concomitant therapy taken in the 30 days prior to the Screening Visit and 
throughout the study will also be recorded.
6.1.4. Fitzpatrick Skin Type Assessment
Fitzpatrick skin type assessment will be conducted by atrained and qualified 
investigator and recorded on the eCRF using the scale below.
6.1.5. Evaluator Assessment of BlemishCounts
The following assessment will be conducted by a trainedand qualifiedevaluator 
reflective of the subject’s facial skin condition at the time of the evaluation and 
recorded on the eCRF.  All practical efforts will be made to ensure the sameblinded
evaluator assesses the same subject through the entire study.
Forehead
Cheeks
Chin
Sub Total
Papules
#
#
#
#
Pustules
#
#
#
#
Sub Total
#
#
#
#
# = Number ofpapules or pustules
THE GRAND TOTAL OF THE NUMBER OF PAPULES AND PUSTULES AT 
THE FOREHEAD, CHEEKS AND CHIN WILL BE AUTOMATICALLY 
CALCULATED ON THE CRF AT VISITS 1 AND 2 TO PROVIDE CLARITY 
ON SUBJECT COMPLIANCE WITH INCLUSION CRITERION 5A.
6.1.6.Forehead Sebumeter Measurements
A blind, trained and qualified evaluator will conduct instrumental measurements of 
skin sebum levels. Subjects willfirst acclimatize to the controlled room temperature 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 41 of 70
CCI

(21±1 ºC) and humidity (50±10%RH) for at least 30 minutes prior to instrumental 
assessment.Subject visits should be scheduled at similar times of day.
6.1.7. Inclusion / Exclusion Criteria
Inclusion/exclusion criteria will be assessed by the Investigator or designee and 
recorded on theeCRF.
6.1.8. Subject Eligibility
Subjects meeting the inclusion and exclusion criteria, whom provide their informed 
consent and who are otherwise considered eligible for enrollment in the studybythe 
Investigator or medically qualified designee will be enrolled into the study.
Confirmation of whether a subject was enrolled, or not, will be recorded on the eCRF.
6.1.9. WashoutProductand Diary Dispensing
Dispensing of washout product and diary to subjects to standardize skin care regimen 
and usage instructions will be recorded on the eCRF.
6.2. Visit 2/ Day 1–BaselineVisit
6.2.1. Current / Concomitant Medication
Any concomitant therapy taken since the last visit and throughout the study
 will be 
recorded on the eCRF by the Investigator or designee.
6.2.2. Diary Review (Compliance)
Subject diaries will be reviewed by the Investigator or their designee. The total 
number of missedand additionalwashout cleanserapplications will be recorded on 
the eCRF.Subjects who apply the washout cleanser more or less frequently than 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 42 of 70
CCI

twice a day will be considered to have deviated from the protocol and 
additional/missed applications will recorded on the Deviations Logon the eCRF. 
6.2.3. Continued Eligibility
The Investigator or designee will ascertain whether there have been any deviations 
from the protocol since the last visit, whether the subject has adhered to the lifestyle 
restrictions since the last visit and whether, in their opinion, the subject is eligible to 
continue in the study. Subject continued eligibility will be recorded on the eCRF.
6.2.4. Evaluator Assessment of BlemishCounts
Assessment will be conducted as per 6.1.5
6.2.5. Inclusion / Exclusion Criteria
Inclusion/exclusion criteria detailed in Appendix 2will be assessed by the 
Investigator or designee to confirm subject eligibility and recorded on the eCRF. 
Subjects who trigger any of the exclusion criteria will be discharged from the study. 
6.2.6. Subject Eligibility
Subjects meeting the inclusion and exclusion criteriadetailed in Appendix 2and who 
are otherwise considered eligible to continue in the study by the Investigator or 
medically qualified designee will be randomised. Confirmation of whether a subject 
was randomised, or not, will be recorded on the eCRF.
6.2.7. Randomisation
Subject randomisation will be conducted as per the process detailed in Section 5.7.1 
and documented on the eCRF.
6.2.8. Image Capture
High resolution colour photographs of the front of each subject’s face will be taken 
usinga Canfield Visia imaging system, using polarised and non-polarisedlighting.  
Jewelry will be removed and hair loosely tied back and covered with a black veil so 
that it does not interfere with the photograph. Subjects will be asked to maintain a 
relaxed, neutral expression with their eyes closed. The imaging system willbe 
calibrated to ensure consistent image illumination and capture. The technician 
responsible for taking photographs must have sufficient experience and/or training to 
be capable of ensuring consistent alignment of subjects between visits. Photographic 
data will be stored in raw, uncompressed file format. The same imaging system will 
be used to take all photographs.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 43 of 70

Photographic images of subjects are considered personal identifiable information 
(PII) and will be transferred securely from the site to GSK.Prior to transfer to GSK, 
the site will anonymize all images by placing a black box over the eyes of the subjects 
without obscuring any facial blemishes (excluding the nose).
6.2.9. Forehead Sebumetry Measurements
Sebumetry measurements will be taken as per 6.1.6.
6.2.10. Corneometry Measurements
6.2.11. Sebumeter Kinetic Measurements
6.2.12. Washout CleanserReturn and Test Product Dispensing
The washout cleanser will be returned by all subjects. Subjects randomised to the test
productregimen will be dispensed the standard cleanser (Simple Kind to Skin 
Moisturising Facial Wash) and the test product. Subjects randomised to the positive 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 44 of 70
PPD
PPD

