A Clinical Study to Assess the Cutaneous and Ocular Local Tolerance of Two Cosmetic Facial Cleansers in Healthy Females With Sensitive Skin Under Normal Conditions of Use
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  An unpublished work subject to trade secret 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
207782
 
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CONFIDENTIAL
SUMMARY INFORMATION
Title:
A Clinical Study to Assess the Cutaneous and Ocular 
Local Toleranceof TwoCosmetic Facial Cleansersin 
Healthy Femaleswith Sensitive Skin Under Normal 
Conditions of Use.
Protocol Number:
207782
Sponsor:
GlaxoSmithKline Consumer Healthcare (GSKCH)
Rua Hungria, 1240 4º andar, Jardim Europa
São Paulo/SP –Brazil, CEP 01455-000
Tel: 
Product Name:
Micellar Cleanser
Micellar Foaming Cleanser
Development Phase:
N/A
Expert Advice Outside of Normal 
Working Hours:
Tel: 
 (US)
Key ProtocolAuthors:
PRIMARY CONTACT
Clinical Study Manager:
, MSc
GlaxoSmithKline Consumer Healthcare 
(GSKCH)
St. Georges Avenue, Weybridge, Surrey, 
KT13 0DE. UK
Tel. 
PRIMARY CONTACT
Clinical Study Manager:
 
Consumer Healthcare (GSKCH)
Rua Hungria, 1240 4º andar, Jardim 
Europa
São Paulo/SP –Brazil, CEP 01455-000
Tel: 
Biostatistician:
, MSc
Other Protocol Authors:
Clinical Supplies:
Data Manager:
Medical Expert:
, MD, Ph.D
 
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Principal Investigator:
Mariane Martins Mosca -Biologist
Study Site Name & Address:
ALLERGISA Pesquisa Dermato-
Cosmética Ltda , Av. Dr. Romeu 
Tórtima, 452/466 –Barão Geraldo –
Campinas –SP –Zipcode: 13084-791
Study Site Telephone Number:
Ophthalmologist: 
Study Ophthalmologistwill be assigned 
according to the site schedule (before 
Baseline Visit) and documented in the 
site file.
Dermatologist:
Study Dermatologistwill be assigned 
according to the site schedule (before 
Baseline Visit) and documented in the 
site file.
 
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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 and the Declaration of Helsinki.
Investigator Name:
Investigator Qualifications:
Investigator Signature:
Date of Signature/ Agreement:
 
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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
PROTOCOL SYNOPSIS FOR STUDY 207782...................15
1. INTRODUCTION...............................................................21
2. OBJECTIVE(S) AND ENDPOINT(S)...............................23
3. STUDY PLAN.....................................................................23
3.1. Study Design.......................................................................23
3.2. Subject Restrictions...........................................................25
3.3. Type and Planned Number of Subjects............................27
3.4. Study Design and Application Amount Justification.......28
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.........................................33
4.5. Subject Replacement..........................................................34
4.6. Subject and Study Completion..........................................34
5.PRODUCT INFORMATION.............................................34
5.1. Study Product.....................................................................34
5.2. Application Schedule.........................................................35
 
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5.3. Product Assignment...........................................................36
5.3.1 Randomization...................................................................36
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. Contact Lens Wearer Status Assessment.........................39
6.1.5. Inclusion / Exclusion Criteria...........................................39
6.1.6. Medical History and Concomitant Medication...............40
6.1.7.Lactic Acid Stinging Test..................................................40
6.1.8. Subject Eligibility..............................................................41
6.2 Visit 2 –Baseline Visit.........................................................41
6.2.1. Inclusion / Exclusion Criteria...........................................41
6.2.2. Medical History and Concomitant Medication...............41
6.2.3. Fitzpatrick Skin Type Assessment...................................41
6.2.4. Skin Type Assessment.......................................................41
6.2.5. Dermatologist Assessment................................................41
6.2.6. Ophthalmologist Assessment............................................42
6.2.7. Subject self-assessment.....................................................42
6.2.8. Subject Eligibility..............................................................43
6.2.9. Supervised Product Application.......................................43
6.3. Visit 3 -Last Subject Last Visit (LSLV) and Study 
Conclusion........................................................................43
6.3.1. Diary Review.....................................................................44
 
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6.3.2. Study Conclusion...............................................................44
7. SAFETY ASSESSMENTS..................................................44
7.1. Definitions of an Adverse Event and Serious Adverse 
Event.................................................................................44
7.1.1. Adverse Events..................................................................44
7.1.2. Serious Adverse Events.....................................................46
7.2. Recording Adverse Events and Serious Adverse Events.47
7.3. Evaluating Adverse Events and Serious Adverse Events47
7.4. Reporting Adverse Events and Serious Adverse Events..49
7.5. Follow-up of Adverse Events and Serious Adverse Events
..........................................................................................50
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............................................53
8.3. Data Handling....................................................................53
8.3.1. Data Queries......................................................................54
8.4. Processing Patient Reported Outcomes............................54
9. STATISTICAL CONSIDERATIONS AND DATA 
ANALYSES....................................................................54
9.1 Sample Size Determination.................................................54
9.2. General Considerations.....................................................55
9.2.1. Definition of Analysis Populations...................................55
9.2.2. Exclusion of Data from Analysis......................................55
9.2.3. Criteria for Evaluationof Local Tolerance.....................55
9.2.4. Criteria for Assessing Safety............................................55
 
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9.2.5. Handling of Dropouts and Missing Data.........................55
9.3. Statistical Methods and Analytical Plan...........................56
9.3.1. Demographic and Baseline Characteristics.....................56
9.3.2. Primary Analysis(es).........................................................56
9.3.3. Secondary Analysis(es).....................................................56
9.3.4. Safety Analysis(es).............................................................57
10. STUDY GOVERNANCE CONSIDERATIONS.............57
10.1. Posting of Information on Publicly Available Clinical 
Trials Registers................................................................57
10.2. Regulatory and Ethical Considerations, Including the 
Informed Consent............................................................57
10.3. Quality Control (Study Monitoring)...............................58
10.4. Quality Assurance............................................................58
10.5. Conditions for Terminating the Study............................59
10.6. Records Retention............................................................59
10.7. Provision of Study Results to Investigators, Posting of 
Information on Publicly Available Clinical Trials 
Registers and Publication................................................60
11. REFERENCES..................................................................62
12. APPENDICES...................................................................63
12.1. Appendix 1 -Abbreviations.............................................63
12.2. Appendix 2 -Fitzpatrick Skin Type Grading.................64
12.3. Appendix 3 -Dermal Response Score.............................64
12.4. Appendix 4 –Ocular Response Score.............................65
12.5. Appendix 5 -Subject Self-Assessment Score..................66
 
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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 IRBin 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.
 
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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. 
Tohighlight the change, the following features will be used: 
To addtext: Use of CAPITAL LETTERS, BOLD AND UNDERLINE
To delete text: Use of Strikethrough e.g. strikethrough
Amendment 
No. & New 
Protocol 
Version No.
Type of 
Amendment
Reason for Amendment
Other Documents 
Requiring 
Amendment
Section(s) Amended 
PI 
Amendment 
Agreement
Signature & 
Date
Amendment 
No.:1
Non-
Substantial/Minor    
Clarification to Inclusion 
and Exclusion criteria to be 
assessed Visit 2 by 
appropriately qualified 
members of staff.
Removal of duplication of 
assessment at Visit 3
Clarification to detail: a 
Informed Consent   
Yes No
Safety Statement     
Yes No
CRF                       
Yes No
Schedule of Events
Synopsis –Study Design
3.1 Study Design
4.1 Inclusion Criteria
4.2 Exclusion Criteria
6.1.5 Inclusion/Exclusion 
Criteria (Visit 1)
6.2.1 Inclusion/Exclusion 
Criteria (Visit 2)
Synopsis –Study Design
3.1 Study Design
3.4 Study Design and 
Signature:
Protocol 
Version 
No.:
Substantial/ 
Major          
Date:
 
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combined score of at least 2 
for the lactic Acid Stinging 
test outcomeis needed.
Additional text to clarify the 
4 randomisation strata to be 
used.
Correctionto which visitthe 
Subject Self-Assessment 
Questions will be asked.
Application Amount 
Justification
6.1.7 Lactic Acid Stinging 
Test
5.3.1 Randomization
12.5 Appendix 5
Amendment 
No.:
Non-
Substantial/Minor    
Informed Consent   
Yes No
Safety Statement     
Yes No
CRF                       
Yes No
Signature:
Protocol 
Version 
No.:
Substantial/ 
Major           
Date:
 
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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.:
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:
 
