A Clinical Study to Assess the Photosensitisation and Photoallergy Potential of a Cosmetic Facial Product in Healthy Subjects
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  An unpublished work subject to trade secret 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 
GlaxoSmithKline and 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
207587

 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 1 of 65

CONFIDENTIAL
SUMMARY INFORMATION



Title:
A Clinical Study to Assess the Photosensitisation and 
Photoallergy Potential of a Cosmetic Facial Productin 
Healthy Subjects
Protocol Number:
207587
Sponsor:
GlaxoSmithKline Consumer Healthcare (GSKCH)
Rua Hungria, 1240 4º andar, Jardim Europa
São Paulo/SP –Brazil, CEP 01455-000
Tel: 
Product Name:
Facial micellar cleanser
Development Phase:
N/A
Expert Advice Outside of Normal 
Working Hours:
Tel: 
Key Protocol Authors:
PRIMARY CONTACT
Clinical Research Scientist:
, MSc
GlaxoSmithKline Consumer Healthcare 
(GSKCH)
St. Georges Avenue, Weybridge, Surrey, 
KT13 0DE. UK
Tel. 
PRIMARY CONTACT
Clinical Study Manager:
GlaxoSmithKline Consumer Healthcare 
(GSKCH)
Rua Hungria, 1240 4º andar, Jardim Europa
São Paulo/SP –Brazil, CEP 01455-000
Tel: 
Biostatistician:
Other Protocol Authors:
Clinical Supplies:
Data Manager:
Medical Expert:
, MD, Ph.D
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 2 of 65
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

Principal Investigator:
Regina M. Doi, Dermatologist
Study Site Name & Address:
AZIDUS BRASIL PESQUISA 
CIENTÍFICA E DESENVOLVIMENTO 
LTDA.
Rua: General Osório, 507 -Vila Martina 
-Valinhos –SP –Brazil 
CEP: 13271-130
Study Site Telephone Number:
Study Examiner(s):
Study examiner (s)will be assigned 
according to thesite schedule (before 
First Subject First Visit) and documented 
in the site file.
Dermatologist:
Study Dermatologistwill be assigned 
according to the site schedule (before 
First Subject First Visit) and documented 
in the site file.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 3 of 65
PPD

PRINCIPAL INVESTIGATOR PROTOCOL AGREEMENT 
PAGE
I confirm agreement to conduct the study in compliance with the protocol and any 
amendments and according to the current ICH GCP guidelines.
I acknowledge that I am responsible for overall study conduct. I agree to personally 
conduct or supervise the described study.
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.
I agree to conduct this study in full conformance with the laws and regulations of the 
country in which the research is conducted.
Investigator Name:
Investigator Qualifications:
Investigator Signature:
Date of Signature/ Agreement:
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 4 of 65
PPD
PPD

Table of Content
SUMMARY INFORMATION...............................................2
PRINCIPAL INVESTIGATOR PROTOCOL AGREEMENT 
PAGE..............................................................................4
Table of Content......................................................................5
PROCESS FOR AMENDING THE PROTOCOL...............9
PROTOCOL AMENDMENT PAGE....................................10
SYNOPSIS FOR STUDY 207587...........................................15
1. INTRODUCTION...............................................................20
2. OBJECTIVE(S) AND ENDPOINT(S)...............................22
3. STUDY PLAN.....................................................................22
3.1. Study Design.......................................................................22
3.2. Subject Restrictions...........................................................24
3.3. Type and Planned Number of Subjects............................26
3.4. Study Design and Application Amount Justification.......26
4. SELECTION OF STUDY POPULATION AND 
WITHDRAWAL CRITERIA........................................30
4.1. Inclusion Criteria...............................................................30
4.2. Exclusion Criteria..............................................................31
4.3. Screening/ Baseline Failures..............................................33
4.4. Withdrawal/ Stopping Criteria.........................................34
4.5. Subject Replacement..........................................................34
4.6. Subject and Study Completion..........................................34
5. PRODUCT INFORMATION.............................................35
5.1. Study Product.....................................................................35
5.2. Application Schedule.........................................................35
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 5 of 65

5.3. Product Assignment...........................................................36
5.3.1 Randomisation....................................................................37
5.3.2 Blinding...............................................................................37
5.3.3 Code Breaks........................................................................37
5.4. Packaging and Labelling...................................................37
5.4.1. Accountability of Product.................................................38
5.4.2. Storage of Product............................................................38
6. STUDY ASSESSMENTS AND PROCEDURES..............38
6.1. Visit 1 -Screening Visit......................................................38
6.1.1 Telephone Screening..........................................................38
6.1.2. Informed Consent.............................................................39
6.1.3. Demographics....................................................................39
6.1.4 Dermatologist Assessment.................................................39
6.1.5. Medical History and Concomitant Medication...............40
6.2. Visit 2 -Baseline Visit to Visit 18......................................40
6.2.1 Application of patches........................................................40
6.2.2 Patch Assessments..............................................................41
6.3. Visit 19 -Last Subject Last Visit (LSLV).........................43
6.3.1. Study Conclusion...............................................................43
7. SAFETY ASSESSMENTS..................................................43
7.1. Definitions of an Adverse Event and Serious Adverse 
Event.................................................................................43
7.1.1. Adverse Events..................................................................43
7.1.2. Serious Adverse Events.....................................................45
7.2. Recording Adverse Events and Serious Adverse Events.46
7.3. Evaluating Adverse Events and Serious Adverse Events47
7.4. Reporting Adverse Events and Serious Adverse Events..48
7.5. Follow-up of Adverse Events and Serious Adverse Events
..........................................................................................50
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 6 of 65

7.6. Collection of Pregnancy Information................................51
7.6.1. Time Period for Collecting of Pregnancy Information...51
7.6.2. Action to be Taken if Pregnancy Occurs.........................51
8. DATA MANAGEMENT....................................................52
8.1. Source Documents/ Data....................................................52
8.2. Electronic Case Report Form............................................52
8.3. Data Handling....................................................................53
8.3.1. Data Queries......................................................................53
9. STATISTICAL CONSIDERATIONS AND DATA 
ANALYSES....................................................................54
9.1 Sample Size Determination.................................................54
9.2. General Considerations.....................................................54
9.2.1. Definition of Analysis Populations...................................54
9.2.2. Exclusion of Data from Analysis......................................54
9.2.3. Criteria for Evaluation.....................................................54
9.2.4. Handling of Dropouts and Missing Data.........................54
9.3. Statistical Methods and Analytical Plan...........................55
9.3.1. Demographic and Baseline Characteristics.....................55
9.3.2. Primary Analysis(es).........................................................55
9.3.3. Safety Analysis(es).............................................................55
10. STUDY GOVERNANCE CONSIDERATIONS.............56
10.1. Posting of Information on Publicly Available Clinical 
Trials Registers................................................................56
10.2. Regulatory and Ethical Considerations, Including the 
Informed Consent............................................................56
10.3. Quality Control (Study Monitoring)...............................56
10.4. Quality Assurance............................................................57
10.5. Conditions for Terminating the Study............................57
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 7 of 65

10.6. Records Retention............................................................58
10.7. Provision of Study Results to Investigators, posting of 
Information on Publicly Available Clinical Trials 
Registers and Publication................................................59
11. REFERENCES..................................................................60
12. APPENDICES...................................................................61
12.1. Appendix 1 -Abbreviations and Trademarks................61
12.2. Appendix 2 -Dermal Response Score.............................62
12.3. Appendix 3 -Fitzpatrick Skin Type Grading.................64
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 8 of 65

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 of 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 IRB in accordance with local requirements, before the revised edition can 
be implemented. 
All non-substantial/ minor/ administrative amendments should be submitted to the 
IRBas 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 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 9 of 65

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
Todelete 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    
Correction to errors in text to 
reflect the schedule of events
and details in main sections; 
patch sites will be assessed 48 
hours after patch removal and 
irradiations on Tuesdays in the 
Induction Phase.
Clarify wording: AND ONCE 
FOR FINAL INDUCTION 
PHASE PATCH 
GRADING/ASSESSMENT 
ON THE FIRST DAY OF 
THE REST PHASE (VISIT 
14/DAY 22) 
Clarify wording that if a 
Informed Consent   
Yes No
Safety Statement     
Yes No
CRF                       
Yes No
SYNPOSIS:
Brief Summary and 
Study Design
3.1 Study Design
Study Design
3.1 Study Design
3.1 Study Design
Signature:
Protocol 
Version 
No.:2.0
Substantial/ Major           
Date:
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68

subject develops a combined 
irritation score of 3 or greater 
during the Induction Phase, the 
site will not be irritated, a new 
patch will be applied to a naïve 
site, which will be irritated 
following removal 24 hours 
later and per the schedule of 
events.
3.4 Study Design 
and application 
Amount Justification
6.2.2 Patch 
Assessment
12.2 Appendix 2
Amendment 
No.:
Non-
Substantial/Minor    
Informed Consent   
Yes No
Safety Statement     
Yes No
CRF                       
Yes No
Signature:
Protocol 
Version 
No.:
Substantial/ Major           
Date:
Amendment 
No.:
Non-
Substantial/Minor    
Informed Consent   
Yes No
Safety Statement     
Yes No
CRF                       
Yes No
Signature:
Protocol 
Version 
No.:
Substantial/ Major           
Date:
Amendment 
No.:
Non-
Substantial/Minor    
Informed Consent   
Yes No
Safety Statement     
Yes No
CRF                       
Yes No
Signature:
Protocol 
Version 
No.:
Substantial/ Major           
Date:
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68