control regimen will be dispensed the positive control facial wash (Neutrogena 
Visibly Clear Spot Clearing Wash) and cream (Vivatinell Acnecinamide Gel Cream).
Subjects randomised to the no-treatment regimen will be dispensed standard cleanser 
(Simple Kind to Skin Moisturising Facial Wash) only.The time and date of washout 
cleanser return and productsdispensing will be documented on the eCRF. The 
Investigator or designee involved in product dispensing must not be involved in any 
assessments in order to protect the blind.
6.2.13. Supervised Product Application
Subjects randomised to the test product regimen will undergo supervised application 
of the standard cleanser and test product. Subjects randomised to the positive control 
regimen will undergo supervised application of the positive controlcleanser and 
positive controlcream. Subjects randomised to the no-treatment regimen will undergo 
supervised application of the standard cleanser, only. The Investigator or designee 
will oversee application of the product. Product application will be recorded on the 
eCRF and subject diary. The Investigator or designee involved in this step must not 
be involved in any assessments in order to protect the blind.
6.2.14. Acute Corneometer Measurements
Corneometer measurements will be taken as per 6.2.10, 1 hour ± 15 MINUTES, 3 
hours± 15 MINUTESand 8 hours ± 15 MINUTESafter test product or positive 
control creamapplicationfor subjects randomised to the test product or positive 
control regimen. Subjects randomised to the no treatment regimen will undergo 
Corneometer measurements 1hour± 15 MINUTES, 3 hours± 15 MINUTESand 8 
hours ± 15 MINUTESafter application of the standard cleanser.
6.2.15. Adverse Events
Adverse events will be assessed by a blinded investigator and recorded on the eCRF, 
as per the process detailed in Section7.
6.3. Visit 3/ Day 8 –1 Week of Application
6.3.1. Current / Concomitant Medication
To be completed as per 6.2.1
6.3.2. Diary Review (Compliance)
Subject diaries will be reviewed by the Investigator or their designee. The total 
number of missedand additionalstandard cleanser, positive control cleanser, test 
product and/or positive control applications, as appropriate per subject randomisation,
will be recorded on the eCRF.Subjects who applyeach of their allocated products 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 45 of 70

more or less frequently than twice a day will be considered to have deviated from the 
protocol and additional/missed applications will recorded on the Deviations Logon 
the eCRF. 
6.3.3. Continued Eligibility
To be completed as per 6.2.3
6.3.4. Evaluator Assessment of BlemishCounts
Assessment will be conducted as per 6.1.5
6.3.5. Sebumetry Measurements
Measurements will be taken as per 6.1.6
6.3.6. Corneometry Measurements
Measurements will be taken as per 6.2.10
6.3.7. Sebumeter Kinetic Measurements
Measurements will be taken as per 6.2.11
6.3.8. Supervised Product Application
To be completed as per 6.2.13
6.3.9. Adverse Events
To be completed as per 6.2.15
6.4. Visit 4/ Day 29–4 Weeks of Application
6.4.1. Current / Concomitant Medication
To be completed as per 6.2.1
6.4.2. Diary Review (Compliance)
To be completed as per 6.3.2
6.4.3. Continued Eligibility
Tobe completed as per 6.2.3
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 46 of 70

6.4.4. Evaluator Assessment of BlemishCounts
Assessment will be conducted as per 6.1.5
6.4.5. Sebumetry Measurements
Measurements will be taken as per 6.1.6
6.4.6. Corneometry Measurements
Measurements will be taken as per 6.2.10
6.4.7. Sebumeter Kinetic Measurements
Measurements will be taken as per 6.2.11
6.4.8. Supervised Product Application
To be completed as per 6.2.13
6.4.9. Adverse Events
To be completed as per 6.2.15
6.5. Visit 5/ Day 57–8 Weeks of Application
6.5.1. Current / Concomitant Medication
To be completed as per 6.2.1
6.5.2. Diary Review (Compliance)
To be completed asper 6.3.2
6.5.3. Continued Eligibility
To be completed as per 6.2.3
6.5.4. Evaluator Assessment of BlemishCounts
Assessment will be conducted as per 6.1.5
6.5.5. Image Capture
Measurement will be taken as per 6.2.8
6.5.6. Sebumetry Measurements
Measurements will be taken as per 6.1.6
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 47 of 70

6.5.7. Corneometry Measurements
Measurements will be taken as per 6.2.10
6.5.8. Sebumeter Kinetic Measurements
Measurements will be taken as per 6.2.11
6.5.9. Test Product, Cleanser and Diary Return
Standard cleanser, positive control cleanser, positive control cream, test product and 
subject diary will be returned to the Investigator or designee and documented on the 
eCRF. 
6.5.10.Adverse Events
To be completed as per 6.2.15
6.5.11. Lay Person Assessment of Overall Appearance of Blemishes 
(Photographs)
The baseline and week 8 photographs of test subjects will be displayed side by side 
on a high resolution, colour-calibrated display screen in a room with neutral wall 
colours and standardised lightingand all practical effortswill be made to minimize 
glare. The relative positioning (left and right) of the baseline and week 8 photographs 
will be blinded to the evaluator and randomised.The randomisation schedule for the 
image pair assessments will be generated by GSK.  A technician will use the 
randomisation schedule to display each pair of images to each lay evaluator. Both the 
polarised and non-polarised image pairs will be assessed for every subjectby every 
lay evaluator.Lay evaluators will be blind to the identity of each image. 
24 blinded,lay evaluatorswill assess the baseline and week 8 images to judge the 
magnitude of improvement in overall appearance of blemishes using the below scale. 
The evaluators’scoreswill be recorded on the eCRF.
Score
Description
Left
The blemishes in the image on the left are more obvious than those in the 
image on the right
Right
The blemishes in the image on the right are more obvious than those in the 
image on the left
The lay evaluators will come to the study site on image assessment days and will be 
informed about the assessment and will give their written informed consent to 
participate, which includes the following inclusion/exclusion criteria (Inclusion: 18 to 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 48 of 70