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SCHEDULE OF EVENTS
Procedures
Visit 1
Screening 
Visit 2
Baseline
Visit 3
(21(+ 2)Days)
Informed consent 
X
Demographics
X
Medical History
X
Current/Concomitant Medicationsreviewed
X
X
X
InclusionandExclusion criteria
X
Xa
Fitzpatrick Skin Type Assessment 
X
Contact Lens Wearer Status Assessment
X
Skin Type Assessment by Dermatologist (Dry or Normal/Combination)
X
Clinical Assessment by Dermatologist b
X
X
Clinical Assessment by Ophthalmologist c
X
X
Clinical Diagnosis of Sensitive Skin Confirmed by Lactic Acid Stinging Test
X
Subject Self-Assessment Questions
Xd
X
Subject Eligibility
X
Continued Eligibility
X
X
Randomization & Stratification 
X
Product Dispensing (including Diary Cardand Instructions for Use)
X
Supervised First Product Application
X
Return Product and Diary Cardand Instructions for Use
X
Adverse Event Assessment 
e
X
X
X
Study Conclusion and Exit
X
 
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NOTE: Visit 2 should be scheduled within 7 days of the Screening visit (Visit 1).
a. Inclusion Criteria 5A, 5c, 5d and 5e and Exclusion Criteri
a 7Band 7f will be assessed at 
Visit 2.
b. A qualified dermatologist will perform assessments for subject eligibility to participate 
in the study prior to any product applicationat Visit 2, in addition to assessments 1-hour 
(± 20minutes) post first supervised product application and at Visit 3following 3 weeks 
of product home use, using the scoring system detailed in Appendix 3.
c. A qualified ophthalmologist will perform assessments for subject eligibility to 
participate in the study prior to product applicationat Visit 2, in addition to assessments 
1-hour (± 20minutes) post first supervised product application and at Visit 3following 
3 weeks of product home use, using the scoring system in Appendix 4.
d. Subject Self-Assessment questions (Appendix 5) will beasked at Visit 2, BEFORE first 
product applicationand 1-hour (± 20minutes)post supervised product application.
e. Adverse events will be captured following the lactic acid stinging test procedure.
 
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PROTOCOL SYNOPSIS FOR STUDY207782
Brief Summary
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).
Acceptability studies seek to prove in real conditions of use the absence of primary and/or 
accumulated irritation in normal conditions of use (ANVISA, 2012).
Theobjectiveof this clinical studyis to assess the cutaneous and ocular local toleranceof 
two cosmetic facial cleansersin healthy femaleswith sensitive skin under normal 
conditions of use. 
Objective(s) and Endpoint(s)
Objective(s)
Endpoint(s)
Primary
Assessment ofthe cutaneous and ocular 
tolerance of two cosmetic facial cleansers 
after 21 (+ 2) days of product use per the 
intended instructions in healthy female
subjects with clinically assessedsensitive 
skin.
Dermatologist and ophthalmologist visual 
assessment of cutaneous and ocular 
irritation after 21 (+ 2)days of test product 
use.
Secondary
Assessment of the cutaneous and ocular 
tolerance of two cosmetic facial cleansers 
after 21 (+ 2) days of product use per the 
intended instructions in healthy female
subjects with clinically assessed sensitive 
skin.
Subject self-assessment question responses 
(redness, dryness, burning, itching and 
stinging) with regards to product use 
experienceonthe face and around the eyes 
after 21 (+ 2) days of test product use.
To evaluate the general safety of two 
cosmetic facial cleansers
Frequency and severity of Adverse Events
Study Design
Overall Design
This is an assessor blind (dermatologist and ophthalmologist) clinical in use study to 
determine the local cutaneous and ocular tolerance of two cosmetic facial cleanser products 
when used as per the intended instructions for use in a population of healthy female 
 
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subjects with clinically assessed sensitive skin.
Subjects who have sensitive skin as classifiedby a positive reaction to a lactic acid 
Stinging Test will be asked to use one of two cleansing products as part of their normal 
skin care routine for 3 weeks.
Both test products are the same formulation but are differentiated by the dispensing pack; 
to either a micellar cleanser or a foaming cleanser.
Subjects will be instructed to cleanse their face with one of the twotest products at home 
twice-daily,for 21(+2) days, including a supervised first application at the study site 
(Visit 2) and a final application at home on the morning of the final visit (Visit 3), as per 
the intended instructions for use.
A qualified dermatologist and a qualified ophthalmologist will assess the baseline 
cutaneous an ocular irritation of prospective subjectsat Visit 2. For a subject to be 
considered eligible to participate in the study, alldermatologist and ophthalmologist 
assessment scores must be zero. Further dermatologist and ophthalmologist assessments 
will be completed 1-hour (± 20minutes)post supervised first product useand at the final 
visit (Visit 3) at the end of the 21 (+2) dayproduct use period. The intensity of any visual 
signs of cutaneousand ocular irritation will be recorded by the dermatologist and 
ophthalmologist, according to the assessment scales detailed in Appendix 3 and 4.
The dermatologist will also determine eachsubject’s facial skin typeas dry, oily or 
normal/combination skin. Any subject classified as having oily skin will not be considered
eligible for participation in the study as they do not represent the target population for the 
product.
Subjects will be asked to complete self-assessment questionsat Visit 2prior to any study 
product use. In addition, randomized subjects will be asked to complete the self-
assessment questions 1hour (± 20minutes)post supervised first product use and at the end 
of the 21 (+2) dayproduct use period.
Theobjectiveof this clinical study is to assess the cutaneous and ocular local toleranceof 
two cosmetic facial cleansersin healthy femaleswith sensitive skin under normal 
conditions of use. 
Visit 1–Screening Visit
The following assessments will be conducted:
1. Subject Informed Consent taken
 
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2. Subject demographicscollected
3. Medical history details collected
4. Details of current and concomitant medicationcollected
5. Inclusion/Exclusion criteria 
6. Contact lens wearer status assessment (Yes or No)
7. Clinical diagnosis of sensitive skin confirmed by Lactic Acid sting test 
8. Determination ofsubject eligibility to participate in the study
9. Adverse events will be reported following the Lactic Acid stingingtest procedure
Visit 2 –Baseline Visit
Within 7 days of the Screening Visit
The following assessments will be conducted:
1. Current/Concomitant medicationsreview
2. INCLUSION/EXCLUSION CRITERIA
3. Fitzpatrick skin type assessment (Appendix 2) 
4. Dermatologist assessment of skin type status (dry, oily or normal/combination) 
Inclusion criteria 5e and Exclusion criteria 7f
5. Clinical dermatologist assessment for eligibility to participate in the study 
(including visual examinations)(Appendix 3). Inclusion criteria 5c
Note:subject must have a total score of zero for inclusion into the study
6. Clinical ophthalmologist assessment for eligibility to participate in the study 
(including visual examinations)(Appendix 4). Inclusion criteria 5d
Note:subject must have a total score of zero for inclusion into the study.
7. Subject self-assessment questions(Appendix 5). Prior to product use.
8. Continued eligibility check
9. Randomization and stratification
10.Dispense assigned study product and diary card/instructions for use
11.Supervised first use of assigned product
12.Dermatologist (Appendix 3) and ophthalmologist (Appendix 4) assessments1hour 
(± 20 minutes) post supervised first product application
13.Subject self-assessment questions(Appendix 5)1hour (± 20 minutes) post first 
supervised use
14.Adverse events assessment
Visit 3 -Week 3 / Exit from Study(21 (+ 2) Days)
The following assessments will be conducted:
1. Current/Concomitant medicationsreview
2. Continued eligibility check
3. Return study product and diary card/instructions for use
4. Diary card check to confirm compliantproduct use
5. Dermatologist final assessment of tolerance (Appendix 3)
 
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6. Ophthalmologist final assessment of tolerance (Appendix 4)
7. Subject final self-assessment questions (Appendix 5)
8. Return assigned cleanser and Diary Card/Instructions for use
9. Adverse event assessment
10.Subject discharge from the study site following completion of all study procedures
Type and Planned Number of Subjects
Healthy female subjects, aged 18 to 65years with sensitive skin and no dermatological or 
ophthalmological disorders will be enrolled into this study. Female subjects with sensitive 
skin have been selected as they are the target consumersfor the finished product with 
greater familiarizationand habitual use of facial cleanser products. Prospective subjects 
shall be frequent users of make-up, including eye make-up.
Subjects with sensitive skin as determined byapositive response to the lactic acid Stinging 
Test will be considered eligible to participate in the study. Subjects with a Fitzpatrick 
phototype I to IV will be recruited to ensure any reactions are clearly visible on subject’s 
skin. In addition to subjects who have a positive responseto the lactic acid Stingingtest, 
eligible subjects will have skin type assessed by aqualified dermatologist, and only 
subjects with dry or normal/combination skin will be considered eligible to participate in 
the study. Subjects with oily skin will not be enrolled as they do not represent the target 
population for the test products. 
A sufficient number of subjects will be screened (up to170) to randomize at least92
subjects (46per treatment group) toensure that at least 40subjectsin each treatment group 
completethe study(80 subjects in total). 
Randomization will be stratified by both contact lens wearer status(yes or no) and skin 
type (dry or normal/combination)to ensure that an equal population of contact lens wearers 
and skin type(dryor normal/combination) is randomized to each treatment.
The sample size is based on clinical considerations to provide descriptive information on 
the local toleranceand safety of the test products and is consistent with ANVISA 
guidelines (ANVISA, 2012).
Diagnosis and Main Criteria for Inclusion
Healthy female subjects aged 18 to 65 years with dry or normal/combination dermatologist 
assessed skin, no dermatological or ophthalmological disorders, Fitzpatrick skin phototype 
 