SCHEDULE OF EVENTS
Study Phase
Screening
Induction
Rest
Challenge
Study Week
-
Week 1
Week 2
Week 3
Week 
4-5
Week 6
                       Study Day                                   
Procedure/
Assessment
VISIT 1 
DAY -14 
to 
DAY 0
VISIT 2
DAY 1
VISIT 3 
DAY 2
VISIT 4 
DAY 4
VISIT  5 
DAY 5
VISIT 6 
DAY 8
VISIT 7 
DAY 9 
VISIT 8 
DAY 11
VISIT 9 
DAY 12
VISIT 10 
DAY 15 
VISIT 11 
DAY 16
VISIT 12 
DAY 18
VISIT 13 
DAY 19
VISIT 14 
DAY 22 
VISIT 15 
DAY 36
VISIT 16 
DAY 37
VISIT 17 
DAY 38
VISIT 18 
DAY 39
VISIT 19 
DAY 40
Day of Week
-
Mon
Tue
Thu
Fri
Mon
Tue
Thu
Fri
Mon
Tue
Thu
Fri
Mon
Mon
Tue
Wed
Thu
Fri
Informed Consent
X
Demographics
X
Medical History
X
Current/Concomitant 
medication review 
X 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Fitzpatrick Skin Type 
Assessment
X
Inclusion/Exclusion Criteria
X
Xa
Dermatologist Assessment a
X
X
X
Subject Eligibility
X
X
Continued Eligibility
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Randomisation
X
Patch Application 
Xb
Xb
Xb
Xb
Xb
Xb
X c
Patch Removal
Xd
Xd
Xd
Xd
Xd
X e
X
UVA Irradiation
X
X
X
X
X
X
X f
Grading/Assessment of the 
patch sites 
X g
X
X 
X 
X 
X
X 
X 
X 
X 
X 
X
X h
Xi
X 
X j
Xj
Xj
Adverse Eventsk
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
Study Conclusion/
Exit from Study/
X
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68

Note: Visit 1 and Visit 2 could occur on the same day but Visit 2 must be within 
14 days of Visit 1.
a. Performed by a qualified dermatologist(Inclusion criteria 3c)
b. Subjects will report to the study site 12times during the Induction Phase -6 patch 
application visits–patches will be applied Mondays and Thursdays. The patches will 
remain in place for 24hours during the week.  
c. Challenge Phase Patch application (Visit15/Day 36)-2patches will be applied to 
naïve (virgin) skin sites.The patches will remain in place on the naïve sites for 
24(±2) hours and will be evaluated at 30minutes (up to 1 hour) after patch removal 
and again at 24(±2), 48(±2) and 72(±2)hoursafter patch removal (e.g., apply the 
patcheson Monday, remove the patcheson Tuesday, and evaluate the sites on 
Wednesday, Thursday and Friday. (Challenge Phase)
d. 30 minutes (up to 1 hour) after each removal of the patches, a trained blinded assessor
will perform an assessment of all test sites for irritation symptoms using the scoring 
system detailed in Appendix 2
e. Visit 13/Day 19 will be the final Induction Phase patch removal -Approximately 30 
minutes (up to 1 hour) afterremoval of the patch, a trained blinded assessorwill 
perform an assessment of all test sites for irritation symptoms using the scoring 
system detailed in Appendix 2 
f. UVA Irradiation during the Challenge Phase will only be on one of the twothe naive 
patch locations.
g. Visit 2 (Day 1) Baseline grading/assessments of the patch sites will be performed 
prior to the patch application.
h. Final Grading/assessment of irradiation from the Induction Phase will be carried out 
on Visit 14/Day 22 (first Day of the Rest Phase).
i. Visit 15 (Day 36) Grading/assessments of each of the naïve challenge patch sites will 
be performed prior to application of the 2 Challenge patches. 
j. Further evaluations of the naïve patch sites (irradiated and non-irradiated) 24 (±2), 48 
(±2) and 72 (±2) hours after the challengepatches are removed.
k. Subjects are asked to report any adverse events from Visit 2 (or Visit 1 if patch 
application occurs at Visit 1) and the use of any concomitant medications throughout 
the study.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 13 of 65

Patch Schedule
INDUCTION
REST
CHALLENGE
Week 1
Week 2
Week 3
Week 
4-5
Week 6
Activity
MON
TUE
THU
FRI
MON
TUE
THU
FRI
MON
TUE
THU
FRI
MON
TUE
WED
THU
FRI
Application of the 1stpatch
X
Removal of the 1stpatch / 
Assess/UVAIrradiation
X
Assess 1stpatch/Applicationof
the 2
ndpatch 
X
Removal of the2ndpatch / 
Assess/UVAIrradiation
X
Assess 2ndpatch/Application of 
the 3rdpatch
X
Removal of the 3rdpatch / 
Assess/UVAIrradiation
X
Assess 3rdpatch/Application of 
the 4hpatch
X
Removal of the 4thpatch / 
Assess/UVAIrradiation
X
Assess 4thpatch/Application of 
the 5thpatch
X
Removal of the 5thpatch/
Assess/UVAIrradiation
X
Assess 5thpatch/Application of 
the 6thpatch
X
Removal of the 6thpatch/
Assess/UVAIrradiation
X
Assess Challenge Patch naïve 
sites (prior to Challenge patch 
application)
X
Application of the Challenge 
patches (2 patches)
X
Removal of the Challenge
patches/Assess/UVAIrradiation
(to onechallenge patchlocation)
X
Evaluation after Irradiation
X
X
X
Dermatologist Assessment
X
X
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 14 of 65

SYNOPSIS FOR STUDY 207587
Brief Summary
A cosmetic product that is freely available to the consumer must be safe when applied
under normal or reasonably foreseeable conditions of use. Asa general requirement, 
the safetyand compatibilityof a newformulationshouldbe confirmed before it is 
commercialised (Guidelinefor the Safety Evaluation of Cosmetic Products; Agência 
Nacional de Vigilância Sanitária, ANVISA, 2012).
Compatibility studies, performed aspatch tests, aim to confirm the local tolerance of
topicalcosmetic productsduring the first application to the skin, therefore providing 
assurancethat the product is safe for useunder maximized conditions (ANVISA, 
2012).
Phototoxicity assessments aim to demonstrate the absence of irritation potential of a 
product when applied to the skin and exposed to ultra violet (UVA) radiation. 
Photosensitisation assessments aim to prove the absence of allergic potential of a 
product applied to the skin when exposed to UVAradiation.
In this three-phase phototoxicity-photosensitisation (PT-PA) study,the test material
and a positive control of saline solution areapplied underasemi-occlusive patch to 
the upper back of each subject. The first phase of the study is an Induction Phase; a 
controlledamount of the test product and control product is applied over adefined 
surface area of skin (amountper unit area), under asemi-occlusive patch.  The patch
will remain on the skin for 24(±2) hours during this phase.  Following patch removal,
the patch site will be exposed to ultraviolet –A (UVA)radiation and re-assessed 24
48 hours later prior to re-application of another semi-occlusive patch (with both the 
test and control product) to the same site. The Induction phase will last 3 weeks. After 
a subject completes the Induction Phase they willenter a Rest Phase of 2 weeks’
duration, during which no patches will beapplied.  After the Rest Phase, subjects will 
return to the clinical site for the Challenge Phase.  In the Challengephase two test 
patches will beapplied to virgin skin areas on each subject’supper back for 24hours. 
Following removal of both patches,one of the Challenge patch test sites will be
exposed to UVAradiation. Both Challenge patch test sites will beassessed up until 
72 (±2) hours later.
The objective of this clinical study is to assess the phototoxicity and 
photosensitisationpotential of acosmetic test productunder exaggerated conditions 
of usewith controlled product application and under supervision of a dermatologist.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 15 of 65

Objective(s) and Endpoint(s)
Objective(s)
Endpoint(s)
Primary
To determine the photoirritation and 
photosensitisationpotential of a cosmetic 
facial skin productafter repeated patch 
applications to the skin of healthy 
subjects.
Trained assessorassessment of local 
tolerancethrough visual assessment of 
cutaneous irritation viathe combined 
dermal response and other effects scores 
over the induction and challenge phase.
Secondary
To evaluate the tolerance ofa cosmetic 
facial skin product.
Assessment of frequency and severity of 
Adverse Events
Study Design
Overall Design
This is an assessor-blinded (single), test site randomised, intra-subject comparison, 
repeated insult patch test to evaluate the skin irritation and sensitisation potential ofa 
cosmetic facial product,under exaggerated conditions of usewith controlled product 
application and under supervision of a dermatologist.
Day -14 to 0 / Visit 1 -Screening Visit
NOTE:Visit 1 and Visit 2 could be combined
The following assessments will be conducted:
1. Subject Informed Consent taken
2. Subject demographics collected
3. Medical history details
4. Details of current and concomitant medication collected
5. Fitzpatrick Skin Type Assessment (Appendix 3) 
6. Inclusion/Exclusion criteria 
7. Dermatologist determination for eligibility to participate in the study 
(including visual examination of the dorsum scapular region)
8. Subject eligibility
Days 1 to 22 / Visit 2 -Visit 14-Induction Phase (3 Weeks)
NOTE:Visit 1 and Visit 2 could be combined
1. The following assessments will be conducted:
2. Continued eligibility check
3. Current/Concomitant Medications review
4. Inclusion/Exclusion criteria review (Inclusion criteria 3c (only) at Visit 2, if 
Visit 1 and 2 are not combined).
5. Dermatologist determination for continued eligibility to participate in the 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 16 of 65