70 years; knowledge how to use a computer;Exclusion: problems with the eyes; 
change of lenses or glasses within the last 7 days before the start of the study; 
migraine or headache on the assessment day). The lay evaluators will have subject 
identification numbers (IDs)and their participation in the study will be recorded.
The lay evaluators will be recruited by the site. Once the ‘lay evaluator’ Informed 
Consent is signed, the site will explain the imaging assessment process (2 images on 
the same screen that have to be ranked). A paper source document will be used to 
record the lay evaluator response for each image pair and this will be transcribed into 
the eCRF bythe Investigator or designee. 
6.5.12. Discharge from Study
Subjects will be evaluated to determine if they completed all study procedures or if 
they were discontinued from the study early.  If the subject discontinued at any point 
during the study, the primary reason for withdrawal should be recorded on the Study 
Conclusion page of the eCRF by selecting one of the options below.
1.
Subject did not meet study criteria
2.
Adverse Event
3.
Lostto Follow Up
4.
Protocol Violation
5.
Withdrawal of Consent
6.
Other
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 49 of 70

7. SAFETY ASSESSMENTS
7.1. Definitions of an Adverse Event and Serious Adverse Event 
7.1.1. Adverse Events
The investigator or site staff will be responsible for detecting, documenting and 
reporting events that meet the definition of an AE or SAE.
Adverse Event Definition:
1. An AE is any untoward medical occurrence in a subjector clinical 
investigation subject, temporally associated with the use of an investigational 
or washout product, whether or not considered related to the investigational or 
washout product.
2. NOTE: An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease (new or 
exacerbated) temporally associated with the use of an investigational or 
washout product.
Events meeting AE definition include:
1. Any abnormal laboratory test results (if applicable) or other safety 
assessments, including those that worsen from baseline, and felt to be 
clinically significant in the medical and scientific judgment of the 
investigator.
2. Exacerbation of a chronic or intermittent pre-existing condition including 
either an increase in frequency and/or intensity of the condition.
3. New condition(s)detected or diagnosed after study product administration 
even though it may have been present prior to the start of the study.
4. Signs, symptoms, or the clinical sequelae of a suspected interaction.
5. Signs, symptoms, or the clinical sequelae of a suspected overdose of either 
study product or a concomitant medication (overdose per se will not be 
reported as an AE/SAE).
Events NOT meeting definition of an AE include:
1. Any clinically significant abnormal laboratory findings (if applicable) or other 
abnormal safety assessments which are associated with the underlying disease, 
unless judged by the investigator to be more severe than expected for the 
subject’s condition. 
2. The disease/disorder/ condition being studied or expected progression, signs, 
or symptoms of the disease/disorder being studied, unless more severe than 
expected for the subject’s condition.. 
3. Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition 
that leads to the procedure is an AE.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 50 of 70

4. Situations where an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).
5. Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen.
7.1.2. Serious Adverse Events
Serious Adverse Event is defined as any untoward medical occurrence that, at 
any dose:
A. Results in death
B. Is life-threatening
NOTE: The term 
'life-threatening
' in the definition of 
'serious
' refers to an 
event in which the subject was at risk of death at the time of the event.  It does 
not refer to an event, which hypothetically might have caused death, if it were 
more severe.
C. Requires hospitalization or prolongation of existing hospitalization
NOTE: In general, hospitalization signifies that the subject has been detained 
(usually involving at least an overnight stay) at the hospital or emergency 
ward for observation and/or treatment that would not have been appropriate in 
the physician’s office or out-patient setting.  Complications that occur during 
hospitalization are AEs.  If a complication prolongs hospitalization or fulfills 
any other serious criteria, the event is serious.  When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered 
serious.
Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE.
D. Results in disability/incapacity
NOTE: The termdisability means a substantial disruption of a person’s ability 
to conduct normal life functions.
This definition is not intended to include experiences of relatively minor 
medical significance such as uncomplicated headache, nausea, vomiting, 
diarrhea, influenza, and accidental trauma (e.g. sprained ankle) which may 
interfere or prevent everyday life functions but do not constitute a substantial 
disruption.
E. Is a congenital anomaly/birth defect
F. Other Situations
1. Medical or scientific judgment should be exercised in deciding 
whether reporting is appropriate in other situations, such as important 
medical events that may not be immediately life-threatening or result 
in death or hospitalization but may jeopardize the subject or may 
require medical or surgicalintervention to prevent one of the other 
outcomes listed in the above definition. These should also be 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 51 of 70

considered serious.
2. Examples of such events are invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, 
blood dyscrasias or convulsions that do not result in hospitalization or 
development of drug dependency or drug abuse or reports of 
spontaneous abortion.
7.2. Recording Adverse Events and Serious Adverse Events
Recording of adverse events and serious adverse events:
1. The investigator or site staff will be responsible for detecting, documenting 
and reporting events that meet the definition of an AE or SAE. 
2. The investigator or site staff will then record all relevant information 
regarding an AE/SAE in the CRF.
3. There may be instances when copies of medical records for certain cases are 
requested by GSK.  In this instance, all subject identifiers, with the exception 
of the subject number, will be blinded on the copies of the medical records 
prior to submission to GSK.
4. The investigator will attempt to establish a diagnosis of the event based on 
signs, symptoms, and/or other clinical information.  In such cases, the 
diagnosis will be documented as the AE/SAE and not the individual 
signs/symptoms. Clinical AEs will be described by diagnosis and not by 
symptoms when possible (e.g., upper respiratory tract infection, seasonal 
allergy, etc. instead of runny nose).
5. AEs will be collected from thestart of the washout product and until 5 days 
following last administration of the study product.
6. SAEs will be collected over the same time period as stated above for AEs.  
However, any SAEs assessed as relatedto study participation (e.g., 
investigational product, protocol mandated procedures, invasive tests, or 
change in existing therapy) or related to a GSK concomitant medication will 
be recorded from the time a subject consents to participate in the study up to 
and including any follow-up contact.  
7. Medical conditions reported prior to the time period for reporting AEs/SAEs 
should be recorded as part of the subject’s medical history.
7.3. Evaluating Adverse Events and Serious Adverse Events
Assessment of Intensity:
The investigator or designee will make an assessment of intensity for each AE and 
SAE reported during the study and will assign it to one of the following categories:
1. Mild:  An event that is easily tolerated by the subject, causing minimal 
discomfort and not interfering with everyday activities.
2. Moderate:  An event that is sufficiently discomforting to interfere with normal 
everyday activities
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 52 of 70