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I to IV and a positive response to a lactic acid Stinging Test will be considered eligible to 
participate in this study.  
Product Information
Test Product 1
Test Product 2
Product Name
Micellar Cleanser
Micellar Foaming 
Cleanser
Product Formulation Code 
(MFC)
Product Format
200ml Clear plasticbottle
150ml Plasticpump pack
Application Quantity
To be used as per normal home use application
Route of Administration
Topical dermal application
Application Instructions
Use morning and evening. 
Apply to a cotton pad and 
wipe over the entire face 
and closed eyes to gently 
cleanse. 
No need to rub or rinse. 
Cotton pads will be 
supplied. *
Use morning and 
evening.
Massage gently onto wet 
skin on the faceusing 
fingertips, rinse 
thoroughly and pat skin 
dry.
*Cotton padswill additionally be suppliedby the study site
Statistical Methods
The focus of the statistical analysis will be the evaluationof the frequency of cutaneous and 
ocular reactionresponseswith each test product.
For the primary endpoints, individual observations willbe assessed based on Appendix 3
and Appendix 4and a narrative description of all cutaneous and ocular responses will be 
provided.  A frequency tabulation of the number of subjects with any cutaneous and ocular 
response versus those without any cutaneous and ocular response for each assessment will 
be presented at each time point for each of the test products. If there are subjects with non-
zero response scores, a combined skin (sum of dermal and superficial irritation) score, and 
a combined ocular (sum of conjunctiva and lacrimal) score at each time-point and for the 
sum across time points following product use (sum of Baseline (Visit 2)and Visit 3) will be 
determined and summarised using descriptive statistics. 
For the secondary endpoints, each subject assessment (redness, dryness, burning, itching
and stinging, as per Appendix 5) and combined score (summed across these 5 assessments) 
 
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CCI

will be similarly presented at each time point and for the sum across time points following 
product use (sum of Baseline (Visit 2)andVisit 3) for each of the test products.
Data will also be presented by sub-groups, contact lens wearer status (yes, no) and skin 
type (dry, normal/combined) at baseline.
No interim 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 for each of the 
test products. Summaries of treatment-emergentAE’s, treatment-related AE’s, and AE’s 
leading to discontinuation, and serious AE’s will be presented.
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.  
 
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1. INTRODUCTION
In recent years the cosmetic industry has grown considerably, along with its concernfor 
developing safe and effective products. This industry awareness, consumerand regulatory 
agency requirements have led cosmetic manufacturers to adoptprocedures 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, increasingtheir credibility andconfidence 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, theraw 
materials used in the product formulation must be of proven safety and withestablished use 
in the cosmetic industry. As a general requirement, the safety of thefinal formulation must 
also be confirmed before it is marketed.
Cleansers are designed to remove dirt, sweat, sebum and oils from the skin. This is 
achieved through the use of surfactants that aid in the uplifting of dirt and solubilisation of 
oils. However, the interaction of cleansers and the stratum corneum can be detrimental to 
the skin, causing tightness and dryness as well as barrier damage, erythema, irritation and 
itch (Wihelm, 1994).
Skin contact with topical products such as cosmetics may trigger different types of 
reactions including eczematous,contact dermatitis, urticaria, acne and spots.  Contact 
dermatitis can arisefrom two mechanisms: primary irritation,through the action of irritant 
substances; or sensitization, in the presence of anallergenic ingredient (Birmingham, 
1965).
Clinical studiesto evaluate the irritation and sensitisation potential of a product must take 
intoaccount a number of variablesincluding thecomponents used in the formulation, 
ingredientconcentration, absorption, amount applied, skin condition, application directions 
andfrequency, aswell as the cumulative effect (Dooms-Goossens, 1993).The most 
common form of intolerance to cosmetics is characterized by irritation, burning sensation, 
redness, pruritus and erythema at the application site (Lumelsky et al., 2001). 
Acceptability studies aimto determine the irritationpotential of cosmetic products under 
normalconditions of use, to provide data to support the local tolerance profile in the target 
population prior to commercialization. 
 
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Sensitive skin isregarded as a non-inflammatory response to products applied on the skin, 
and it is characterized by a sensorial reaction such as stinging, burning or itching, but with 
no visible irritation-related skin changes and with no immune response. This reaction often 
occurs onthe faceand may also be referred to assensorial orsubjective contact dermatitis 
or cosmetic intolerance syndrome, and is defined as elevated intolerance totopically 
appliedsubstances, such as cosmetics and products for skin treatment. It has been verified 
that people with sensitive skin are prone to developing irritant or allergic contact dermatitis 
(Farage et al., 2006). 
Some substances may trigger an irritant response in sensitive skin, such as benzoic acid, 
cinnamic acid, non-ionic emulsifiers, sodium lauryl sulfate, bronopol, lactic acid, propylene 
glycol, urea and sorbic acid (De Groot et al., 2010;Lundov et al., 2010
). A widely used 
reactivity test to determine sensitivity toirritation is a stinging test, where lactic acid is
applied tothe nasolabial foldin order to induce a sensorial response. The stinging sensation 
to the irritant may be measured in a binary way (i.e. presence or absence) or with a 
magnitude scale (Farageet al., 2006).
In general, facial skin types are classified into three types according to asubjective 
judgment, as: oily, normal, or dry. Relatively recently, another facial skin type has been 
added to these skin types, the combination skin type, which means that the individual 
shows regional differences in type (Youn 2005).
Subjects with a dermatologist assessed skin type ofdry or normal/combination will be 
considered eligible to participate in this study. Dry skin is skin that produces less sebum 
thannormal skin and as a result lacks lipids to maintain a healthy moisture barrier, it has a 
course feel and roughness whichlooks dull in appearance. Normal/combination skin is a
term to described balanced skin, fine pores, good blood circulation, soft, smooth texture, 
and no blemishes or skin with a combination of skin types across the face from oily in the 
‘T-zone’(forehead, chin and nose) to normal to dry on the cheeks, enlarged pores in some 
areas, with some impurities.
Theobjectiveof this clinical study is to assess the cutaneous and ocular local toleranceof 
two cosmetic facial cleansersin healthy femaleswith sensitive skin under normal 
conditions of use.
 
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2. OBJECTIVE(S) AND ENDPOINT(S)
Objective(s)
Endpoint(s)
Primary
Assessment of the cutaneous and ocular 
tolerance of two cosmetic facial cleansers 
after 21 (+ 2) days of product use per the 
intended instructions in healthy female
subjects with clinically assessed sensitive 
skin.
Dermatologist and ophthalmologist visual 
assessment of cutaneous and ocular 
irritation after 21 (+ 2) days of test product 
use.
Secondary
Assessment of the cutaneous and ocular 
tolerance of two cosmetic facial cleansers 
after 21 (+ 2) days of product use per the 
intended instructions in healthy female
subjects with clinically assessed sensitive 
skin.
Subject self-assessment question responses 
(redness, dryness, burning, itching and 
stinging) with regards to product use 
experienceonthe face and around the eyes 
after 21 (+ 2) days of test product use.
To evaluate the general safety of two 
cosmetic facial cleansers.
Frequency and severity of Adverse Events
3. STUDY PLAN
3.1. Study Design
Overall Design
This is an assessor blind (dermatologist and ophthalmologist) clinical in use study to 
determine the local cutaneous and ocular tolerance of two cosmetic facial cleanser products 
when used as per the intended instructions for use in a population of healthy female 
subjects with clinically assessed sensitive skin.
Subjects who have sensitive skin as classified by a positive reaction to a lactic acid 
Stinging Test will be asked to use one of two cleansing products as part of their normal 
skin care routine for 3 weeks.
Both test products are the same formulation but are differentiated by the dispensing pack; 
to either a micellar cleanser or a foaming cleanser.
Subjects will be instructed to cleanse their face with one of the twotest products at home 
twice-daily,for 21(+2) days, including a supervised first application at the study site 
(Visit 2) and a final application at home on the morning of the final visit (Visit 3), as per 
the intended instructions for use.
 