study (Visit 2/Day 1 only -  if visits not combined)
6. Test Site Designation and Randomisation (Visit 2/Day 1 only)
7. Baseline grading/assessment of test sites (Per Appendix 2) (Visit 2/Day 1 
only)
8. Patch applications (6 patch applications every Monday and Thursday, for 3 
consecutive weeks).
9. Patch removal 24 (± 2) hours after application (Tuesday and Friday). Reaction 
grading/assessment performed by a qualified staff member (24 ±2 hours after 
application). Grading/assessments will be 30 minutes (up to 1 hour) after each 
patch removal (per Appendix 2) 
10.Application site exposed to UVA irradiation.
11.2448(± 2) hours after each UVA irradiation (or 72 (± 2) hours, in case of 
irradiation on Fridays), the sites will be evaluated for signs of dermatological 
reactions, according to Appendix 2.
12.Adverse event assessment
NOTE: Subjects will report to the study site 12times during the Induction Phase (6 
patch applications and removals) AND ONCE FOR FINAL INDUCTION PHASE 
PATCH GRADING/ASSESSMENT ON THE FIRST DAY OF THE REST 
PHASE (VISIT 14/DAY 22).No Patch Applications from Days 22 to 35(Rest 
Phase).
Days 22-Day 35/ Visit 14 -Visit 15 –Rest Phase (2 Weeks) 
No Patch Application  
Days 36 to 39 / Visit 15-Visit 18 –Challenge Phase
The following assessments will be conducted:
1. Continued eligibility check
2. Current/Concomitant Medicationsreview
3. Grading/assessmentof naïve challenge patch sites performed by a qualified 
staff member (per Appendix 2) prior to Challenge patch application (Visit 
15/Day 36).
4. Challenge Patch application, 2 patches to naïve sites (Visit 15/Day 36).
5. Patch removal 24 (± 2) hours later (Visit 16/Day 37).
6. Reaction grading/assessment performed by a qualified staff member 30 
minutes (maximum 1 hour) after patch removal (Visit 16/Day 37).
7. One of the naïve patched sites will be exposed to 5 Joules per square 
centimeter(J/cm
2) UVA radiation.
8. Subjects will return for grading/assessment performed by a qualified staff 
member 24 (± 2) hours after UVA irradiation (Visit 17/Day 38). Both 
irradiated non non-irradiated sites will be assessed.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 17 of 65

9. Subjects will return for grading/assessment performed by a qualified staff 
member 48(± 2) hours after UVA irradiation (Visit 18/Day 39). Both 
irradiated non non-irradiated sites will be assessed.
10.Adverse event assessment.
Day 40 / Visit 19–End of Study
The following assessments will be conducted:
1. Current/Concomitant Medicationsreview
2. Adverse event assessment.
3. Subjects will return for grading/assessment performed by a qualified staff 
member 72(± 2) hours after UVA irradiation (Visit 19/Day 40). Both 
irradiated non non-irradiated sites will be assessed.
4. Dermatologist final assessment
5. Subject discharge from the study site following completion of all study 
procedures.

Type and Planned Number of Subjects

Approximately 40healthy subjects will be screened to randomise at least 30 subjects 
to ensure at least 25evaluablesubjects complete the entire study. This sample size is 
standard in clinical testing practices and is consistent with theANVISA guidelines 
(ANVISA, 2012).
Diagnosis and Main Criteria for Inclusion
Healthy male and female volunteers aged 18 to 65 with no dermatological disorders, 
with a Fitzpatrick skin phototype II toIV will be enrolled into this study. 
Product Information
Test Product 
Reference Product 
Product Name 
Facial micellar cleanser
Saline Solution: Sodium 
Chloride (NaCl; 0.9%)
Product Formulation 
Code (MFC)
N/A
Site to supply
Product Format
200ml clear PET Bottle
N/A
Application Quantity
0.02 millilitres per square 
centimetre(ml/cm
2)
0.02 ml/cm
2
Route of Administration
Topical application via semi occlusive patch
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 18 of 65
CCI

Application Instructions
Applied on-site by technician
Statistical Methods
The focus of the statistical analysis will be the evaluationof the frequency and level 
of irritation and sensitisation responsesofthe investigational product.All subjects 
with any product applied will be included in the analysis population.
Individual observations will be assessed based onAppendix 2and a narrative 
description of all skin responses, both in the induction and challenge phases,will be 
provided.  A frequency tabulation of the number of subjects with any skin response 
versus those without any skin response will be presented by
 treatment for both the 
induction and challenge phases of the study. If there are subjects with non-zero 
dermal response or superficial irritation scores, a combined dermal and others effects 
score will be determined across all time points over the induction and challenges 
phases as well as at each assessment time point and summarised using descriptive 
statistics.
No interim or subgroup analyses are planned.
Adverse Events(AE) will be tabulated according to the current version of the 
Medical Dictionary for Regulatory Activities (MedDRA). Frequencies and 
percentages will be presented overall, for each system organ class, and for each 
preferred term. Summaries of treatment-emergent AEs, treatment-related AEs, AEs 
leading to discontinuation, and serious AEs will be completed. For treatment-related 
AEs, these will also be presented by treatment /test site.
Detailed methodology for summary and statistical analyses of the data collected in 
this study will be documented in a Statistical Analysis Plan, which will be maintained 
and signed off prior to study unblinding.  
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 19 of 65

1. INTRODUCTION
In recent years the cosmetic industry has grown considerably, along with its concern
for developing safe and effective products. This industry awareness, and consumer
and regulatory agency requirements have led cosmetic manufacturers to adopt
procedures that provide them with a better understanding of their products. This 
includesthe conduct of clinical tests to assess safety and efficacy, which are often 
coordinatedby dermatologists or other experts before marketing a product. These 
proceduresprovide greater assurance of safety for the companies, increase their 
credibility, andincrease confidence among consumers.
A cosmetic product that is freely available to the consumer must be safe when applied
under normal or reasonablyforeseeable conditions of use (ANVISA, 2012). Thus, the
raw materials used in the product formulation must be of proven safety and with
established use in the cosmetic industry. As a general requirement, the safety of the
final formulation must also be confirmed before it is marketed.
Skin contact with topical products such as cosmeticsmay triggerdifferent types of 
reactions including eczematouscontact dermatitis, urticaria, acneand spots. Contact 
dermatitis can arise from two mechanisms: primary irritation,through the action of 
irritant substances; or sensitisation, in the presence of anallergenic ingredient.
Clinical studiesto evaluate the irritation and sensitisation potential of a product must 
take intoaccount a number of variables: components used in the formulation, 
ingredientconcentration, absorption, amount applied, skin condition, application 
directions andfrequency, aswell as the cumulative effect (Dooms-Goossens, 1993).
A common method to assess the potential of a topical product to cause irritation or
sensitisationinvolves repeated applications of a product to the skinunder semi-
occlusive patches(Basketter, 2008).  Thesemi-occlusion provides a higher degree of 
contact between the components of the product formula andthe skin. Therefore, it is 
considered to be asensitive method to assess the photoirritation and 
photosensitisationpotential of topically applied products.
Several types of substances do not present an inherent irritant or allergenic potential, 
however,they may provoke skin reactions when exposed to sunlight, either because 
ultraviolet radiation converts them into other substances, or because they are photo 
activated to excited states capable of interacting with the skin. (Billhimer, 1990).
Specifically, topically applied agents can cause contact dermatitis or interact with 
sunlight to cause phototoxic reactions. These reactions occur on first exposure to the 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 20 of 65

product and usually resemble exaggerated sunburnand may be characterised by a 
sensation ofprickling and burning. 
Among the several types of safety assays in humans, patch testsare currently the 
most widespread protocols conducted in order to investigate the potential risk for 
possible irritation and/or sensitization agents that, when in contact with the human 
skin, may trigger a reaction. 
Skin sensitisation is an immunological process in which the responsiveness to a 
specific chemical allergen is increased. By definition, skin sensitisation is induced 
when a susceptible individual is exposed to an inductive chemical allergen. This 
allergen causes a skin immune response that, at a certain range, will result in the
development of contact sensitisation (Kimber et al.). 
The phototoxicity test measures the potential of a test product to produce phototoxic 
reactions inhuman subjectsupon exaggerated application. Evaluator comparison of 
cutaneous responses to test product alone, test productexposed to UVAradiation and 
anirradiated, control productsite provides an assessment of the phototoxic potential 
of the test product.  
Topically applied products may contain one or more ingredients that can be converted 
to a photoantigen by UVA radiation. In certain individuals,the photoantigen can then 
trigger an inflammatory response by the immune system and produce an allergic 
reaction upon subsequent exposure to the product in sunlight. 
The photoallergenicity test measures the potential of test products to produce allergic 
reactions in the presence of UVA radiation. This test consists of three phases: a 3-
week Induction phase consisting of repeated 24 hour semi-occlusive patch 
applications on the backs of healthy subject and subsequent exposure to UVA 
radiation after each patch removal; a2 week Restphase; and a final Challenge phase, 
consisting of two parallel 24 hour semi-occlusive patch applications to naive sites, 
one of which is subsequently exposed to UVA radiation upon patch removal, and 
evaluation of cutaneous responses of both sites 24, 48 and 72 hours after patch 
removal.
The inclusion of evaluations at 24, 48 and 72 hours forthe two challenge sites (with 
and without exposure to UVAradiation) providessimultaneous evaluation of the 
potential for contact irritation, phototoxicity, contact allergy and photoallergy.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 21 of 65