3. Severe:  An event that prevents normal everyday activities. An AE that is 
assessed as severe will not be confused with an SAE. Severity is a category 
utilized for rating the intensity of an event; and both AEs and SAEs can be 
assessed as severe.
Note: An event is defined as ‘serious’ when it meets at least one of the pre-defined 
outcomes as described in the definition of an SAE.
Assessment of Causality:
1. The investigator is obligated to assess the relationship between study product 
and the occurrence of each AE/SAE.
2. A "reasonable possibility" is meant to convey that there are facts/evidence or 
arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out.
3. The investigator will use clinical judgment to determine the relationship.
4. Alternative causes, such as natural history of the underlying diseases, 
concomitant therapy, other risk factors, and the temporal relationship of the 
event to the study product will be considered and investigated.
5. The investigator will also consult the Investigator Brochure (IB) and/or 
Product Information, for marketed products, in the determination of his/her 
assessment.
6. For each AE/SAE the investigator must document in the medical notes 
(source document) or CRF that he/she has reviewed the AE/SAE and has 
provided an assessment of causality.
7. There may be situations when an SAE has occurred and the investigator has 
minimal information to include in the initial report to GSK.  However, it is 
very important that the investigator always make an assessment of 
causality for every event prior to the initial transmission of the SAE data 
to GSK.
8. The investigator may change his/her opinion of causality in light of follow-up 
information, amending the SAE data collection tool accordingly.
9. The causality assessment is one of the criteria used when determining 
regulatory reporting requirements.
7.4. Reporting Adverse Events and Serious Adverse Events
AE Reporting to GSKCH:
1. AEs willbe recorded in the AE section of the CRF. 
2. Medical conditions recorded by the subject on a diary
 card or similar 
document that meet the definition of an AE must also be recorded in the AE 
section of the CRF, if not previously well-characterized by the investigator in 
the subject’s medical history. 
3. AEs elicited by the investigator in a standard manner at the study visits should 
also be recorded in the AE section of the CRF.  The investigator or designee 
must ask the subject the following question during each visit including any 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 53 of 70

follow-up visits:  “Have you felt unwell, experienced any symptoms or taken 
any medication (since your last visit) (today) (since your last dose) (since the 
last session)?”
4. The medically qualified investigator should review adverse events in a timely 
manner; this review should be documented in writing in the source document 
or in the CRF. 
5. After the study is completed at a given site, and the site has received their 
study data on Compact Discs (CDs), the electronic data collection tool will be 
removed from the internet to prevent the entry of new data or changes to 
existing data.
SAE Reporting to GSKCH:
A paper copy of the SAE form provided in the investigator study master file should 
be completed as fully as possible. 
It is essential to enter the following information: 
1. Protocol and subject identifiers
2. Subject’s demography
3. Description of events, with diagnosis if available
4. Investigator opinion of relationship to study product (see section 8.3)
5. Criterion for seriousness.
The following are desirable and are of particular relevance for investigator and 
GSKCH assessment of the SAE report:
1. Date of onset of AE 
2. Date AE stopped, if relevant
3. Study product start date
4. Study product end date if relevant
5. Action taken on study product
6. Outcome if known
The SAE form, completed as fully as possible, and SAE fax cover sheet must be 
faxed or e-mailed to the appropriate GSKCH Study Manager as soon as possible, but 
not later than 24 hoursafter study site personnel learn of the event. The GSKCH 
Study Manager should be notified of the situation by telephone or email.
Fax Serious Adverse Events to:
The GSKCH SAE Coordinator will be responsible for forwarding the SAE form to 
the Case Management Group, Global Clinical Safety and Pharmacovigilance, the 
Medical Director responsible for the study and other GSKCH personnel as 
appropriate via email.
Brazil SAE Coordinator (
):
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 54 of 70
PPD
PPD

Tel: 
E-mail: 
Brazil backup contact (
):
Tel: 
Email:
The initial report will be followed up with more information as relevant, or as 
requested by the GSKCH study manager.
7.5. Follow-up of Adverse Events and Serious Adverse Events
Follow-up of AEs and SAEs:
1. After the initial report, the investigator is required to proactively follow up 
with each subject and provide further information on the subject’s condition.
2. All AEs/SAEs will be followed until resolution, until the condition stabilizes, 
until the event is otherwise explained, or until the subject is lost to follow-up.  
3. The investigator is obligated to perform or arrange for the conduct of 
supplemental measurements and/or evaluations as may be indicated or as 
requested by GSK to elucidate as fully as possible the nature and/or causality 
of the AE or SAE.
4. Investigators are not obliged to actively seek AEs or SAEs in former subjects.  
However, if the investigator learns of any SAE, including the death, at any 
time after a subject hasbeen discharged from the study, and considers the 
event reasonably related to the investigational product or study participation, 
the investigator will promptly notify GSKCH.
5. The investigator will submit any updated SAE data to GSK within the 
designated reporting time frames.
Regulatory and ethics reporting requirements for SAEs:
1. The investigator will promptly report all SAEs to GSKCH within the 
designated reporting timeframes (within 24 hours of learning of the event).  
GSKCH has a legal responsibilityto notify, as appropriate, the local 
regulatory authority and other regulatory authorities about the safety of a 
product under clinical investigation.  Prompt notification of SAEs by the 
investigator to GSKCH is essential so that legal obligations and ethical 
responsibilities towards the safety of subjects are met.
2. GSKCH will comply with country specific regulatory requirements relating to 
safety reporting to the regulatory authority, IECand investigators.
3. Investigator safety reports are prepared according to GSKCH policy and are 
forwarded to investigators as necessary.  An investigator safety report is 
prepared for a SAE(s) that is both attributable to investigational product and 
unexpected.  The purpose of the report is to fulfill specific regulatory and
GCP requirements, regarding the product under investigation.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 55 of 70
PPD
PPD
PPD
PPD
PPD