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A qualified dermatologist and a qualified ophthalmologist will assess the baseline 
cutaneous an ocular irritation of prospective subjects at Visit 2. For a subject to be 
considered eligible to participate in the study, all dermatologist and ophthalmologist 
assessment scores must be zero. Further dermatologist and ophthalmologist assessments 
will be completed 1-hour (± 20 minutes)post supervised first product use and at the final 
visit (Visit 3) at the end of the 21 (+2) day product use period. The intensity of any visual 
signs of cutaneousand ocular irritation will be recorded by the dermatologist and 
ophthalmologist, according to the assessment scales detailed in Appendix 3 and 4.
The dermatologist will also determine each subject’s facial skin type as dry, oily or 
normal/combination skin. Any subject classified as having oily skin will not be considered 
eligible for participation in the study as they do not represent the target population for the 
product.
Subjects will be asked to complete self-assessment questions at Visit 2 prior to any study 
product use. In addition, randomized subjects will be asked to complete the self-
assessment questions 1 hour (± 20 minutes)post supervised first product use and at the end 
of the 21 (+2) day product use period.
Theobjectiveof this clinical study is to assess the cutaneous and ocular local toleranceof 
two cosmetic facial cleansersin healthy femaleswith sensitive skin under normal 
conditions of use. 
Visit 1 –Screening Visit
The following assessments will be conducted:
1. Subject Informed Consent taken
2. Subject demographicscollected
3. Medical history details collected
4. Details of current and concomitant medicationcollected
5. Inclusion/Exclusion criteria 
6. Contact lens wearer status assessment (Yes or No)
7. Clinical diagnosis of sensitive skin confirmed by Lactic Acid sting test 
8. Determination of subject eligibility to participate in the study
9. Adverse events will be reported following the Lactic Acid stingingtest procedure
Visit 2 –Baseline Visit
Within 7 days of the Screening Visit
The following assessments will be conducted:
1. Current/Concomitant medicationsreview
2. INCLUSION/EXCLUSION CRITERIA
 
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3. Fitzpatrick skin type assessment (Appendix 2) 
4. Dermatologist assessment of skin type status (dry, oily or normal/combination) 
Inclusion criteria 5e and Exclusion criteria 7f
5. Clinical dermatologist assessment for eligibility to participate in the study 
(including visual examinations)(Appendix 3). Inclusion criteria 5c
Note:subject must have a total score of zero for inclusion into the study
6. Clinical ophthalmologist assessment for eligibility to participate in the study 
(including visual examinations)(Appendix 4). Inclusion criteria 5d
Note:subject must have a total score of zero for inclusion into the study.
7. Subject self-assessment questions(Appendix 5). Prior to product use.
8. Continued eligibility check
9. Randomization and stratification
10.Dispense assigned study product and diary card/instructions for use
11.Supervised first use of assigned product
12.Dermatologist (Appendix 3) and ophthalmologist (Appendix 4) assessments1hour 
(± 20 minutes) post supervised first product application
13.Subject self-assessment questions(Appendix 5) 1 hour (± 20 minutes) post first 
supervised use
14.Adverse events assessment.
Visit 3 -Week 3 / Exit from Study(21 (+ 2) Days)
The following assessments will be conducted:
1. Current/Concomitant medicationsreview
2. Continued eligibility check
3. Return study product and diary card/instructions for use
4. Diary card check to confirm compliant product use
5. Dermatologist final assessment of tolerance (Appendix 3)
6. Ophthalmologist final assessment of tolerance (Appendix 4)
7. Subject final self-assessment questions (Appendix 5)
8. Return assigned cleanser and Diary Card/Instructions for use
9. Adverse event assessment
10.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:
 
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1. Changing any cosmetic habits, including personal hygiene.
2. Addition ofany new cosmetic product to their current regimen or switching 
brandsof facial cosmetic products.
3. Changing dietary habits.
4. Exposure to artificial ultraviolet (UV) light or cosmetic procedures (includes 
tanning beds, Intense Pulsed Light, etc.) on the facefor the duration of the 
study.
5. Introduction ofnew products during the study,including but not limited to
soap, laundry detergent, or fabric softener.
6. If subject is a contact lens wearer, contact lenses should be removed prior to 
product application.
Baseline Visit (Visit 2):
1. Application ofany leave-on cosmetics (e.g. creams, lotions, foundation, 
mascara, eyeliner and concealer) to the face prior to the Baseline Visit (Visit 
2) should be avoided on the day of the visit.
Final Visit (Visit 3):
2. Application ofany leave-on cosmetics (e.g. creams, lotions, foundation, 
mascara, eyeliner and concealer)to the faceshould be avoided on the day of 
the visit.
3. Application of any detergents (e.g. soaps, shampoos, and bath and shower 
products) to the face,other than the dispensed test productshould be avoided
on the day of the visit.
Medications and Treatments
During the entire study (Screening –LSLV) the following medications and 
treatments should be avoided:
1. Aesthetic, cosmetic or dermatological treatment of the face and/or eyes
2. Change inhormone treatment or contraception
 
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3. Use of the following medications:
a. Systemic or topical corticosteroids
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 of the face and or eyes
3.3. Type and Planned Number of Subjects
Healthy female subjects, aged 18 to 65years with sensitive skin and no dermatological or 
ophthalmological disorders will be enrolled into this study. Female subjects with sensitive 
skin have been selected as they are the target consumers for the finished product with 
greater familiarization and habitual use of facial cleanser products. Prospective subjects 
shall be frequent users of make-up, including eye make-up.
Subjects with sensitive skin as determined by a positive response to the lactic acid Stinging 
Test will be considered eligible to participate into the study. Subjects with a Fitzpatrick 
phototype I to IV will be recruited to ensure any reactions are clearly visible on subject’s 
skin. In addition to subjects who have a positive responseto the lactic acid Stingingtest, 
eligible subjects will have skin type assessed by aqualified dermatologist, and only 
subjects with dryor normal/combination skin will be considered eligible to participate in 
the study. Subjects with oily skin will not be enrolled as they do not represent the target 
population for the test products. 
A sufficient number of subjects will be screened (up to170) to randomize at least92
subjects (46per treatment group) toensure that at least 40subjectsin each treatment group 
completethe study(80 subjects in total). 
Randomization will be stratified by both contact lens wearer status (yes or no) and skin 
type (dry or normal/combination)to ensure that an equal population of contact lens wearers 
and skin type(dryor normal/combination) randomized to each treatment.
The sample size is based on clinical considerations to provide descriptive information on 
the local toleranceand safety of the test products and is consistent with ANVISA 
guidelines (ANVISA, 2012).
 
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3.4. Study Design and Application Amount Justification
This is a single center, 2-arm, parallel group, non-comparative, assessor (dermatologist and 
ophthalmologist) blinded study in healthy female subjects withclinically assessedsensitive 
skin, conducted under the supervision of a dermatologist and ophthalmologist, to assess the 
cutaneous and ocular local tolerance of two cosmetic facial cleanserswhen used for a 
period of 21 (+2) days as per the intended instructions for use.
A lactic acid stingingtest will be used to confirm whether a subject has sensitive skin(see 
6.1.7). A subject must have a lactic acid stinging response COMBINEDscore of at least2
(combined from each timepoint assessment)to be considered to have sensitive skin and 
therefore be eligible to participate in the study. A trained technician will conduct the lactic 
acid Stinging Test on subjects to ascertain whether a subject has sensitive skin.
Eligible subjects will be randomizedand stratified, based on contact lens wearing status 
and skin type, to receive one of thetwofacial cleansing productsunder investigation and 
given instructions on how to correctly apply the product. Sufficient product will be 
provided so that the product can be used twice daily for the complete duration of study
period. 
The first use of the assigned test product will be performed at thestudy site, under study 
site staff supervision. One hour(±20minutes) after the first product application subjects 
will have further dermatologist and ophthalmological evaluations andthesubject self-
assessment questionswill beasked asecond time. Subjectswill receive a diary card to 
record twice daily product useover the duration of the study.Subjects will be instructed to 
use the test product twice daily at home during the study period of 21 (+2) days and will be 
instructed to contact the study siteif they have any reactions. 
At the end of the study period, final dermatological and ophthalmological assessmentswill 
be performed on all subjects. Subjects will also be asked the self-assessment questions 
based on their experience of product use.
Subjects will return theircompleted diary and all of theproduct packages, whether empty 
or not. The diary will be verified for adequate completion.
Assessments:
A qualified dermatologist and a qualified ophthalmologist will assess subjects at Visit 2 to 
determine eligibilityprior to any study product use, and 1hour (± 20minutes)following 
first supervised test product use. This is to ensure that the subject is free of any preexisting 
dermatological and ophthalmological pathology prior to using the study products (Edward, 
 