The objective of this clinical study is to assess the phototoxicity and 
photosensitisationpotential of acosmetic test productunder exaggerated conditions 
of usewith controlled product application and under supervision of a dermatologist.
2. OBJECTIVE(S) AND ENDPOINT(S)
Objective(s)
Endpoint(s)
Primary
To determine the photoirritation and 
photosensitisationpotential of a cosmetic 
facial skin product after repeated patch 
applications to the skin of healthy 
subjects.
Trained assessor assessment of local 
tolerance through visual assessment of 
cutaneous irritation via the combined 
dermal response and other effects scores 
over the induction and challenge phase.
Secondary
To evaluate the tolerance of a cosmetic 
facial skin product.
Assessment of frequency and severity of 
Adverse Events
3. STUDY PLAN
3.1. Study Design
Overall Design
This is an assessor-blinded (single), test site randomised, intra-subject comparison, 
repeated insult patch test to evaluate the skin irritation and sensitisation potential ofa 
cosmetic facial product,under exaggerated conditions of usewith controlled product 
application and under supervision of a dermatologist.
Day -14 to 0 / Visit 1 -Screening Visit
NOTE:Visit 1 and Visit 2 could be combined
The following assessments will be conducted:
1. Subject Informed Consent taken
2. Subject demographics collected
3. Medical history details
4. Details of current and concomitant medication collected
5. Fitzpatrick Skin Type Assessment (Appendix 3) 
6. Inclusion/Exclusion criteria 
7. Dermatologist determination for eligibility to participate in the study 
(including visual examination of the dorsum scapular region)
8. Subject eligibility
Days 1 to 22 / Visit 2 -Visit 14-Induction Phase (3 Weeks)
NOTE:Visit 1 and Visit 2 could be combined
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 22 of 65

1. The following assessments will be conducted:
2. Continued eligibility check
3. Current/Concomitant Medications review
4. Inclusion/Exclusion criteria review (Inclusion criteria 3c (only) at Visit 2, if 
Visit 1 and 2 are not combined).
5. Dermatologist determination for continued eligibility to participate in the 
study (Visit 2/Day 1 only -  if visits not combined)
6. Test Site Designation and Randomisation (Visit 2/Day 1 only)
7. Baseline grading/assessment of test sites (Per Appendix 2) (Visit 2/Day 1 
only)
8. Patch applications (6 patch applications every Monday and Thursday, for 3 
consecutive weeks).
9. Patch removal 24 (± 2) hours after application (Tuesday and Friday). Reaction 
grading/assessment performed by a qualified staff member (24 ±2 hours after 
application). Grading/assessments will be 30 minutes (up to 1 hour) after each 
patch removal (per Appendix 2) 
10.Application site exposed to UVA irradiation.
11.2448(± 2) hours after each UVA irradiation (or 72 (± 2) hours, in case of 
irradiation on Fridays), the sites will be evaluated for signs of dermatological 
reactions, accordingto Appendix 2.
12.Adverse event assessment
NOTE: Subjects will report to the study site 12times during the Induction Phase (6 
patch applications and removals)ANDONCE FOR FINAL INDUCTION PHASE 
PATCH GRADING/ASSESSMENT ON THE FIRST DAY OF THE REST 
PHASE (VISIT 14/DAY 22)No Patch Applications from Days 22 to 35 (Rest Phase).
Days 22-Day 35/ Visit 14 -Visit 15–Rest Phase (2 Weeks) 
No Patch Application  
Days 36 to 39 / Visit 15-Visit 18 –Challenge Phase
The following assessments will be conducted:
1. Continued eligibility check
2. Current/Concomitant Medicationsreview
3. Grading/assessmentof naïve challenge patch sites performed by a qualified 
staff member (per Appendix 2) prior to Challenge patch application (Visit 
15/Day 36).
4. Challenge Patch application,2 patches to naïve sites (Visit 15/Day 36).
5. Patch removal 24 (± 2) hours later (Visit 16/Day 37).
6. Reaction grading/assessment performed by a qualified staff member 30 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 23 of 65

minutes (maximum 1 hour) after patch removal (Visit 16/Day 37).
7. One of the naïve patchedsites will be exposed to 5 Joules per square 
centimeter (J/cm
2) UVA radiation.
8. Subjects will return for grading/assessment performed by a qualified staff 
member 24 (± 2) hours after UVA irradiation (Visit 17/Day 38). Both 
irradiated non non-irradiated sites will be assessed.
9. Subjects will return for grading/assessment performed by a qualified staff 
member 48(± 2) hours after UVA irradiation (Visit 18/Day 39). Both 
irradiated non non-irradiated sites will be assessed.
10.Adverse event assessment.
Day 40 / Visit 19–End of Study
The following assessments will be conducted:
1. Current/Concomitant Medicationsreview
2. Adverse event assessment.
3. Subjects will return for grading/assessment performed by a qualified staff 
member 72(± 2) hours after UVA irradiation (Visit 19/Day 40). Both 
irradiated non non-irradiated sites will be assessed.
4. Dermatologist final assessment
5. Subject discharge from the study site following completion of all study 
procedures.

3.2. Subject Restrictions
Lifestyle/ Dietary
During the entire study (Screening –Last Subject Last Visit (LSLV)) the following 
should be avoided:
1. Applying any other product, including cosmetics,moisturisers and other 
topical products to the test site (dorsum).
2. Changingany cosmetic habits, including personal hygiene.
3. Changingdietaryhabits.
4. Getting the patches wet: during showers or bathing, in pools or lakes/ocean, 
sauna or activities that cause excessive sweating. The study site will provide 
instructions on how to shower or bathe throughout the study.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 24 of 65

5. Removingthe patches.
6. Wearingtight or restrictive clothingthat can remove the patch through friction 
or cause redness.
7. Exposureof the back tosunlight, artificial UV light or cosmetic procedures 
(includes tanning beds, Intense Pulsed Light, etc.).
8. Introduction of new personal care/household products including but not 
limited to; soap, laundry detergent, or fabric softener.
9. Engaging in activities that are expected to result in excessive sweating. 
10.Missing the first day of application during the Induction Phase, or the day of 
application during the Challenge Phase.
11.Missing 2 or more consecutive visits or more than 2 alternative visits.
Medications and Treatments
During the entire study (Screening –LSLV) the following medications and treatments 
should be avoided:
1. Having anyaesthetic or dermatological treatment performedon the body.
2. Changinghormone treatment.
3. Changingcontraceptive method.
4. Not tonot use the following medications:
a. Systemic or topicalcorticosteroids
b. Systemic or topical immunosuppressive drugs
c. Systemic or topical antihistamines, Vitamin A acid and its derivatives, 
or non-steroidal anti-inflammatory drugs 
d. Concomitant topical treatment at test sites
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 25 of 65

3.3. Type and Planned Number of Subjects
Approximately 40healthy subjects will be screened to randomise at least 30 subjects 
to ensure at least 25evaluablesubjects complete the entire study. This sample size is 
standard in clinical testing practices and is consistent with theANVISA guidelines 
(ANVISA, 2012).
Healthy male and female subjectsaged 18 to 65 with no dermatological disorders and 
with a Fitzpatrick skin phototype II toIV will be enrolled into this study. 
3.4. Study Design and Application AmountJustification
Study Design:
This will be a single-center, randomised, assessor(single) blind study in healthy 
subjects aged 18 to 65years. Subjects will be exposed to repeated insult dermal semi-
occlusive patch application of atopical cosmetic formulationand negative control
(saline solution).
Screening:
During screening subjects will sign an informed consent document and then a 
dermatological assessment will be conducted to ensure subjects have no 
dermatological conditions ontheir dorsum (backs) that might impact subject safety or 
study results and to ensure subjects haveFitzpatrick Phototype IIto IV.
Each subject’s medical history and medication history will be reviewed, as well as 
inclusion/exclusion criteria. After which, site staff will review lifestyle guidelinesand 
directions with eligible subjects.
Induction Phase:
Visit 2/Day 1 of the Induction phase could be combined with Visit 1.
On Day 1 ofthe Induction Phase, eligible subjects will return to the study site and 
another dermatological assessment will be conducted to ensure continued eligibility 
(if Visits 1 and 2 are not combined) as well as review of concomitant medications 
since screening. The test sitewill be designated above the waist between the left 
scapula and the spinal mid-line. The sites within the patch of test product and 
negative control application will be randomly assigned and baseline 
grading/assessment of each test site will be performed.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 26 of 65

During the induction phase, there will be 6patch applications(a patch will contain 
both the test product and saline solution)over 3 consecutive weeks, with each patch
applied on Mondays and Thursdays. Each patchwillremain in place for 24 (± 2) 
hours and then be removed, the treated areas willbe cleaned with saline solution.  
After 30 minutes (maximum of 1 hour) the sites will be graded/evaluated as per the 
scale in Appendix 2. The patch test site will then be exposed to5 J/cm
2UVA 
radiation. The patch application sitewill be assessed pre-irradiation, following patch 
removal. Irradiation time depends on the power output of the light source and 
distance from the subject, and will be determined by
 the study site prior to UVA 
exposure.  Irradiation will occur on the same days as patch removal (Tuesday and 
Fridays). Assessment of the irradiated sites will occur 48 hours (or 72 hours if the 
irradiationoccurred on a Friday) after UVA exposure, prior to new patch application 
to the same site.
Rest Phase:
Afterthe last grading/evaluation of the Induction Phase, subjects will enter a Rest 
Phase of 2 weeks.  During this time there will be no product patchapplications.
Challenge Phase:
After completing the Rest Phase, subjects will return for the Challenge Phase. Two 
naïve sites (previously un-patched, virginareas) will be selected for the challenge 
patches both ofthese naïve areas will be graded/evaluated prior to any product 
application. Twopatches, each withthe test product and saline solution, will be 
randomly applied to each of the Challenge sites for 24(± 2) hours, according to each 
subject’s random assignment on Day 1 of the Induction phase.  After 24 (± 2) hours, 
subjects will return for Challenge patch removal,the sites willbe cleaned with saline 
solutionand then graded/evaluated after 30 minutes (maximum of 1 hour).  Oneof 
the Challenge patch sites will then be irradiated with 5 J/cm
2of UVA radiation. 
Subjects will return 24 (± 2), 48 (± 2), and 72 (± 2) hours after patch removal for 
further grading/assessmentsof both the irradiated and non-irradiated Challenge sites. 
End of Study:
After the Challenge phase is complete, a final clinical assessment by a qualified 
dermatologist will be performed to ensure that it is medically appropriate to exit each 
subject from the study. After all study assessments are completed, subjects will be 
discharged from the study site. 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 27 of 65