4. An investigator who receives an investigator safety report describing a SAE(s) 
or other specific safety information (e.g., summary of listing of SAEs) from 
GSKCH will file it with the Investigator Brochure (or safety statement) and 
will notify the IEC, if appropriate according to local requirements.
7.6. Collection of Pregnancy Information
7.6.1. Time Period for Collecting of Pregnancy Information
Collection of Pregnancy Information:
1. Pregnancy information will be collected on all pregnancies reported following 
administration of any washout product. Information on pregnancy identified 
during the screening phase and prior to washout product administration does 
not need to be collected.
7.6.2. Action to be Taken if Pregnancy Occurs
Action to be Taken:
1. The investigator will collect pregnancy information on any subject who 
becomes pregnant while participating in the study after administration of the 
washout product. The investigator will recordpregnancy information on the 
appropriate form and submit it to GSKCH within 2 weeks of learning of the 
subject becoming pregnant. The subject will be followed to determine the 
outcome of the pregnancy. Information on the status of the mother and infant / 
neonate (including concomitant medications taken by the mother during the 
pregnancy) will be forwarded to GSKCH. Generally, follow-up will be no 
longer than 6 to 8 weeks following the estimated delivery date. Any 
termination of the pregnancy will be reported.
2. While pregnancy itself is not considered to be an AE, any pregnancy 
complication or elective termination for medical reasons will be recorded as 
an AE or SAE.
3. A spontaneous abortion is always considered to be an SAE and will be 
reported as such. An SAEoccurring in association with a pregnancy, brought 
to the investigator’s attention after the subject completed the study and 
considered by the investigator as possibly related to the investigational 
product, must be promptly forwarded to GSK.
4. While the investigator is not obliged to actively seek this information in 
former study participants, he or she may learn of an SAE through spontaneous 
reporting.
5. There is no requirement for the subject to be withdrawn from the study as a 
result of the pregnancy.  However if they are withdrawn, this should be 
recorded in the appropriate section of the CRF.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 56 of 70

8. DATA MANAGEMENT
For this study subject data will be entered into an electronic case report form, using a 
GSKCH validated data system.
8.1. Source Documents/ Data
The source documents (e.g. clinical and office charts, laboratory notes, memoranda, 
subjects’ diaries or evaluation checklists, dispensing records, recorded data from 
automated instruments, microfiches, photographic negatives, microfilm or magnetic 
media, subject files and records kept at the laboratory departments involved in the 
clinical study) which contain the source of data recorded in the eCRF should be 
specified in the Source Document Designation Form.  In some cases the eCRF can be 
used as a source document.
Each subject will be assigned and identified by a unique Screening Number. Any 
reference made to an individual subject within the study must be done using the 
unique Screening Number.
8.2. Electronic Case Report Form
AneCRF is an electronic document designed to record all of the protocol required 
information to be reported to the sponsor on each trial subject.
For each subject who has given informed consent/assent and has been screened, an 
eCRF must be completed and signed by the Principal Investigator (or authorized 
designee) to certify that the data are complete and correct.  
Management of clinical data will be performed in accordance with applicable 
GSKCH standards and data cleaning procedures to ensure the integrity of the data e.g. 
removing errors and inconsistencies in the data. 
In order to protect the privacy of subjects, no Personally Identifiable Information 
(including the subject
's name or initials or birth date) is to berecorded in the CRF or 
as part of the query text.
Adverse events and concomitant medications terms (if applicable) will be coded 
using MedDRA (Medical Dictionary for Regulatory Activities) and an internal 
validated medication dictionary, GSKDrug.  
Subject data will be entered into GSKCH defined eCRFs and transmitted 
electronically to GSKCH in a validated (21 CFR Part 11 compliant) web-based 
electronic data capture system (InForm
TM).
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 57 of 70

All eCRF pages should be completed during a subject assessment when the eCRF has 
been designated as the source.  Data that is sourced elsewhere should be entered into 
the eCRF in an agreed upon timeframe between the Investigator and Sponsor.  
The eCRFs (including queries, query responses and audit trails) will be retained by 
GSKCH. Site data archived CDsprepared by a third party will be sent to the 
investigator to maintain as the investigator copy following the decommissioning of 
the study.
8.3. Data Handling
Documentation of all data management activities should allow step-by-step 
retrospective assessment of data quality and study performance. Any changes or 
corrections to data will be performed in the Electronic Data Capture (EDC) System, 
and it will include rationale for changes. The EDC system has an audit trail, which 
will provide a complete record of the changes and corrections endorsed by the 
Investigator.
8.3.1. Data Queries
Programmed edit checks will be generated automatically, as the data is being entered 
into the system. Data Management will also run reports and listings on the eCRF data, 
in addition to the queries already programmed and generated by the system, to raise 
manual queries as needed for site clarification or correction. The Clinical Dictionary 
Development and Management Group will raise queries as needed on safety data to
code the terms (Adverse Events and Drugs) are reported appropriately. 
The study monitor at the study site will review the eCRFs in accordance with the 
monitoring plan, and any queries will be generated in the EDC System to the 
Investigator or designee, enabling the errors to be addressed in parallel with Data 
Management review. Monitor can also run reports and listings on the eCRFs, to raise 
manual queries as needed for site clarification or correction.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 58 of 70