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2008).  Additionally, a final assessmentat Visit 3will be completed at the endof the 21 
(+2) day product use period. 
The intensity of any visual signs of cutaneous or ocular irritation will be recorded by the 
dermatologist and ophthalmologist, according to the severity of the reactions(Appendix 3
and 4). The dermatologist and ophthalmologist areresponsible forgrading the reactions, 
and their opinion on the classificationof the irritation scoresis final.
Female subjects with a Fitzpatrick phototype I to IV will be recruited to ensure any 
reactions are clearly visible on their skin.
Each subject’s medical history and medication history will be reviewed, as well as 
inclusion/exclusion criteria. Site staff will review lifestyle guidelinesand product directions 
with eligible subjects.
A dermatologist will characterizeeach subject’s skin and subjectswith dry or 
normal/combination skin type who are meet all other inclusion and exclusion will be 
included in the study.  Subjects with oily skin will be excluded from the study. 
Subjects will be asked to answer a series of self-assessment questions prior to any product 
application (Appendix 5).
Any skin irritation will be assessed by a dermatologist in the product application area and 
periocular area using the criteria recommended by the US Department of Health and 
Human Services Food and Drug Administration (FDA), 1999. The intensity of the reactions 
will be classified according to the scores obtained in the applied scale, according to
Appendix 3. 
Any ocular irritation will be assessed by anophthalmologist, through the observationof the 
presence of twofactors:Lacrimation Intensity and Conjunctiva Involvement, according to 
Appendix 4. Forthe initial pre-treatment assessment, the 1hour after the first application 
assessment, and for the finalday 21 (+2) dayassessment, each responsewill be graded as 
per theocularreaction intensity classification scale (Appendix 4). 
Application Quantity: 
The application quantity of the study products has been selected based on the assumption 
that, typically, 4mlof a cleansing product will be applied to a facial area of approximately 
400cm
2,as consistent with the average amount of non-lathering cleanser reported in the 
literature (Loretz, 2008).
 
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Both test products are the same formulation but are differentiated by the dispensing pack; 
to either amicellar cleanser or a foaming cleanser.
Micellar Cleanser instructions for use: Use morning and evening. Apply to a cotton pad and 
wipe over the entire face and closed eyes to gently cleanse. No need to rub or rinse. Cotton 
pads will be supplied.
Micellar Foaming Cleanser instructions for use: Use morning and evening.Massage gently 
onto wet skin on the face using fingertips, rinse thoroughly and pat skin dry.
4. SELECTION OF STUDY POPULATION AND WITHDRAWAL 
CRITERIA
Specific information regarding warnings, precautions, contraindications, adverse events, 
and other pertinent information on the GSK investigational product or other study treatment 
that may impact subject eligibility is provided in the Safety Statement.
Deviations from inclusion and exclusion criteria are not allowed because they can 
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 copyof the informed consent form. 
2. AGE
Aged between 18 and 65 years inclusive.
3. GENDER
Subject is female.
4. GENERAL HEALTH
Good general and mental health with, in the opinion of the investigator or medically 
qualified designee no clinically significant and relevant abnormalities in medical history or 
upon physical(dermatologist or ophthalmologist)examination.
 
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5. SKIN TYPE
a) Fitzpatrick phototype I to IV (see Appendix 1)–VISIT 2
b) Sensitive Skin (as determined by the lactic acid Stinging test)
c) Dermatologist score of zero (Appendix 2)-VISIT 2
d) Ophthalmologist score of zero(Appendix 3)-VISIT 2
e) Dermatologist assessed Dry or Normal/Combination Skin-VISIT 2
6. COMPLIANCE
Agreement to comply with the procedures and requirements of the study andto attend the 
scheduled assessmentvisits.
7. OTHER CRITERIA
Frequent use of facial cosmetic make-up, including eye-make-up (5 out of 7 days per 
week).
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 skinappearance 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. 
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 
 
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study.
d) Considered immune compromised. 
e) Participants with dermatographism.
f) Currently using any medication which in the opinion of the investigator, mayaffect 
the evaluation of the study product, or place the subject at undue risk
g) Use of the following topical or systemic medications: immunosuppressants,
antihistamines, non-hormonal anti-inflammatory drugs, and corticosteroids upto 2
weeks before screeningvisit and during the study.
h) Oral or topical treatment with vitamin A acid and/or its derivatives up to 1month 
before the screening visit and during the study.
i) Intention of being vaccinated during the study period or has been vaccinatedwithin 
3 weeks of the screening visit.
j) Currently receiving allergy injections, or received an allergy injection within 7days 
prior to Screening visit, or expects to begin injections during study participation
4. ALLERGY/ INTOLERANCE
a) Previous history of atopy with regards to allergic reactions, irritation or intense 
discomfort feelings to topical-use products, cosmetics or medication.
b) Known or suspected intolerance or hypersensitivity to the study materials (or
closely related compounds) or any of their stated ingredients
5. CLINICAL STUDY/ EXPERMENTAL PRODUCT
a) Participation in another clinical study (including cosmetic studies) or receipt of an 
investigational drug within 30 days 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.
 
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7. DIAGNOSTIC ASSESSMENTS AND OTHER CRITERIA
a) Any Subject who, in the judgment of the Investigator, should not participate in the 
study.
b) Any subject with corneal ulcers, keratoconus, blepharitis,meibomitis, pterygium, 
chemosis, moderately or severe hyperemia or other active oculardiseases.VISIT 2
c) Any skin marks on the facethat might interfere with the evaluation of possible skin 
reactions (e.g. pigmentation disorders, vascular malformations, scars, tattoos, 
excessive hair, numerous freckles).
d) Prisoner or involuntary incarcerated subject.
e) Subject from an indigenous tribe.
f) Subjects with a qualified dermatologist assessment of oily skin.VISIT 2
8. PERSONNEL
An employee of the sponsor or the study site or members of their immediate family.
4.3. Screening/ Baseline Failures
Screen failures are defined as subjects who consent to participate in the study but are never 
subsequently 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(SAEs). Re-
screening of subjects considered previous screen failures willnotbe allowed in this study
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 anAdverse Event (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, thecondition 
stabilizes, is otherwise explained, or the subject is lost to follow-up.
 
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The following actions must be taken in relation to a subject who fails to attend the clinic for 
a required study visit:
a) The site must attempt to contact the subject and re-schedule the missed visit as soon 
as possible. 
b) 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. 
c) 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. 
d) 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-randomization will notbe replaced.
4.6. Subject and Study Completion
A completed subject is one who has completed all phases of the study.The end of the study 
is defined as the date of the last subject’s last visit.
5. PRODUCT INFORMATION
5.1. Study Product
The following study products will be supplied by the Clinical Supplies Department, 
GSKCH:
Test Product 1
Test Product 2
Product Name
Micellar Cleanser
Micellar Foaming 
Cleanser
Product Formulation Code 
(MFC)
Product Format
200ml Clear plastic bottle
150ml Plastic pump pack
Application Quantity
To be used as per normal home use application
Route of Administration
Topical dermal application
Application Instructions
Use morning and evening. 
Apply to a cotton pad and 
wipe over the entire face 
Use morning and 
evening.
Massage gently onto wet 
 
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and closed eyes to gently 
cleanse. 
No need to rub or rinse. 
Cotton pads will be 
supplied. *
skin on the face using 
fingertips, rinse 
thoroughly and pat skin 
dry.
*Cotton padswill additionally be suppliedby the study site
Other items to be supplied by the clinical study site:
1. 10% Aqueous Lactic Acid solution –For lactic acid stinging test  
2. Saline solution –For lactic acid stinging test  
3. Cotton Buds -For lactic acid stinging test  
4. Cotton pads for use with micellar cleanser treatment arm
5.2. Application Schedule
Each eligible subject will receive one of the two cleansing productsunder investigation and 
given instructions on how to correctly apply the product. Sufficient product will be 
provided for the complete duration of the studyperiod. Subjectswill also receive a diary
card with their assigned product to be completed at hometo record each product use.
The first use of the assigned product will be performed at thestudy site, under study site 
staff supervisionand recorded on the provided diary card. Subjects will then be instructed 
to use their assigned product at home again that evening and continue to use at home twice 
daily during the study period of 21 (+2) daysper the instructionsof use, including the 
morning of their final visit, recording each use on the diarycard.
If subject is a contact lens wearer, contact lenses should be removed prior to any product 
application.
Subjects will return their completed diary and all of the product packages, whether empty 
or not. The diary will be verified for adequate completionand product use compliance.
As the usage of the productis indicated as twicedaily, for a minimum of 21days and a 
maximum of 23 days, a minimum of 42applications and a maximum of46applications 
will beexpected.
 