Adverse events and concomitant medications will be assessed throughout the study. 
Patch Assessments:  
The results of the patch site assessments (Appendix 2) will be presented as individual 
responses to each test product and the negative control (saline solution) at each 
assessment time point. All responses will be reviewed in context of the grading scale.
Assessment of the patch sitewill be conducted once at Baseline (Visit 2/Day 1) prior 
to any patch applicationand then a further 11times post-baseline during the 
Induction Phase, once during the Rest Phase (for the final assessment of irradiated 
patch site), and5times during the Challenge Phase by a blinded assessor (a qualified 
staff member).  Sites will be assessed prior to UVA exposure to allow responses to 
minimize the impact of UVA-induced erythema or pigmentation.
Any skin response at a patched site will be clinically assessed using the criteria 
recommended by the US Department of Health and Human Services Food and Drug 
Administration (FDA), 1999.
Each of the scores represents an effect that is localised in a representative portion of 
the patch area, defined as 25% or more of the patch test site. Individual observations 
will be recorded in tables and a narrative description of all skin responses (any 
score>0) will be provided. Superficial irritation scores are only provided if there is a 
dermal response score >0.
Each Superficial Irritation Score should be reported as a letter. The combined score 
will equal the sum of the dermal response score plus the numerical equivalent of the 
superficial irritation score (e.g.  dermal response score=3 and superficial irritation 
score=”C” implies a combined score of 3 + 2 = 5).
If a subject develops a combined score of 3 or greaterat any pointduring the 
Induction phase, IRRADATION OF THE SITE WILL NOT BE PERFORMED, 
the patch will be applied to an adjacent naïve site for the next application. If a 
combined score of 3 or greater occurs at the naïve site, no further patch applications 
will be made. Such reactive subjects will, however, receive patches on naïve test sites 
during the challenge phase of the study unless, in the opinion of the Investigator, it 
would be unwise to do so.  
Dermal irritation or sensitisation reactionswithinthe patch area (i.e., irritation 
reactions outlined in Appendix 2) will not be recorded as AEs during the study. 
Reactions to the patch itself will also not be recorded as AEs.Unexpected reactions 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 28 of 65

(e.g., rash, hives) will be recorded as AEs. As each subject will beexposed to UVA 
radiationduring the induction and challenge phases, it isexpected that the sites 
become hyperpigmented and may exhibit erythema as a natural response to UVA 
exposure. These responses are expected and will be disregarded in evaluations, using 
the negative control (salinesolution) as the standard for determining the expected 
degree of reaction.
Reactions observed after application of patches and before UVA exposure, or 
observed on the non-irradiated site during the challenge phase, will be used to 
evaluate the primary irritation potential of the product. These data will not be used to 
evaluate the photoirritation or photosensitisationpotential of the formulation.
Application Amount Justification:
The prerequisite for a patch test is the requirement that the whole test site is covered 
with the test product, without spreading or overlapping into other test sites. Previous 
work (Isaksson, 2007) has shown that the optimal dose to fulfil these requirements is 
0.02 ml/cm
2.
The test product will be distributed over the patch test filter paper discs (semi 
occlusive patch application) in the amount of 0.02 ml, and applied to designated sites 
on the back. A sodium chloride (NaCl) saline solution (0.9%) will be used as the 
negative control and will also be applied to the back through semi-occlusive 
application.
The semi-occlusive patches are made of a hypoallergenic material with round 
chambers (or cells) of an absorbent material. Standardized amounts will be applied in 
these cells, approximately 0.02 ml (if application with a pipette is possible) or 20 mg 
(if application with a pipette is not possible, in this study, only products of the 
sponsor, GlaxoSmithKline will be testedwith the saline solution control. One of the 
patch cells will contain the control andtherefore, will be filled in with saline solution, 
and one of the other cells will be filled with the test product.
The study will be conducted under the supervision of a qualified dermatologist.  
Prospective subjects will be assessed by the qualified staff member as a prerequisite 
to enrollment, and again at study end.
Photoreactions to exogenous agents typically occur in response to UVA light (315-
400 nanometers (nm)) rather than at the shorter wavelengths of UVB or UVC. The 
photoreactions can be divided into two types of responses; photoirritancy 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 29 of 65

(phototoxicity) and photoallergy (Norbert, 2005). A 5 J/cm
2dose of UVAradiation 
has been established as a sufficient for eliciting photo contact allergic test reactions 
(Hasan, 1996).
UVALamp:
Subject UVAirradiation will be performed with Newport 67005, serial 120 power 
supply model 69907 with filter adapter and xenon lamp of 150 Watts.
The solar simulator will be used to irradiate the test areas with the requested 
irradiation intensity on circular spots of approximately 1 cm². 
Before UVAexposure of each test site, the UVAirradiance will be measured with a 
radiometer calibrated against a spectroradiometric measurement of the solar simulator 
output.A spectroradiometric measurement of the UV source of the solar simulator is 
performed at least every 18 months by an authorized expert.
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 orother 
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 
potentially jeopardize 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. 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 30 of 65

2. AGE
Aged between 18 and 65 years inclusive.
3. GENERAL HEALTH
a.)Good general and mental health with, in the opinion of the investigator or 
medically qualified designee no clinically significant andrelevant 
abnormalities in medical history or upon physical examination.
b.)Healthy, intact skin at the proposed application site; dorsum (scapular region).
c.)Clinical assessment for eligibility (at Visit 1 and Visit 2-if not combined) by 
a dermatologist to ensure subject is free of clinically relevant dermatological 
conditions.
4. SKIN TYPE
Fitzpatrick phototype II to IV (see Appendix 3).
5. COMPLIANCE
Agreement to comply with the procedures and requirements of the study andto attend 
the scheduled assessmentvisits.
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) Any history of significant dermatological diseases or conditions or medical 
conditions known to alter skin appearance or physiologic response (e.g. 
diabetes,) which could, in the opinion of the Investigator, preclude topical 
application of the investigational products and/or interfere with the evaluation 
of the test site reaction. 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 31 of 65

b) Presence of open sores, pimples, or cysts at the application site. 
c) Active dermatosis (local or disseminated) that might interfere with the results 
of the study.
d) Considered immune compromised. 
e) History of diseases aggravated or triggered by
 ultraviolet radiation.
f) Participants with dermatographism.
g) Currently using any medication which in the opinion of the investigator, may 
affect the evaluation of the study product, or place the subject at undue risk.
h) Use of the following topical or systemic medications: immunosuppressants, 
antihistamines, non-hormonal anti-inflammatory drugs, and corticosteroids up 
to 2 weeks before screening visit.
i) Oral or topical treatment with vitamin A acid and/or its derivatives up to 1 
month before the screening visit.
j) Intention of being vaccinated during the study period or has been vaccinated 
within 3 weeks of the screening visit.
k) Currently receiving allergy injections, or received an allergy injection within 7 
days prior to Visit 1, or expects to begin injections during study participation
4. ALLERGY/ INTOLERANCE
a) Previous history of atopy, allergic reactions, irritation or intense discomfort 
feelings to topical-use products, cosmetics or medication.
b) Study subjectswith a history of allergy to the study material/product, 
hypoallergenic tape, or to the cotton patches.
c) History of sensitisation in a previous patch study.
d) History of abnormal reaction to sun exposure.
5. CLINICAL STUDY/ EXPERIMENTAL PRODUCT
a) Participation in another clinical study (including cosmetic studies) or receipt 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 32 of 65

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. DIAGNOSTIC ASSESSMENTS AND OTHER CRITERIA
a) Intense sunlight exposure or sun tanning sessions up to 30days before the 
Screening evaluation.
b) Intention of bathing(in the sea or pool), sauna, water sports,or activitiesthat 
leadto intense sweating.
c) Any Subject who, in the judgment of the Investigator, should not participate in 
the study.
d) Any skin marks on the test site that might interfere with the evaluation of 
possible skin reactions (e.g. pigmentation disorders, vascular malformations, 
scars, tattoos, excessive hair, numerous freckles).
e) Prisoner or involuntary incarcerated subject.
f) Subject from an indigenous tribe.
4.3. Screening/ Baseline Failures
Screen failures are defined as subjects who consent to participate in the study but are 
never subsequently randomized.  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 
Events. Re-screening of subjects considered previous screen failures will notbe 
allowed in this study.
8. PERSONNEL
An employee of the sponsor or the study site or members of their immediate family.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 33 of 65

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 AE or an abnormal 
laboratory test result, the principal specific event or test will be recorded on the 
electronic case report form (CRF). 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 study post-randomisation will notbe replaced.
4.6. Subject and Study Completion
A completed subject is one who has completed all phases of the study including the 
follow-up visit.
The end of the study is defined as the date of the last subject’s last visit.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 34 of 65