9. STATISTICAL CONSIDERATIONS AND DATA 
ANALYSES
9.1 Sample Size Determination
Approximately 200female subjects aged 18-45 with self-assessed sensitive skin and a 
minimum of 108and a maximum of 25 facialblemishes (papules and pustules, 
excluding the nose)will be screened to randomise 132 healthy subjects, to ensure 
approximately 40 subjects in the test productregimen,40 subjects in the no treatment 
regimen and 40 subjects in the positive control regimencomplete the study 
(Assuming a 10% dropout rate). Randomisationwill be stratified by age (<21 years 
old, >21 years of age).  
The sample size was based on clinical considerations. In a previous study of a 
cosmetic product, counts of papules and pustules decreased from a baseline mean of 
27.6 to a mean of 13.5 at Week 8 (ref. Shalita 1995 IJD). With 40 subjects in both the 
test product and no-treatment regimens,a difference between groups at least 60% the 
magnitude of the standard deviation (assumed equal for both groups) would be 
detectable at two-sided alpha=0.05 with approximately 80% power.
9.2. General Considerations
Statistical testing for the endpoints in this study will be conducted at unadjusted two-
sided alpha=0.05. While for this proof of conceptstudy statistical significance 
(p<0.05) may not be achieved, these results will drive sample size projections for 
future studies.Due to the exploratory nature of the study, no adjustment to the alpha 
level for multiple comparisons will be made.P-values resulting from inferential 
testing will be considered primarilyas summary statistics.
No statistical comparisons between the positive control regimen and the test product 
regimen are planned. The positive control is included to provide internal validation to 
the trial and to provide a reference point for estimates of effect size.
9.2.1. Definition of Analysis Populations
The ‘Intent to treat’(ITT) population includes all subjects who are randomised into 
the study and have at least one post-baselinemeasurement available. All efficacy 
analyses will be based on the ITT population.
The Per Protocol (PP) population will consist of the subset of ITT subjects which 
excludes those subjects with significant protocol deviations. Protocol deviations will 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 59 of 70

be identified prior to database unblinding and will include, but not be limited to, non-
compliance with the protocol or product application and use of prohibited 
concomitant medications. Confirmatory analyses of at least the primary efficacy 
endpoint will be performed on the PP population.
The Safety population will include all subjects who applied any of the studyproducts. 
All safety analyses will be performed using the Safety population.For the no 
treatment regimen, this will include any use of the cleanser post-randomisation.
9.2.2. Exclusion of Data from Analysis
No data will be excluded from any analysis.
9.2.3. Criteria for Evaluation
The primary objective will be to assess the skin moisturisation potentialof the test 
product formulation compared to no treatment based on change from baseline in 
corneometry8 hours after the first application of test product. Given this proof of 
concept study, the study will be considered a success if at least a trend in favor of the 
test productis observed. Other efficacy evaluations will be similarly assessed for 
success.
9.2.4. Handling of Dropouts and Missing Data
Missing data will not be replaced or imputed. Dropouts will be included in analyses 
up to the point of discontinuation.
9.3. Statistical Methods and Analytical Plan
Additional details of the proposed statistical analysis will be documented in the 
statistical analysis plan (SAP), which will be written following finalization of the 
protocol and prior to study unblinding / analysis (as appropriate).
9.3.1. Demographic and Baseline Characteristics
Age and baseline characteristics (corneometry, blemish counts, sebumetry) will be 
summarised descriptively by treatment regimen (test product, positive control, no 
treatment) using means, medians and standard deviations. Race and Fitzpatrick Skin 
Type will be summarised by treatment regimen using frequency counts and 
percentages.
9.3.2. Primary Analysis(es)
The primary endpoint is the change from baseline in Corneometermeasurement at 8 
hours following the first product application (use of cleanser for the no treatment 
regimen). Data for the endpoint will be summarized by age stratum and treatment 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 60 of 70

regimenusing means and 95% confidence intervals and compared between treatment 
regimensusing analysis of covariance (ANCOVA) with treatment main effect, age 
stratum (<21, ≥21 years of age)and baseline measurementas covariate or Wilcoxon 
rank sum test, depending on the data distribution. Differences between least squares 
means for the test product and no treatment regimen will be presented, together with 
95% confidence intervals. 
9.3.3. Secondary Analysis(es)
The change from baseline in Corneometermeasurements at 1 and 3 hours following 
the first product application as well as at Weeks 1, 4 and 8 will be summarized by age 
stratum, treatment regimen and study visit using means and 95% confidence intervals 
and compared between treatment regimensusing the ANCOVAmodel described 
above for the primary endpoint.Wilcoxon rank sum test may also be performed
depending on the data distribution. Differences between least squares means for the 
test product and notreatment regimen will be presented, together with 95% 
confidence intervals.
Sebumetry and sebum excretion rate changes from baseline at Weeks 1, 4 and 8 will 
be summarized by age stratum, treatment regimenand study visit and analyzed using 
the ANCOVAmodel described above for corneometry.Wilcoxon rank sum test may 
also be performeddepending on the data distribution. Differences between least 
squares means for the test product and no treatment regimen will be presented, 
together with 95% confidence intervals.
Clinical assessment of blemish counts (papules and pustules) will be summarized by 
age group stratum, treatment regimen and study visit and compared between 
treatmentregimens using means and 95% confidence intervals and compared between 
treatmentregimensusing the ANCOVAmodel described above for corneometry.
Wilcoxon rank sum test may also be performeddepending on the data distribution. 
Differences between least squares means for the test product and no treatment 
regimen will be presented, together with 95% confidence intervals. 
The lay person assessment resulting from the ranking of images will inherently be an 
assessment of change from baseline. As such, the data resulting from these rankings 
will be tabulated by treatment regimen as the proportion of evaluations where the 
baseline image had blemishes most obvious compared to the proportion of 
evaluations where the Week 8 image had blemishes most obvious. Data will be 
analysed using a logistic regression which will include effects of age stratum and 
treatment regimen.
9.3.4. Safety Analysis(es)
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 61 of 70

Adverse Events (AEs) will be tabulated according to the current version of the 
Medical Dictionary for Regulatory Activities (MedDRA). Frequencies and 
percentages will be presented bytreatment regimen overall, for each system organ 
class, and for each preferred term. Events specific to the face will be tabulated 
separately. Summaries of treatment-emergent AEs, treatment-related AEs, AEs 
leading to discontinuation, and serious AEs willbe completed.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 62 of 70