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5.3. Product Assignment
Subjects will be assigned toone of the two teststudy productsin accordance with the 
randomization schedule generated by an approved GSKCH vendor, prior to the start of the 
study, using validatedsoftware.
5.3.1Randomization
A unique screening number will identify each subject screened for studyparticipation. 
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 
randomized according to the randomization schedule, which will be prepared (stratified) to 
achieve balance between contact lens wearer (Yes or No) and cosmetic skin type (dry or 
normal/combination).
THERE WILL BE A TOTAL OF 4 STRATA:
CONTACTLENS WEARER + DRY SKIN
CONTACT LENS WEARER + NORMAL/COMBINATION SKIN
NON CONTACT LENS WEARER + DRY SKIN
NON CONTACT LENS WEARER + NORMAL/COMBINATION SKIN
Randomization numbers will be assigned in ascending numerical order as each subject is 
determined to be fully eligiblewithin each strata specific list.
The study site will receive two versions of the randomization schedule, each in a sealed 
envelope and clearly marked as either “For Dispensing”or “Emergency Use Only”. The 
“For Dispensing”schedule will contain the list of randomization numbers and the test 
product code, a letter code A, or B will be used to determine which product is to dispensed.
To maintain the blinding of the study as much as possible, all treatment allocations for all 
randomization numbers on thisrandomization schedule will be masked with scratch-off 
panels. Only the panels required for the emergency unblinding the particular subject should 
be removed
The ‘Emergency Use Only’randomization schedule will only be removed from the sealed 
envelope in an emergency situation. This schedule will have a randomization number 
 
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followed by the letter. The schedule will have a footnote with a key for the letters 
identifying the treatments.
5.3.2Blinding
The study statistician and other employees of the Sponsor who may influence study 
outcomes are blinded to the product allocation of subjects.
Site staffdispensing and carrying out the first supervised product application will be aware 
of each subject’s test product and must not divulge information to other study staff or the 
qualified dermatologist and/orqualified ophthalmologist who will be blinded to subject 
product assignment.
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 ml bottles and the 
micellar foaming cleanser ( 
 will be supplied in 150ml pump packs. Both 
products will have a study label affixed by the Sponsor to the outer packaging. Each study 
label will contain, but not be limited to, protocol number, productcode letter, directions for 
use and storagerequirements.
Both test products are the same formulation but are differentiated by the dispensing pack; 
to either a micellar cleanser or a foaming cleanser.
Care should be taken with the supplied products and their labels so that they are maintained 
in good condition.  It is important that all labels remain intact and legible for the duration of 
the study. Subjects should be instructed to not remove or deface any part of the study label.
 
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5.4.1. Accountability of Product
All products supplied are for 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 and will contain the following information:
a) The identification of the subject to whom the study product was dispensed.
b) The date(s) and quantity of the study product dispensed to the subject.
c) The date(s) and quantity of the study product returned by the subject (if applicable).
The inventory must be available for inspection by the study monitor during the study. At 
the end of the study, study product supplies will be verified by the monitor.  Study product 
supplies will then be either collected by the study monitor or returned bythe investigator or 
designee to the GSKCH Clinical Supplies Department or designated vendor, or destroyed 
by the study site upon GSK authorization,
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 sectionlists the procedures and parameters of each planned study assessment.  The 
exact timing of each assessment is listed in the Schedule of Events section.
Adherence to the study design requirements, including all assessments and procedures are 
essential andrequired 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.
 
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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 dated consent will be provided by the investigator or by 
GSKCH.  The investigator, or designee, should sign and date the consent form to confirm 
that the consent process was completed correctly after the subject has signed.  The subject 
willbe 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’swillingness 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 theInvestigator (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, gender and race.
6.1.4. Contact Lens Wearer Status Assessment
The following demographic parameter will be captured by the Investigator or designee and 
recorded on the CRF: Contact Lens Wearer (Yes/No).
6.1.5. Inclusion / Exclusion Criteria
Inclusion/exclusion criteria (excluding inclusion criteria 5A, 5c, 5d, and 5e and exclusion 
criteria 7Band 7f) will be assessed by the Investigator or designee and recorded on the 
CRF.
 
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6.1.6. Medical History and Concomitant Medication
Medical history will be assessed asrelated 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.
6.1.7.Lactic Acid Stinging Test
Subjectswill be instructed to wash their face with warm (room temperature) waterand dry 
it with papertowels.After 30 minutes the stinging test will be performed by a trained 
technician.
A 10% aqueous lactic acid solution (at room temperature) will be applied toone nasolabial 
foldand a saline solution (at room temperature) will be applied tothe othernasolabial fold. 
The location of the application will be randomised by the study site. The solutions will be 
applied by fully saturating a cotton bud, then using several sweeps of the saturated cotton 
bud along each of the nasolabial folds (Right and Left). 
At 2 minutes 30 seconds and 5 minutes after application, subjects will be asked to assess
their feelings of discomfort (Christensen et al., 1995), according to the following scale:
The reaction maytake 1 to 2 minutes to start, potentially intensifying up to5 minutes.The
test will be suspended after 5minutes, ifno local sensationis reported, or immediately after
subject assessment of severe intensity (score of 3). At this time or after 5minutes, the
subject will beinstructed to remove the solutionsby washing with water and to dry their 
face with a papertowel.
Subjects who report a combined score (i.e. sum of the 2 minute 30 seconds and 5 minute 
assessments) of greater than AT LEAST2 forthe lactic acid treated site compared to the 
saline solution treated site will be considered eligible for further participation in the study.
Any negative response will exclude the subject from further participation in the study.
 
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Any observed response that can be denoted according to the scoreof the reactions (per 
table above) will not be considered an adverse event. Only in the case of unusual reactions 
will these reactions and the consequences observed upon evaluation be documented as 
AE’s.
6.1.8. Subject Eligibility
Subject eligibility will be assessed by the Investigator or medically qualifieddesignee and 
recorded on the CRF.
6.2 Visit 2 –Baseline Visit
6.2.1. Inclusion / Exclusion Criteria
Inclusion criteria 5A, 5c, 5d, and 5e and Exclusion criteria 7Band 7f will beassessed by 
the Investigator or designee and recorded on the CRF. 
6.2.2. 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.
6.2.3. Fitzpatrick Skin Type Assessment
Fitzpatrick skin type assessment (Appendix 2)will be conducted by a trained evaluator and 
recorded on the CRF.
6.2.4.Skin Type Assessment 
A dermatologist will assess subjects skin type asdry,normal/combinationor oily and the 
classification will be recorded on the CRF.
6.2.5. Dermatologist Assessment
A qualified dermatologist will visually assess the subject at Visit 2to determine eligibility, 
prior to any study product use and 1hour (± 20 minutes)following first supervised test 
product use. This assures that the subject is free of any preexisting dermatological 
pathology prior to using the study products (Edward, 2008).  For inclusion into the study 
each subject should have a total cutaneous irritation score of zero at Visit 2 prior to any 
 
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product application. Additionally, a final assessment at Visit 3will be completed at the end 
of the 21 (+2) day product use period. 
The intensity of any visual signs of irritation will be recorded according to the grade of the 
reactions (Appendix 3) according to the skin dermal response (Table 1) and other features 
indicative of irritation (Table 2) observed. The dermatologist is responsible for grading the 
level of cutaneous irritation and their opinion on the correct classification of the irritation 
scores is final.
Any observed cutaneous responsethat can be denotedaccording to the grade of the 
reactions in Appendix 3 will not be considered an adverse event. Only in the case of 
unusual reactions will these reactions and the consequences observed upon evaluation be 
documented as AE’s.
6.2.6. Ophthalmologist Assessment
A qualified ophthalmologist will assess the subject at Visit 2to determine eligibility, prior 
to any study product use, and 1hour (± 20 minutes)following first supervised test product 
use. This assures that the subject is free of any preexisting ophthalmological pathology 
prior to using the study products. (Edward, 2008). For inclusion into the study each subject 
should have a total ocular irritation score of zero at Visit 2 prior to any product application. 
Additionally, a final assessment at Visit 3will be completed at the end of the 21 (+2) day 
product use period. 
Ocular irritation will be assessed through the observationof the presence of twofactors:
Lacrimation Intensity and Conjunctiva Involvement, according to Appendix 4. Forthe 
initial pre-treatment assessment, the 1 hour after the first application assessment, and for 
the finalday 21 (+2) dayassessment, each response will be graded as per theocular
reaction intensity classification scale (Appendix 4). The ophthalmologist is responsible for 
grading the reactions, their opinion on the classification of theocularirritation scores is 
final.
Any observed ocular response that can be denoted according to the grade of the reactions in 
Appendix 4 will not be considered an adverse event. Only in the case of unusual reactions 
will these reactions and the consequences observed upon evaluation be documented as 
AE’s.
6.2.7. Subject self-assessment
Subjects will be asked to answerthe self-assessment question as per Appendix 5 prior to 
any product use.
 