5. PRODUCT INFORMATION
5.1. Study Product
The following study productwill be supplied by the Clinical Supplies Department, 
GSKCH:
Test Product 
Reference Product 
Product Name 
Facial micellar cleanser
Saline Solution: Sodium 
Chloride (NaCl; 0.9%)
Product Formulation 
Code (MFC)
N/A
Site to supply
Product Format
200ml clear PET Bottle
N/A
Application Quantity
0.02 ml/cm
2
0.02 ml/cm
2
Route of Administration
Topical application via semi occlusive patch
Application Instructions
Applied on-site by technician
5.2. ApplicationSchedule
Induction Phase:
Visit 2/Day 1 of the induction phase could be combined with Visit 1.
On Day 1 ofthe Induction Phase, eligible subjects will return to the study site and 
another dermatological assessment will be conducted to ensure continued eligibility 
(if Visits 1 and 2 are not combined) as well as review of concomitant medications 
since screening. The test sitewill be designated above the waist between the left 
scapula and the spinal mid-line. The siteswithin the patch of test product and 
negative control application will be randomly assigned and baseline 
grading/assessment of each site will be performed.
During the induction phase, there will be 6patch applicationsofboth the test product 
and saline solutionover 3 consecutive weeks, each patch will beapplied on Mondays 
and Thursdays. Each patchwillremain in place for 24 (± 2) hours and then removed
and the treated areas may be cleaned with saline solution.  After 30 minutes 
(maximum of 1 hour) sites will be graded/evaluated as per the scale in Appendix 2. 
The patch test site will then be exposed to5 J/cm
2UVA radiation. The patch 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 35 of 65
CCI

application sitewill be assessed pre-irradiation, following patch removal. Irradiation 
time depends on the power output of the light source and distance from the subject, 
and will be determined by the study site prior to UVA exposure.  Irradiation will 
occur on the same days as patch removal (Tuesday and Fridays). Assessment of the 
irradiated sites will occur 48 hours (or 72 hours if the irradiation occurred on a 
Friday) after UVA exposure, prior to new patch application to the same site.
Rest Phase:
Afterthe last grading/evaluation of the Induction Phase, subjects will enter a Rest 
Phase of 2 weeks.  During this time there will be no product patch applications.
Challenge Phase:
After completing the Rest Phase, subjects will return for the Challenge Phase. Two 
naïve sites (previously un-patched areas) will be selected for the challenge patches, 
these areas will be graded/evaluated prior to any product application. Two patches, 
each withboth the test product and saline solution, will be randomly applied to each 
of the challenge sites for 24(± 2) hours, according to each subject’s random 
assignment on Day 1 of the Induction phase.  After 24 (± 2) hours, subjects will 
return for Challenge patch removal, the sites willbe cleaned with saline solutionand
then graded/evaluated after 30 minutes (maximum of 1 hour).  Oneof the Challenge
siteswill then be irradiated with 5 J/cm
2of UVA radiation. Subjects will return 24 (± 
2), 48 (± 2), and 72 (± 2) hours after patch removal for further grading/assessments of 
both the irradiated and non-irradiated Challenge patch sites.
End of Study:
After the Challenge phase is complete, a final clinical assessment by a qualified 
dermatologist will be performed to ensure that it is medically appropriate to exit each 
subject from the study. After all study assessments are completed, subjects will be 
discharged from the study site.  
5.3. Product Assignment
Each subject will have the test and reference product (saline solution) applied to their 
backs (dorsum region). The location of each product application will be assigned to 
study product in accordance with the randomisationschedule generated by the 
Biostatistics Department, GSKCH, prior to the start of the study, using validated 
internal software.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 36 of 65

5.3.1Randomisation
A unique screening number will identifyeach 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. The randomisation number will be associated with the random 
location assignment of product to test site.
5.3.2Blinding
The study statistician and other employees of the Sponsor who may influence study 
outcomes are blinded to the product allocation/test site location. Investigators 
dispensing the product will be aware of each product’s location and must not divulge 
information to the study staff or assessors. The assessor performing the assessment of 
irritation will be blinded to the product allocation.
5.3.3Code 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 
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.
5.4. 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 facial micellar cleanser (
) will be supplied in 200 mlbottles andwill 
have a study label affixed by the Sponsor.Each study label will contain, but not be 
limited to, protocol number, product codeletter and directions for storage.
The investigator or designee will supply the salinesolution (Reference Product) with 
a study label affixed. Each study label will contain the information according to the 
site specific internal requirements.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 37 of 65
CCI

Care should be taken with the supplied productand 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. 
5.4.1. Accountability of Product
The test product suppliedisfor use only in this clinical study and should not be used 
for any other purpose.
The investigator or designee will maintain a full record of study product 
accountability. A Product Dispensing Log must be kept current.
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.
5.4.2. Storageof Product
Study product supplies must be stored in compliance with the label requirements in a 
secure place with limited or controlled access.
6. STUDY ASSESSMENTS AND PROCEDURES
This section lists the procedures and parametersof 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 -Screening Visit
6.1.1 Telephone Screening
Prior to the screening visit, telephone screening of interested subjects maybe 
conducted using a telephone script. This will be conducted by the site recruitment 
staff or designee.  
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 38 of 65

6.1.2. Informed Consent
The investigator, or designee, must obtain 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.
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 signed and datedconsent 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 after 
the subject has signed.  The subject will be provided with a copy of their signed and 
dated consent form and any other written information which they are 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 copy of 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 CRF.
After signing the Informed Consent Form (ICF), subjects will undergo all the 
screening assessments to confirm that they meet all the inclusion criteria and none of 
the exclusion criteria. If the subject is considered eligible by the Investigator (or 
designee) to participate they are considered enrolled in the study.
6.1.3. Demographics
The following demographic parameters will be captured by the Investigator or 
designee and recorded on the CRF: year of birth, Fitzpatrick skin type(skin phototype 
classification, according to the Fitzpatrick classification, per Appendix 3), gender and 
race.
6.1.4 Dermatologist Assessment
For products with specific safety appeals, thestudy must be followed up by a 
specialist (ANVISA, 2012). A qualified dermatologist will assess the overall subject 
eligibility at the Screening Visit and continued eligibility in the study at Visit 2 (if not 
combined) to ensure that the subject is free of any pre-existing dermatological 
pathology. Additionally,a final assessment at Visit19by a qualifieddermatologist 
will confirmwhether it is medically appropriate to exit the subject from the study 
(Edward & Robillard, 2008).
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 39 of 65

6.1.5. Medical History and Concomitant Medication
Medical history will be assessed as related to the inclusion/exclusion criteria by the 
Investigator or medically qualified designee.  Details of any relevant medical or 
surgical history (within the last year), including allergies or drug sensitivity, will be 
recorded on the CRF.  Any concomitant therapy taken in the 30 days prior to the 
Screening Visit and throughout the study will also be recorded.
6.2. Visit 2 -Baseline VisittoVisit 18
Visit 2 may be combined with Visit 1 (Screening) but should be no more than 14 days 
following Visit 1. 
At Visit 2 any current and concomitant therapy takenwill be reviewed, and continued 
eligibility will be checked before any patch application (and randomisation of product 
application ordering). This will be reviewed again before each subsequent visit.
A qualified dermatologist will check for subject continued eligibilityin the study (At 
Visit 2 only if visits are not combined).
6.2.1Application of patches 
The test productand saline solution(0.02 ml/cm
2of each product) will be applied to a 
paper disc (or cell) contained within an adhesivepatch. The number of cells available 
on the patch test tape can vary but in this study one will be used for test product and 
one for the reference; saline solution). The patch is then applied onto the dorsum 
(scapula region) of each subjectfor a period of 24 ± 2 hours, the sequence of the 
product applicationto the cells will be according tothe randomisation schedule.
Induction Phase:
Visit 2/Day 1 of the induction phase could be combined with Visit 1.
On Day 1 ofthe Induction Phase, eligible subjects will return to the study site and 
another dermatological assessment will be conducted to ensure continued eligibility 
(if Visits 1 and 2 are not combined) as well as review of concomitant medications 
since screening. The test sitewill be designated above the waist between the left 
scapula and the spinal mid-line. The sites of test product and negative control 
application will be randomly assigned and baseline grading/assessment of each test 
site will be performed.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 40 of 65

During the Induction phase,there will be 6patch applicationsofboth the test product 
and saline solutionover 3 consecutive weeks, with each patchapplied on Mondays 
and Thursdays. Eachpatch willremain in place for 24 (± 2) hours, then removedand 
the treated areas willbe cleaned with saline solution.  After 30 minutes (maximum of 
1 hour) the sitewill be graded/evaluated as per the scale in Appendix 2. The patch 
test site will then be exposed to5 J/cm
2UVA radiation. The patch application site
will be assessed pre-irradiation, following patch removal. Irradiation time depends on 
the power output of the light source and distance from the subject, and will be 
determined by the study site prior to UVA exposure.  Irradiation will occur on the 
same days as patch removal (Tuesday and Fridays). Assessment of the irradiated sites 
will occur 48 hours (or 72 hours if the irradiation occurred on a Friday) after UVA 
exposure, prior to new patch application to the same site.
Rest Phase:
Afterthe last grading/evaluation of the Induction Phase, subjects will enter a Rest 
Phase of 2 weeks.  During this time there will be no product patch applications.
Challenge Phase:
After completing the Rest Phase, subjects will return for the Challenge Phase. Two 
naïve sites (previously un-patched areas) will be selected for the Challenge patches, 
these areas will be graded/evaluated prior to any product application. Two patches, 
each withboth the test product and saline solution, will be randomly applied to each 
of thenaïve challenge sites for 24(± 2) hours, according to each subject’s random 
assignment on Day 1 of the Induction phase.  After 24 (± 2) hours, subjects will 
return for Challenge patch removal, sites willbe cleaned with saline solutionand then 
graded/evaluated after 30 minutes (maximum of1 hour).  Oneof the Challenge patch
siteswill then be irradiated with 5 J/cm
2of UVA radiation. Subjects will return 24 (± 
2), 48 (± 2), and 72 (± 2) hours after patch removal for further grading/assessments of 
both the irradiated and non-irradiated Challenge sites.
6.2.2Patch Assessments 
An experienced trained assessor(s)will assess all the patch sites for the duration of 
the studyaccording to the scoring scale in Appendix 2. Each patch will be removed
and the treated areas willbe cleaned with saline solutionbefore visual assessment.  
Where ever possible,the same experienced trained assessor will perform all skin
assessments for a given subject at each time point.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 41 of 65