10. STUDY GOVERNANCE CONSIDERATIONS
10.1. Posting of Information on Publicly Available Clinical Trials 
Registers
Study information from this protocol will be posted on publicly available clinical trial
registers before enrollment of subjects begins.
10.2. Regulatory and Ethical Considerations, Including the Informed 
Consent
The study will be conducted in accordance with all applicable regulatory 
requirements, and with GSK policy.
The study will also be conducted in accordance with ICH Good Clinical Practice, all 
applicable subject privacy requirements, and the guiding principles of the current 
version of the Declaration of Helsinki.  This includes, but is not limited to, the 
following:
1. Before initiating a trial, the investigator/institution should have written and 
dated approval/favorable opinion from theIndependent Ethics Committee 
(IEC)for the trial protocol (including amendments), written informed consent 
form, consent form updates, subject recruitment procedures (e.g., 
advertisements), investigator brochure/ safety statement (including any 
updates) and any other written information to be provided to subjects. A letter 
or certificate of approval will be sent by the investigator to the sponsor prior 
to initiation of the study, and also when subsequent amendments to the 
protocol are made.
2. Signed informed consent  to be obtained for each subject before participation 
in the study (and for amendments as applicable)
3. Investigator reporting requirements (e.g. reporting of AEs/SAEs/protocol 
deviations to IEC)
4. GSK will provide full details of the above procedures, either verbally, in 
writing, or both.
10.3. Quality Control (Study Monitoring)
In accordance with applicable regulations including GCP, and GSK procedures, GSK
or designee (i.e. third party vendor) monitors will contact the site prior to the start of 
the study to review with the site staff the protocol, study requirements, and their 
responsibilities to satisfy regulatory, ethical, and GSK requirements.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 63 of 70

When reviewing data collection procedures, the discussion will include identification, 
agreement and documentation of data items for which the eCRF will serve as the 
source document.
GSK or designee will monitor the study and site activity to verify that the:
1. Data are authentic, accurate, and complete.
2. Safety and rights of subjects are being protected.
3. Study is conducted in accordance with the currently approved protocol and 
any other study agreements, GCP, and all applicable regulatory requirements.
The extent and nature of monitoring will be described in a written monitoring plan on 
file at GSKCH. The investigator (or designee) agrees to allow the monitor direct 
access to all relevant documents and agrees to co-operate with the monitor to ensure 
that any problems detected in the course of these monitoring visits are resolved.
10.4. Quality Assurance
To ensure compliance with GCP and all applicable regulatory requirements, GSK 
may conduct a quality assurance assessment and/or audit of the site records, and the 
regulatoryagencies may conduct a regulatory inspection at any time during or after 
completion of the study. 
In the event of an assessment, audit or inspection, the investigator (and institution) 
must agree to grant the advisor(s), auditor(s) and inspector(s) direct access to all 
relevant documents and to allocate their time and the time of their staff to discuss the 
conduct of the study, any findings/relevant issues and to implement any corrective 
and/or preventative actions to address any findings/issues identified.
The sponsor will be available to help investigators prepare for an inspection.
10.5. Conditions for Terminating the Study
Upon completion or premature discontinuation of the study, the GSKCH monitor will 
conduct site closure activities with the investigator or site staff, as appropriate, in 
accordance with applicable regulations including GCP, and GSKCH Standard 
Operating Procedures.
Both GSKCH and the Investigator reserve the right to temporarily suspend or 
prematurely discontinue this study at any time for reasons including, but not limited 
to, safety or ethical issues or severe non-compliance. 
If the trial is prematurely terminated or suspended for any reason, the investigator site 
should promptly inform the trial subjects and should assure appropriate therapy/ 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 64 of 70

follow-up for the subjects. Where required by the applicable regulatory requirements, 
GSKCH should inform the regulatory authority(ies). 
In addition: 
1. If the investigator terminates or suspends a trial without prior agreement of 
GSKCH, the investigator site should promptly inform the sponsor and the 
IEC, and should provide the sponsor and the IECa detailed written 
explanation of the termination or suspension.
2. If the GSKCH terminates or suspends a trial, the investigator shouldpromptly 
inform the IECand provide the IECa detailed written explanation of the 
termination or suspension. 
3. If the IECterminates or suspends its approval/favorable opinion of a trial, the 
investigator should promptly notify the GSKCH and provide GSKCH with a 
detailed written explanation of the termination or suspension.
10.6. Records Retention
Following closure of the study, the investigator must maintain all site study records 
(except for those required by local regulations to be maintained elsewhere), in a safe 
and secure location.  
The records (study/ site master file) must be maintained to allow easy and timely 
retrieval, when needed (e.g., for a GSK audit or regulatory inspection) and must be 
available for review in conjunction with assessment of the facility, supporting 
systems, and relevant site staff.
Where permitted by local laws/regulations or institutional policy, some or all of these 
records can be maintained in a format other than hard copy (e.g., microfiche, scanned, 
electronic); however, caution needs to be exercised before such action is taken. 
The investigator must ensure that all reproductions are legible and are a true and 
accurate copy of the original and meet accessibility and retrieval standards, including 
re-generating a hard copy, if required.  Furthermore, the investigator must ensure 
there is an acceptable back-up of these reproductions and that an acceptable quality 
control process exists for making these reproductions.
The investigator must assure that the subject’s anonymity willbe maintained.  On 
CRFs or other documents submitted to GSKCH, subjects should not be identified by 
their names or initials, but by an identification code. The investigator should keep a 
separate log of subjects’ codes, names and addresses.  Documents notfor submission 
to GSKCH, e.g. subjects’ written consent forms, should be maintained by the 
investigator in strict confidence.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 65 of 70