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The self-assessment questions will be asked again 1hour (± 20 minutes)following first 
supervised test product use. Additionally, a final assessment at Visit 3will be completed at 
the end of the 21 (+2) day product use period. 
6.2.8. Subject Eligibility
Subject eligibility for randomisation into the study will be assessed by the Investigator or 
medically qualified designee and recorded on the CRF.
6.2.9. Supervised Product Application
Each eligible subject will be randomised to a strata based on contact lens wearer status 
(Yes or No) and cosmetic skin type (dry or Normal/Combination) to receive one of the two 
cleansing productsunder investigation and given instructions on how to apply the product. 
Sufficient product will be provided so that the productcan be used for the complete study
period. 
The first use of the assigned product will be performed at thestudy site, under study site 
staff supervision.One hour(+20 minutes)after the first product application subjects will 
undergo further dermatologist (per section 6.2.5) and ophthalmologist(per section 6.2.6) 
assessmentsand be asked to respond to the subject self-assessment questions (Appendix 5).
If subject is a contact lens wearer, contact lenses should be removed prior to any product 
application.
Subjectswill receive a diary card with their assigned product to be completed at hometo 
record product use. Subjects will use the product at home, twice a day during the study 
period of21 (+2) days,and will be instructed to contact the study siteifthey have any 
reactions. 
6.3. Visit 3 -Last Subject Last Visit (LSLV) and Study Conclusion
Subjects will return to the study site after 21(+2) daysof twice daily product use. Subjects 
will return their test products and diary card. The diary card will be reviewed to check 
compliance and evaluate subject comments. The totalnumber of product applications and
total number of missed product applications will be recorded in the CRF.
Final dermatologist (per section 6.2.5) and ophthalmologist (per section 6.2.6) assessments 
will be completed and the subject will answer the self-assessment questions (Appendix 5) 
based on their experience of using the product.
 
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6.3.1. Diary Review
Any subject comment captured in the diary cardwhich isconsidered an adverse event will 
be reported as per the defined procedure in this protocol. Adverse event reporting 
procedures are summarised in Section 7. 
Subjects who apply the product more or less frequently than twice a day will be considered 
to have deviated from the protocol. Additional and missed applications will be recorded on 
the Deviations Log.
6.3.2. 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.
Adverse Event Definition:
a) An AE is any untoward medical occurrence in a patient or clinical investigation 
subject, temporally associated with the use of an investigational product(or the 
lactic acid stinging test procedure), whether or not considered related to the 
investigational product(or the lactic acid stinging test procedure).
b) NOTE: An AE can therefore be anyunfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of an investigational product(or the lactic acid stinging test 
 
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procedure).
Events meeting AE definition include:
a) 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.
b) Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.
c) New condition(s) detected or diagnosed after study product administration even 
though it may have been present prior to the start of the study.
d) Signs, symptoms, or the clinical sequelae of a suspected interaction.
e) 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:
a) 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. 
b) 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.
c) Medical or surgicalprocedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is an AE.
d) Situations where an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).
e) 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.
f) Any observed response that can be denoted according to the grade of the reactions 
for the Lactic Acid Stinging test. Only in the case of unusual reactions will these 
reactions and the consequences observed upon evaluation be documented as AE’s.
g) Any observed response that can be denoted according to the grade of the reactions 
 
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in Appendix 3 for cutaneous response and Appendix 4 for ocular response, will not 
be considered an adverse event. Only in the case of unusual reactions will these 
reactions and the consequences observed upon evaluation 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 
whichthe 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.
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
a) Medical or scientific judgment should be exercised in deciding whether 
reporting is appropriate in othersituations, 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.
b) Examples of such events are invasive or malignant cancers, intensive 
 
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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 andserious adverse events:
a) The investigator or site staff will be responsible for detecting, documenting and 
reporting events that meet the definition of an AE or SAE. 
b) The investigator or site staff will then record all relevant information regarding an 
AE/SAE in the CRF.
c) 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 medicalrecords prior to 
submission to GSK.
d) 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).
e) AEs will be collected following the conduct of the lactic acid stinging procedure 
and until 5days following last administration of the study product.
f) 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 provides consentto participate in the study up to and including any 
follow-up contact.  
g) 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 
 
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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:
a) The investigator is obligated to assess the relationship between study product and the 
occurrence of each AE/SAE.
b) 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.
c) The investigator will use clinical judgment to determine the relationship.
d) 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.
e) The investigator will also consult the Investigator Brochure (IB) and/or Product 
Information, for marketed products, in the determination of his/her assessment.
f) 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.
g) 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.
h) The investigator may change his/her opinion of causality in light of follow-up 
information, amending the SAE data collection tool accordingly.
 
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i) 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:
a) AEs will be recorded in the AE sectionof the CRF. 
b) Medical conditions recorded by the subject on a diary
 card or similar document that 
meet the definition of an AE must also be recorded in the AE section of the CRF, if 
not previously well-characterized by the investigator in the subject’s medical 
history. 
c) 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 symptoms or taken any medication 
(since your last visit) (today) (since your last dose) (since the last session)?”
d) The medically qualified investigator should review adverse events in a timely 
manner; this review should be documented in writing in the source document or in 
the CRF. 
e) After the study is completed at a given site, and the site has received their study data 
on Compact Discs (CDs), the electronic data collection tool will be removed from 
the internet to prevent the entry of new data or changes to existing data.
SAE Reporting to GSKCH:
A paper copy of the SAE form provided in the investigator study master file should be 
completed as fully as possible. 
It is essential to enter the following information: 
a) Protocol and subject identifiers
b) Subject’s demography
c) Description of events, with diagnosis if available
d) Investigator opinion of relationship to study product (see section 8.3)
e) Criterion for seriousness.
The following are desirable and are of particular relevance for investigator and GSKCH 
assessment of the SAE report:
a) Date of onset of AE 
b) Date AE stopped, if relevant
c) Study product start date
 
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d) Study product end date if relevant
e) Action taken on study product
f) 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.
FaxEMAIL Serious Adverse Events to:
Brazil Clinical Study Manager 
Telephone 
E-mail: 
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.
The initial report will be followed up with more information as relevant, or as requested by 
the GSKCH study manager.
7.5. Follow-up of Adverse Eventsand Serious Adverse Events
Follow-up of AEs and SAEs:
a) After the initial report, the investigator is required to proactively follow up with 
each subject and provide further information on the subject’s condition.
b) All AEs/SAEs will be followed until resolution, until the condition stabilizes, until 
the event is otherwise explained, or until the subject is lost tofollow-up.  
c) 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.
h) 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 relatedto the investigational product, or the conduct of the lactic acid 
stinging procedure, or study participation, the investigator will promptly notify 
GSKCH.
d) The investigator will submit any updated SAE data to GSK within the designated 
reporting time frames.
 
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PPD
PPD
PPD

Regulatory and ethics reporting requirements for SAEs:
a) 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.
b) GSKCH will comply with country specific regulatory requirements relating to 
safety reporting to the regulatory authority, IRBand investigators.
c) Investigator safety reports are prepared according to GSKCH policy and are 
forwarded to investigators as necessary.  An investigator safety report is prepared 
for a SAE(s) that is both attributable to investigational product and unexpected.  
The purpose of the report is to fulfill specific regulatory and GCP requirements, 
regarding the product under investigation.
d) An investigator who receives an investigator safety report describing a SAE(s) or 
other specific safety information (e.g., summary of listing of SAEs) from GSKCH 
will file it with the Investigator Brochure (or safety statement) and will notify the
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 investigational product. Information on pregnancy identified during 
the screening phase and prior to investigational productadministration does not need to be 
collected.
7.6.2. Action to be Taken ifPregnancy Occurs
Action to be Taken:
a) The investigator will collect pregnancy information on any subject who becomes 
pregnant while participating in the study after administration of the investigational 
product The investigator will record pregnancy information on the appropriateform 
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 
 
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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.
b) 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.
c) 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.
d) 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.
e) 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.
 
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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 the sponsor 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 accordancewith applicable GSKCH 
approved vendor 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.
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 approved vendor defined CRFs and transmitted 
electronically 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 a 
GSKCHapproved vendor. 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 quality and study performance. Any changes or corrections to data will 
be performed in the Electronic Data Capture (EDC) System, and it will include rationale 
for changes. The EDC system has an audit trail, which will provide a complete record of 
the changes and corrections endorsed by the Investigator.
 
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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
8.4. Processing Patient Reported Outcomes
Patient reported outcome (PRO) data are collected directly from the subject PRO measures 
e.g.diary cards, questionnaires etc., and entered into the sponsor’s clinical data 
management system (DMS) by the study site representative. In instances where the PRO 
data is entered into the DMS by GSKCH, the PROs will be anonymized, and forwarded to 
GSKCH for entry, as agreed and documented ahead of the study starting. PROs that are 
source will be retained by the investigator and certified copies will be sent to the GSKCH
approved vendor. 
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 on all PRO’s that 
will be forwarded to GSKCHor approved vendor.
9. STATISTICAL CONSIDERATIONS AND DATA ANALYSES
9.1 Sample Size Determination
A sufficient number of subjects will be screened (up to170) to randomize approximately 
92subjects (46per treatment group) toensure that at least 40subjectsin each treatment 
group completethe study(80 subjects in total). 
Randomization will be stratified by both contact lens wearer status (yes or no) and skin 
type (dry or normal/combination). The aim is to ensure balance of strata effects between 
treatment groups.
 