A Baseline patch site assessment will be carried out at Visit 2 (or Visit 1 if visits 
combined) prior to any patch application. Patch assessments will then be performed at 
Visits 3 to 13 for the Induction Phase (every 24± 2hours following application, and 
48 ± 2(OR 72 ± 2IN CASE OFIRRIDATION ON FRIDAYS)hoursfollowing 
patch site exposure to 5 J/cm
2UVA radiation). Afterthe last grading/evaluation in the 
Induction Phase at Visit 14, subjects will enter a Rest Phase of 2 weeks.
After completing the Rest Phase, subjects will return for the Challenge Phase (Visit 
15).  Each the naïve patch sites will be assessed prior to Challenge patch application.
The 2 Challenge patches (with both the test and saline solution products) will be 
randomly applied to the Challenge site (previously untreated areas of skin)for 24± 2
hours.  After Challenge patch removal at the study site (Visit 16), the patch site will
be cleaned with saline solutionandgraded/evaluated after 30 minutes (maximum of 1 
hour).  One of challenge patch test site will then be exposed to 5 J/cm
2UVA 
radiation. Subjects will return for further assessments after 24 ± 2hours(Visit 17), 48 
± 2hours(Visit 18) and 72 ± 2hours (Visit 19) post patch removalfor further 
grading/assessment of both the irradiated and non-irradiated Challenge sites.
Patch sites will be graded usinga magnifying glass with a fluorescent daylight lamp.
The assessor will beblinded to the treatment allocation.
The results will be presented as individual responses to each product at each 
assessment time point.
In any case of a positive reactionadermatologist will be available to perform 
secondary assessments and gradethe response with any further action as needed. This 
should occur the same day as the initial assessment performed by the trained assessor.
The intensity of any visual signs of irritation will be recorded by the trained 
examiner, according to the quantity and grade of the reactions (Appendix 2) 
according to the skin appearance (Table 1) and other features indicative of irritation 
(Table 2) observed. The trained assessoris responsible for grading the reactions, and 
the trained examiner’s opinion on the interpretation of the results is final.
If a subject develops a combined score of 3 or greaterat any pointduring the 
Induction phase,IRRADATION OF THE SITE WILL NOT BE PERFORMED
thepatch willbe applied to an adjacent naïve site for the next application. If a 
combined score of 3 or greater occurs at the naïve site, no further patch applications 
will be made. Such reactive subjects will, however, receive patches on naïve test sites 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 42 of 65

during the challenge phase of the study unless, in the opinion of the Investigator, it 
would be unwise to do so.  
Any observed response which can be denoted using the irritation criteria summarized 
in Appendix 2, will not be considered an adverse event. In addition,any tape-related 
irritation will also not be noted as an AE. Only in case of unusual reactions, these 
reactions and the consequences upon the evaluation of the respective test areas will be 
documented as AE’s.
All responses will be reviewed in context of the grading scale in this protocol 
(Appendix 2).
6.3. Visit 19 -Last Subject Last Visit (LSLV)
At Visit 19 any current and concomitant therapy takenwill be reviewed, and 
continued eligibility will be checked. Final challenge site assessment 72 ± 2hours 
(Visit 19) post patch removal (per Section 6.2.2) will take place.
A final evaluation by a qualified dermatologist will take placebefore the subject 
completes the study(per Section 6.1.4).
6.3.1. Study Conclusion
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 CRF by selecting one of the options below.
1.
Subject did not meet study criteria
2.
Adverse Event
3.
Lost to Follow Up
4.
Protocol Violation
5.
Withdrawal of Consent
6.
Other
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.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 43 of 65

Adverse Event Definition:
An AE is any untoward medical occurrence in a patient or 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.
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 
eitheran 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 
thatleads to the procedure is an AE.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 44 of 65

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.
6. Any observed response which can be denoted using the irritation criteria 
summarized in Appendix 2, will not be considered an adverse event. In 
addition,any tape-related irritation will also not be noted as an AE. Onlyin 
case of unusual reactions, these reactions and the consequences upon the 
evaluation of the respective test areas will be documented as AE’s.
7. As each subject will be irradiated during the induction phase, it isexpected 
that the sites become hyperpigmented and may exhibit erythema as a natural 
response to UVA exposure. Only in case of unusual reactions will these be 
documented as AE’s.
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 term disability means a substantial disruption of a person’s ability 
to conduct normal life functions.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 45 of 65

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
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 
surgical intervention to prevent one of the other outcomes listed in the above 
definition. These should also be considered serious.
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. RecordingAdverse Eventsand 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 the start of the product application and until 5 days 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 46 of 65

following last administration ofthe 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 consentSto 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 Eventsand 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
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:
The investigator is obligated to assess the relationship between study product and the 
occurrence of each AE/SAE.
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.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 47 of 65

The investigator willuse clinical judgment to determine the relationship.
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.
The investigator will also consult the Safety Statement and/or Product Information, 
for marketed products, in the determination of his/her assessment.
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.
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.
The investigator may change his/her opinion of causality in light of follow-up 
information, amending the SAE data collection tool accordingly.
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
7.4. Reporting Adverse Eventsand Serious Adverse Events
AE Reporting to GSKCH:
AEs will be recorded in the AE section of the CRF. 
Medical conditions recorded by the subject ona 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. 
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 follow-up visits:  
“Have you felt unwell, experienced any symptomsor taken any medication (since 
your last visit) (today) (since your last application) (since the last session)?”
The medically qualified investigator should review adverse events in a timely 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 48 of 65

manner; this review should be documented in writing in the source document or in the 
CRF. 
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 toexisting 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.
Serious Adverse Events to:
Brazil Clinical Study Manager(Rafaela Ross):
Tel: 
E-mail: 
Pharmacovigilance (Brazil)  Fax Number: 
The GSKCH Study Manager 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.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 49 of 65
PPD
PPD
PPD

The initial report will be followed up withmore information as relevant, or as 
requested by the GSKCH study manager.
7.5. Follow-up of Adverse Eventsand Serious Adverse Events
Follow-up of AEs and SAEs:
After the initial report, the investigator is required to proactively follow up with each 
subject and provide further information on the subject’s condition.
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.  
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.
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 has been discharged from the study, and considers the event reasonably 
related to the investigational product or study participation, the investigator will 
promptly notify GSKCH.
The investigator will submit any updated SAE data to GSK within the designated 
reporting time frames.
Regulatory and ethics reporting requirements for SAEs:
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 
responsibility to 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.
GSKCH will comply with country specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBand investigators.
Investigator safety reports are prepared according to GSKCH policy and are 
forwarded to investigators as necessary.  An investigator safetyreport is prepared for 
a SAE(s) that is both attributable to investigational product and unexpected.  The 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 50 of 65

purpose of the report is to fulfill specific regulatory and GCP requirements, regarding 
the product under investigation.
An investigator who receivesan 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 
IRB, if appropriate according to local requirements.
7.6. Collection of Pregnancy Information
7.6.1. Time Period for Collectingof Pregnancy Information
Collection of Pregnancy Information:
Pregnancy information will be collected on all pregnancies reported following 
administration of any test product.Information on a pregnancy identified during the 
screening phase and prior to test product administration does not need to be collected
7.6.2. Action to be Taken ifPregnancy Occurs
Action to be Taken:
The investigator will collect pregnancy information on any subject who becomes 
pregnant while participating in the study after administration of the test product. The 
investigator will record pregnancy 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.
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.
A spontaneous abortion is always considered to be an SAE and will be reported as 
such. An SAE occurring 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.
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.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 51 of 65

If the subject becomes pregnant during the study they should be withdrawn from the 
study and this should be recorded in the appropriate section of the CRF.
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. hospital records, clinical and office charts, laboratory 
notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing 
records, recorded data from automated instruments, microfiches, photographic 
negatives, microfilm or magnetic media, x-rays, subject files and records kept at the 
pharmacy, at the laboratory and at the medico-technical departments involved in the 
clinical study) which contain the source of data recorded in the CRF should be 
specified in the Source Document Designation Form.  In some cases the CRF 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
A CRF is a printed, optical, or electronic document designed to record all of the 
protocol required information to be reported to thesponsor on each trial subject.
For each subject who has given informed consent/assent and has been screened, CRF 
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 
(PII) (including the subject
's name or initials or birth date) is to be recorded in the 
CRF or as part of the query text.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 52 of 65

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 CRFs and transmitted electronically 
to GSKCH in a validated (21 CFR Part 11 compliant) web-based electronic data 
capture system (InForm
TM).
All CRF pages should be completed during a subject assessment when the CRF has 
been designated as the source.  Data that is sourced elsewhere should be entered into 
the CRF in an agreed upon timeframe between the Investigator and Sponsor.  
The CRFs (including queries, query responses and audit trails) will be retained by 
GSKCH. Site data archived compact discs (CD(s)) prepared 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 qualityand 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 CRF 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 CRFs 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 CRFs, to raise 
manual queries as needed for site clarification or correction
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 53 of 65

9. STATISTICAL CONSIDERATIONS AND DATA 
ANALYSES
9.1 Sample Size Determination
Approximately 40 healthy subjects will be screened to randomise at least 30 subjects 
to ensure at least 25 evaluablesubjects complete the entire study. This sample size is 
standard in clinical testing practices and is consistent with theANVISA guidelines 
(ANVISA, 2012).
9.2. General Considerations
9.2.1. Definition of Analysis Populations
The ‘Intent to treat’(ITT) population includes all subjects who are randomised into 
the study and have skin irritation scores from at least one of the test sites available.
A separate Per Protocol (PP) analysis will not be performed. Protocol deviations will 
however be listed for review.
The Safety population includes all subjects who received any studyproduct. All 
safety analyses will be performed using the Safety population.
9.2.2. Exclusion of Data from Analysis
No data will be excluded from any analysis.
9.2.3. Criteria for Evaluation
The primary evaluation will be to assess the phototoxicity and photosensitisation
potentialof the test and control product, based on the irritation (dermal response) and 
superficial irritation (other effects) score/grade after patch removal during the 
induction and challenge phase using the ITT population. 
Safety and tolerability will be evaluated by adverse events assessments using the 
Safety population.
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.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 54 of 65