GSK will inform the investigator of the time period for retaining these records to 
comply with all applicable regulatory requirements (GSKCH recommends that 
documents be kept for 10 years). The investigator is also required to keep subject 
identification codes on file for at least 15 years after completion or discontinuation of 
the study. The minimum retention time will meet the strictest standard applicable to 
that site for the study, as dictated by any institutional requirements or local laws or 
regulations, GSK standards/procedures, and/or institutional requirements.  
No study document should be destroy
ed without a prior written agreement between 
GSKCH and the investigator. The investigator must notify GSK of any changes in the 
archival arrangements, including, but not limited to, archival at an off-site facility or 
transfer of ownership of the records in the event the investigator is no longer 
associated with the site.
10.7. Provision of Study Results to Investigators, posting of 
Information on Publicly Available Clinical Trials Registers 
and Publication
Where required by applicable regulatory requirements, an investigator signatory will 
be identified for the approval of the clinical study report.  The investigator will be 
provided reasonable access to statistical tables, figures, and relevant reports and will 
have the opportunity to review the complete study results at a GSK site or other 
mutually-agreeable location.
GSK will also provide the investigator with the full summary of the study results.  
The investigator is encouraged to share the summary results with the study subjects, 
as appropriate.
The procedures and timing for public disclosure of the results summary and for 
development of a manuscript for publication will be in accordance with GSK Policy.
A manuscript will be progressed for publication in the scientific literature if the 
results provide important scientific or medical knowledge.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 66 of 70

11. REFERENCES
Hatcher RA, Trussell J, Nelson AL, Cates W Jr, Stewart F, Kowal D, editors. 
Contraceptive Technology. 19th edition. New York: Ardent Media, 2007(b): 28
ICH Topic 6 Guideline for Good Clinical PracticeCPMP/ICH/135/95 17th July 1996
World Medical Association Declaration of Helsinki, 59th General Assembly, Seoul 
2008
Hatcher RA, Trussell J, Nelson AL, Cates W Jr, Stewart F, Kowal D, editors. 
Contraceptive Technology. 19th edition. New York: Ardent Media, 2007(b): 28
ICH Topic 6 Guideline for Good Clinical Practice CPMP/ICH/135/95 17th July 1996
World Medical Association Declaration of Helsinki, 59th General Assembly, Seoul 
2008
Berardesca E, Skin Research and Technology 1997;3(2):126-132
Fitzpatrick, TB, The validity and practicability of sun-reactive skin types I through 
VI, Arch Dermatol.1988; 124: 869-871
Griffiths CEM, Nicotinamide 4% gel for the treatment of inflammatory acne vulgaris, 
Journal of Dermatological Treatment. 1995;6(1): S8-S10
Kaymak Y, Önder M, An Investigation of Efficacy of topical niacinamide for the 
treatment of mild and moderate acne vulgaris, J Turk Acad Dermatol. 2008; 2(4)
KhodaeianiE, Fouladi RF, Amirnia M, Saeidi M, Karimi ER, Topical 4% 
nicotinamide vs. 1% clindamycin in moderate inflammatory acne vulgaris. 
International Journal of Dermatology. 2013; 52(8): 999-1004
Rogiers V, Skin Pharmacol Appl Skin Physiol 2001;14:117–128
Shalita AR, Smith JG, Parish LC, Sofman MS, Chalker DK. Topical Nicotinamide 
Compared with Clindamycin Gel in the Treatment of Inflammatory Acne Vulgaris. 
International Journal of Dermatology. 1995; 34(6):434-7
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 67 of 70

12. APPENDICES
Appendix 1 -Abbreviations and Trademarks
Abbreviations
AE 
AdverseEvent
ANCOVA
Analysis of Covariance
°C
Degrees Celsius
CD
Compact Disc
cm
2
Square Centimeters
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
EEMCO
European Group on Efficacy Measurement of Cosmetics and other 
Topical Products
g
Grams
GCP
Good Clinical Practice
GSK
GlaxoSmithKline
GSKCH
GlaxoSmithKline Consumer Healthcare
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
ITT
Intention to Treat
LSLV
Last Subject Last Visit
mg
Milligrams
PII
Personally Identifiable Information
POC
Proof of Concept
PP
Per Protocol
RH
Relative Humidity
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
µg
Micrograms
UV
Ultraviolet
Trademark Information
Trademarks not owned by the GlaxoSmithKline group of companies:
Neutrogena
Vivatinell
Simple
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 68 of 70

Appendix 2–Inclusion / Exclusion Criteria for Review at Visit 2
Inclusion Criteria
A subject will be considered still eligible for inclusion in this study only if all of the 
following criteria apply:
5. SKIN TYPE
A. Minimum of 108and maximum of 25blemishes (papules and pustules) at 
Visit 1 and a minimum of 8 blemishes (papules andpustules) at Visit 2.
Exclusion Criteria
A subject will not beconsidered stilleligible for inclusion in this study if any of the 
following criteria apply:
1. PREGNANCY
Women who are known to be pregnant or who are intending to become pregnant over 
the duration of the study.
3. CONCURRENT MEDICATION/ MEDICAL HISTORY
C. Active skin disease in the test area.
E. Moles, cysts, tattoos, scars, irritated skin, hairs, etc. at the test area that could 
influence the investigation.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 69 of 70

 
 
SIGNATURE PAGE 
 
  
 
Date 
Signed By
 
Justification 
 
 
 
Date 
Signed By
 
Justification 
 
 
 
Date 
Signed By
 
Justification 
 
 
 
Date 
Signed By
 
 
Justification 
 
 
 
Date 
Signed By
 
 
Justification 
 
 
 
Date 
Signed By
 
 
Justification 
 
 
23-May-2017 08:32:51
 
Biostatistics Approval
Approved
23-May-2017 06:51:30
Clinical Operations Approval
Rainbow Clinical Protocol.doc
23-May-2017 06:19:06
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23-May-2017 08:33:00
 
Rainbow Clinical Protocol.doc
eldo_controlled
4.0; Most-Recent; Effective; CURRENT
Auto Issue
090032d580d464b0
Page 70 of 70
PPD
PPD
PPD