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The sample size is based on clinical considerations to provide descriptive information on 
the tolerability and safety of the products, and is consistent with ANVISA 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 randomized into the 
study and have at least one cutaneous or ocular assessment following study product 
application.
A separate Per Protocol (PP) analysis will not be performed. Protocol deviations will 
however be listed for review.
The Safety population includes all subjects from the point of the lactic acid stinging test 
procedure until completion of the study.
9.2.2. Exclusion of Data from Analysis
No data will be excluded from any analysis.
9.2.3. Criteria for Evaluationof Local Tolerance
The primary evaluation will be dermatologist and ophthalmologist visual assessments of 
local tolerance after 21 (+2)days of twice-daily study product applicationusing the ITT 
population.
This study will be considered a success if the majority (i.e. >50%) of subjects per treatment 
arm complete the study with combined dermatologist and ophthalmologist scores of zero at 
day 21 (+2). 
9.2.4. Criteria for Assessing Safety
Safety will be evaluated viaadverse events assessments using the Safety population.
9.2.5. 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.
 
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9.3. Statistical Methods and Analytical Plan
Additional details of the proposed statistical analysis will be documented in the statistical 
analysis plan (SAP), which will be written following finalization of the protocol and prior 
to study unblinding / analysis (as appropriate).
9.3.1. Demographic and Baseline Characteristics
Age will be summarized using descriptive statistics such as means, medians and standard 
deviations. Gender, race, Fitzpatrick skin type, contact leans wearer status and cosmetic 
facial skin type assessment by dermatologist will be summarized using frequency counts 
and percentages,
9.3.2. Primary Analysis(es)
The primary endpoints will be the dermatologist and ophthalmologist assessments of local 
tolerance through visual assessment of cutaneous (dermal response and superficial 
irritation) and ocular (conjunctiva involvement and lacrimal intensity) irritation 
scores/grades using the scales described in Appendix 2 and 3. 
Individual observations will be assessed based on these scales and a narrative description of 
all responses 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 response versus those without any response will be presented for each assessment at 
each time point for each of the study test products. If there are subjects with non-zero 
response scores, a combined skin (sum of dermal and superficial irritation) score, and a 
combined ocular (sum of conjunctiva and lacrimal) score at each time-point and for the 
sum across time points following test product application (sum of Baseline (Visit 2)and 
Visit 3) will be determined and summarised using descriptive statistics.
Data will also be presented by sub-groups, contact lens wearer status (yes, no) and skin 
type (dry, normal/combined)assessedat screening/baseline.
9.3.3. Secondary Analysis(es)
Thesecondary endpoints will be each subject self-assessment response (redness, dryness, 
burning, itching and stinging), as per Appendix 5.
 
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The secondary endpoints will be summarised as for the primary endpoints. Each subject 
assessment (redness, dryness, burning, itching and stinging, as per Appendix 5) and 
combined score (summed across these 5 assessments) will be presented at each time point 
and for the sum across time points following test product (sum of Baseline (Visit 2)and 
Visit 3) for each of the test products.
9.3.4. Safety Analysis(es)
Adverse events 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 presented for each of the test products.
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 enrollmentof 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), all 
applicable subject privacy requirements, and the guiding principles of the current version of 
the Declaration of Helsinki.  This includes, but is not limited to, the following:
1. Before initiating a trial, the investigator/institution should have written and dated 
approval/favorable opinion from the IRBfor the trial protocol (including 
amendments), written informed consent form, consent form updates, subject 
recruitment procedures (e.g., advertisements), investigator brochure/ safety 
statement (including any updates) and any other written information to be provided 
to subjects. A letter or certificate of approval will be sent by the investigator to the 
sponsor prior to initiation of the study, and also when subsequent amendments to 
the protocol are made.
 
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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, either verbally, in writing, or 
both.
10.3.Quality Control (Study Monitoring)
In accordance with applicable regulations including GCP, and GSK procedures, GSK or 
designee (i.e. third party vendor) monitors will contact the site prior to the start of the study 
to review with the site staff the protocol, study requirements, and their responsibilities to 
satisfy regulatory, ethical, and GSK requirements.
When reviewing data collection procedures, the discussion willinclude 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 theirtime 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.
 
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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.
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 at 
one or more or at all sites.  
If the trial is prematurely terminated or suspended for any reason, the investigator site 
should promptly inform thetrial 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 theIRB, and 
should provide the sponsor and theIRBa detailed written explanation of the 
termination or suspension.
2. If the GSKCH terminates or suspends a trial, the investigator should promptly 
inform theIRBand provide theIRBa 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.
 
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Where permitted by local laws/regulations or institutional policy, some or all of these 
records can be maintained in a format other than hard copy (e.g., microfiche, scanned, 
electronic); however, caution needs to be exercised before such action is taken. 
The investigator must ensure that all reproductions are legible and are a true and accurate 
copy of the original and meet accessibility and retrieval standards, including re-generating 
a hard copy, if required.  Furthermore, the investigator must ensure there is an acceptable 
back-up of these reproductions and that an acceptable quality control process exists for 
making these reproductions.
The investigator must assure that the subject’s anonymity 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 20years after completion or discontinuation of the study. The minimum 
retentiontime 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.
 
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GSK will also provide the investigator with the full summary of the study results.  The 
investigator isencouraged to share the summary results with the study subjects, as 
appropriate.
The procedures and timing for public disclosure of the results summary and for 
development of a manuscript for publication will be in accordance with GSK Policy.
A manuscriptwill be progressed for publication in the scientific literature if the results 
provide important scientific or medical knowledge.
 
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11. REFERENCES
ANVISA, Guideline for the Safety Evaluation of Cosmetics Products, 2012
ANVISA; Resolution 79/00, Annex XXIand its updates
Berardesca E, Farage M, Maibach H. Sensitive skin: an overview. Int J Cosmet Sci.
2013 Feb;35(1):2-8.
Birmingham, J. Clinical Aspects of Cutaneous Irritation and Sensitization, 
Toxicology and Applied Pharmacology 7:(54-59)
Christensen M, Klingman A M. An improved procedure for conducting lactic acid 
stinging tests on facial skin. J. Soc. Cosmetic. Chem. 1996; 47:1-11.
De Groot A C, White IR, Flyvholm L MA, Lensen G & Coenraads, PJ. 
Formaldehyde-releasers in cosmetics: relationship to formaldehyde contact allergy. 
Contact dermatitis 2010; 62:2-17
Dooms-Goossens A. Cosmetics as causes of allergic contact dermatitis. Cutis 1993; 
52: 316-320.
Edward, M. Jackson, and FMT Robillard Norman. "The controlled use test ina
cosmetic product safetysubstantiationprogram
."JournalofToxicology: Cutaneous 
and Ocular Toxicology1.2(1982):117-132
Farage, M. A., Katsarou, A. & Maibach, H. I. Sensory, clinical and physiological 
factors in sensitive skin: a review. Contact dermatitis 2006; 55:1-14.
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.
Food and Drug Administration. ICH Topic E6: Guideline for Good Clinical Practice.  
Fed Reg 1997; 62(90): 25691-709.
ICH Topic 6 Guideline for Good Clinical PracticeCPMP/ICH/135/95 17thJuly 1996.
Loretz LJ, Exposure data for cosmetic products: Facial cleanser, hair conditioner, and 
eye shadow. Food and Chemical Toxicology, 2008, 0278-6915, 46(5):1516
Lukacovic, Michael F., et al. "cleansing products." J. Soc. Cosmet. Chem 39 (1988): 
355-366.
Lumelsky V J, Shur M S & Wagner S. Sensitive skin. Sensors Journal, IEEE.
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12. APPENDICES
12.1. Appendix 1 -Abbreviations 
Abbreviations
AE
Adverse Event
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
g
Gram
GCP
Good Clinical Practice
GSK
GlaxoSmithKline
GSKCH
GlaxoSmithKline Consumer Healthcare
hr
Hour
ICF
Informed Consent Form
ICH
International Conference on Harmonization of Technical Requirements 
for Registration of Pharmaceuticals for Human Use
IEC
Independent Ethics Committee
ITT
Intention to Treat
LSLV
Last Subject Last Visit
m2
Square meter
MedDRA
Medical Dictionary for Regulatory Activities
mg
Milligram
min
Minute
ml
Milliliter
PII
Personally Identifiable Information
 
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PP
Per Protocol
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
 
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SIGNATURE PAGE 
 
  
 
Date 
Signed By
 
Justification 
 
 
 
Date 
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Justification 
 
 
 
Date 
Signed By
 
Justification 
 
 
 
Date 
Signed By
 
Justification 
 
 
 
Date 
Signed By
 
 
Justification 
 
 
 
Date 
Signed By
 
 
Justification 
 
 
25-May-2017 22:15:41
 
Approved
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Approved
25-May-2017 17:46:01
Clinical Operations Approval
Biostatistics Approval
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PPD
PPD
PPD
PPD