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.
9.3.1. Demographic and Baseline Characteristics
Age will be summarized using descriptive statistics such as means, medians and 
standard deviations. Gender, race and Fitzpatrick skin type will be summarized using 
frequency counts and percentages
9.3.2. Primary Analysis(es)
The primary analysis will be based on the irritation (dermal response) and superficial 
irritation (other effects) scores/grades assessed using the scales described in Tables 1 
and 2 of Appendix 2. Individual observations will be assessed based on these scales 
and a narrative description of all skin responses, both in the induction and challenge 
phases, will be provided.  
No formal statistical inference will be performed. 
The number and percentage of subjects recording each category of score/grade, as 
well as any skin response versus those without any skin response will be presented by 
treatment group at each assessment time point and over the induction and challenge 
phases using the maximum grade/score across time points. If there are subjects with 
non-zero dermal response or other effects scores, then the dermal response, other 
effects and a combined dermal and others effects score will be summarised using 
descriptive statistics at each assessment time point and over the induction and 
challenges phases using the total score across time points.
9.3.3. Safety Analysis(es)
Adverse Events (AE) will be tabulated according to the current version of the 
MedDRA. Frequencies and percentages will be presented overall, for each system 
organ class, and for each preferred term. Summaries of treatment-emergent AEs, 
treatment-related AEs, AEs leading to discontinuation, and serious AEs will be 
completed. For treatment-related or treatment skin site related AEs, these will also be 
presented by product/test site.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 55 of 65

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 
(GCP)and all applicable subject privacy requirements.  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 the IRB 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 tosubjects. 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 tobe 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 IRB)
4. GSK will provide full details of the above procedures, eitherverbally, 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 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 56 of 65

the study to review with the site staff the protocol, study requirements, and their 
responsibilities to satisfy regulatory, ethical, and GSK requirements.
When reviewing data collection procedures, the discussion will include identification, 
agreement and documentation of data items for which the CRF 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 
regulatory agencies 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 GSKCHStandard 
Operating Procedures.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 57 of 65

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. For multicenter studies (if 
applicable), this can occur atone or more or at all sites.  
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/ 
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 IRB, and should provide the sponsor and the IRBa detailed written 
explanation of the termination or suspension.
2. If the GSKCH terminates or suspends a trial, the investigator should 
promptly inform the IRBand provide the IRBa detailed written 
explanation of the termination or suspension. 
3. If the IRBterminates 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 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 58 of 65

there is an acceptable back-up of these reproductions and that an acceptable quality 
control process exists for makingthese reproductions.
The investigator must assure that the subject’s anonymity will be 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 not for submission 
to GSKCH, e.g. subjects’ written consent forms, should be maintained by the 
investigator in strict confidence.
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 bein accordance with GSK Policy.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 59 of 65

A manuscript will be progressed for publication in the scientific literature if the 
results provide important scientific or medical knowledge.
11. REFERENCES
ANVISA, Guideline for the Safety Evaluation of Cosmetics Products, 2012
ANVISA; Resolution 79/00, Annex XXI and its updates
Basketter, D. A., York, M., McFadden, J. P. and Robinson, M. K. (2004), 
Determination of skin irritation potential in the human 4-h patch test. Contact 
Dermatitis, 51:1–4
Birmingham, J. Clinical Aspects of Cutaneous Irritation and Sensitization, Toxicology 
and Applied Pharmacology 7:(54-59)
Bruze, M Recommendation of appropriate amounts of petrolatum preparation to be 
applied at patch testing* Contact Dermatitis 2007 0105-1873, 56(5):281
Dooms-GoossensA. Cosmetics as causes of allergic contact dermatitis. Cutis 1993; 
52: 316-320.
Dooms-Goossens, A, Corticosteroid contact allergy: an EECDRG Multicenter study
Contact Dermatitis, 1996, 0105-1873, 35(1):40
Draize JH, Methods for the study of irritation and toxicity of substances applied 
topically to the skin and mucous membranes Journal ofPharmacology and 
Experimental Therapeutics, 1944, 0022-3565, 82(3):377
Edward, M. Jackson, and FMT Robillard Norman. "The controlled use test in a 
cosmetic product safety substantiation program." Journal of Toxicology: Cutaneous 
and Ocular Toxicology 1.2(1982): 117-132.
European Commission (EC) Regulation No 1223/2009of the European Parliament 
and of the Council of 30 November 2009on cosmetic products
Fitzpatrick TB, Pathak M, Parrish JA. Protection of human skin against the effects of 
the sunburn ultraviolet (290-320 nm). In: Fitzpatrick TB et al. (eds). Sunlight and 
man, normal and abnormal photobiological responses. Tokyo, p. 751-755.
Fitzpatrick, T.B., The validity and practicability of sun-reactive skin types I through 
VI.Arch. Dermatol.124, pp. 869-871, 1988
Food and Drug Administration. ICH Topic E6: Guideline for Good Clinical Practice.  
Fed Reg1997; 62(90):25691-709.
Guidance for Industry; Skin Irritation and Sensitisation Testing of Generic 
Transdermal Drug Products, U.S. Department of Health and Human Services
Food and Drug Administration Center for DrugEvaluation and Research (CDER) 
Federal Register. 1999;64(38):9516. 
Hasan T, Photopatch test reactivity: effect of photoallergenconcentration and UVAA 
dosaging, Contact Dermatitis, 1996, 0105-1873, 34(6):383
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.
Isaksson, M., GrUVAberger, B., Frick-Engfeldt, M. and Bruze, M. (2007), Which test 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 60 of 65

chambers should be used for acetone, ethanol, and water solutions when patch testing? 
Contact Dermatitis, 57:134–136. doi:10.1111/j.1600-0536.2007.01094.x
LachapelleJ.-M., Maibach H. I, Patch Testing and Prick Testing, A practical Guide 
Official Publication of the ICDRG, 3rdEdition, 2012
Lee E, An S, Choi D, Moon S, Chang I. Comparison of objective and sensory skin 
irritations of several cosmetic preservatives. Contact Derm2007; 56: 131-6.
McNamee PM, Api AM, Basketter DA, et al.A review of critical factors in the 
conduct and interpretation of the human repeat insult patch test. Regul Toxicol 
Pharmacol2008; 52: 24-34.
NationalHealthSurveillance AgencyBrazil (ANVISA). Guideline for the Safety 
Evaluation of Cosmetic Products.Brasília; 2012.
Neumann NJ, Evaluation of phototoxic and photoallergic potentials of 13 compounds 
by different in vitro and in vivo methods, Journal of Photochemistry and Photobiology 
C: Photochemistry Reviews, 2005, 79(1):25
Spiewak R. Patch testing for contact allergy and allergic contact dermatitits. Open 
Allergy J2008; 1: 42-51.
Walberg JE, Magnus L. Patch testing. In:Frosch PJ, Mene T, Lepoittevin J-P, eds. 
Contact Dermatitis. 4
thedition.Berlin: Springer. 2006; 365-90. 
Wilkinson, D. S., et al. "Terminology of contact dermatitis." Acta Derm Venereol 
50.4 (1970): 287-292.
World Medical Association Declaration of Helsinki, 59thGeneral Assembly, Seoul 
2008.
Zatz JL. Skin Permeation: fundamentals and application. Wheathon, Allured 
Publishing Corporation, 1993.
12. APPENDICES
12.1. Appendix 1 -Abbreviations and Trademarks
Abbreviations
AE 
Adverse Event
aq
Aqueous 
AUC
Area under Curve
CD
Compact Disc
cm
2
Square Centimeter
CRF
Case Report Form
DVD
Digital Versatile Disc
EDC
Electronic Data Capture
EEMCO
European Group for Efficacy Measurements on Cosmetics and Other 
Topical Products
FSFV
First Subject First Visit
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 61 of 65

g
Gram
GCP
Good Clinical Practice
GSK
GlaxoSmithKline
GSKCH
GlaxoSmithKline Consumer Healthcare
hr
Hour(s)
ICF
Informed Consent Form
ICH
International Conference on Harmonization of Technical Requirements 
for Registration of Pharmaceuticals for Human Use
IEC
Independent Ethics Committee
IRB
Institutional Review Board
ITT
Intention to Treat
J
Joules
LSLV
Last Subject Last Visit
m2
Square meter
MedDRA
Medical Dictionary for Regulatory Activities
mg
Milligrams
min
Minute
ml
Milliliters
nm
Nanometers
PII
Personally Identifiable Information
PP
Per Protocol
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
12.2. Appendix 2 -Dermal Response Score 
 
 
 
 
 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 62 of 65
CCI

 
 
 
 
 
 
 
 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 63 of 65
CCI
CCI
CCI
CCI

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12.3.Appendix 3-Fitzpatrick Skin Type Grading
 
 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 64 of 65
CCI
CCI
CCI

 
 
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-Mar-2017 13:44:28
 
Clinical Operations Approval
24-Mar-2017 07:31:50
Approved
23-Mar-2017 12:21:29
Biostatistics Approval
Approved
Clinical Protocol 207587
23-Mar-2017 11:04:34
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-Mar-2017 07:31:59
 
eldo_clinical_doc
2.0; Most-Recent; Effective; CURRENT
Clinical Protocol 207587
Auto Issue
090032d580d16e68
Page 65 of 65
PPD
PPD
PPD
PPD