A Clinical Study to Assess the Local Cutaneous and Ocular Tolerance of Three Developmental Cosmetic Facial Skin Care Formulations in Healthy Females With Clinically Assessed Sensitive Skin.
Phase: NA
Conditions: Skin Care
Sponsor: GlaxoSmithKline

GSK Consumer Healthcare 
Clinical Protocol 
Protocol Number: 213059 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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CLINICAL PROTOCOL 
213059 
A Clinical Study to Assess the Local Cutaneous and Ocular 
Tolerance of Three Developmental Cosmetic Facial Skin 
Care Formulations in Healthy Females with Clinically 
Assessed Sensitive Skin. 
Protocol Number: 
213059 
Product Name: 
Developmental cosmetic facial serum,  
Developmental cosmetic facial lotion,  
Developmental cosmetic facial moisturizer 
United States (US) Investigational 
New Drug (IND) Number: 
N/A 
European Clinical Trials Database 
(EudraCT) Number: 
N/A 
Other Regulatory Agency Identified 
Number: 
N/A 
Phase: 
N/A 
213059 | Protocol Clinical Protocol 10 Mar 2020 | TMF-184333 | 1.0
This document contains confidentiality statements that are not relevant for this publicly
available version

GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 213059 
 
 
Property of GSK Consumer Healthcare - Confidential  
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Sponsor Information 
 
Sponsor Name & Legal 
Registered Address 
 
GlaxoSmithKline Consumer Healthcare 
(UK) Trading Limited 
980 Great West Road, 
Brentford, 
Middlesex, 
TW8 9GS, 
United Kingdom (UK) 
Sponsor Contact Details 
 
GlaxoSmithKline Consumer Healthcare 
(GSK CH) 
St George’s Avenue, 
Weybridge, 
Surrey, 
KT13 0DE, 
UK  
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Clinical Protocol 
 
 
Protocol Number: 213059 
 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SOP-208661 Clinical Protocol Template v5.0 
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Document History 
 
Document 
Version Summary of Changes  
Original protocol 
1.0 
Not applicable (N/A) 
Amendment 1 
 
 
Amendment 2 
 
 
 
 
 
Amendments incorporate all revisions to date, including amendments made at the request of 
country health authorities, institutional review boards/ethics committees (ECs), etc.   
 
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G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 1 3 0 5 9  
 
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H  
S O P -2 0 8 6 6 1 Cli nical Pr ot oc ol Te m plate v 5. 0  
Pa ge 4  of 5 6  
Pri n ci p al I n v e sti g at or Pr ot o c ol A gr e e m e nt P a g e  
 I c o nfir m a gree m e nt t o c o n d uct t he st u d y i n c o m plia nce wit h t he pr ot oc ol a n d a n y 
a me n d me nts acc or di n g t o t he c urre nt I nter n ati o nal C o nfere nce o n Har m o nisati o n G o o d 
Cli nical Practice (I C H G C P) g ui deli nes.  
 I ack n o wle d ge t hat I a m res p o nsi ble f or o verall st u d y c o n d u ct. I a gree t o p ers o nall y 
c o n d uct or s u per vise t he descri be d st u d y.  
 I a gree t o e ns ure t hat all ass ociates, c ollea g ues a n d e m pl o yees assisti n g i n t he c o n d uct of 
t he st u d y are i nf or m e d a b o ut t heir o bli gati o ns. Mec ha nis ms are i n place t o e ns ure site staff 
recei v es all a p pr o priate i nf or mati o n t hr o u g h o ut t h e st u d y. 
 I a gree t o c o n d uct t his st u d y i n f ull c o nf or ma nce wit h t he la ws a n d re g ul ati o ns of t he 
c o u ntr y i n w hic h t he researc h is c o n d u cte d a n d t he Declara ti o n of Helsi n ki. 
 
I n v esti gat or Na me: 
 
I n v esti gat or Q ualificati o ns: 
 
I n v esti gat or Si g nat ure: 
Date of Si g nat ure/ A gree me nt:  
D D -M m m -Y Y Y Y  
 
2 1 3 0 5 9 | Pr ot oc ol Cli nical Pr ot oc ol 1 0 Mar 2 0 2 0 | T M F- 1 8 4 3 3 3 | 1. 0
P P D

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Clinical Protocol 
 
 
Protocol Number: 213059 
 
 
Property of GSK Consumer Healthcare - Confidential  
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Table of Contents 
Sponsor Information ............................................................................................................ 2 
Document History ............................................................................................................... 3 
Principal Investigator Protocol Agreement Page ................................................................ 4 
Table of Contents ................................................................................................................ 5 
1 
PROTOCOL SUMMARY ................................................................................................ 10 
1.1 
Synopsis ................................................................................................................. 10 
1.2 
Schedule of Activities ............................................................................................ 13 
2 
INTRODUCTION ............................................................................................................. 14 
2.1 
Study Rationale ...................................................................................................... 14 
2.2 
Background ............................................................................................................ 14 
2.3 
Benefit/Risk Assessment ....................................................................................... 15 
2.4 
Mechanism of Action/Indication ........................................................................... 15 
3 
STUDY OBJECTIVES AND ENDPOINTS .................................................................... 15 
4 
STUDY DESIGN .............................................................................................................. 16 
4.1 
Overall Design ....................................................................................................... 16 
4.2 
Scientific Rationale for Study Design ................................................................... 17 
4.3 
Justification for Application .................................................................................. 18 
4.4 
End of Study Definition ......................................................................................... 18 
5 
STUDY POPULATION .................................................................................................... 18 
5.1 
Type and Planned Number of Subjects ................................................................. 18 
5.2 
Inclusion Criteria ................................................................................................... 19 
5.3 
Exclusion Criteria .................................................................................................. 20 
5.4 
Randomization Criteria .......................................................................................... 21 
5.5 
Lifestyle Considerations ........................................................................................ 21 
5.6 
Screen Failures ....................................................................................................... 22 
5.7 
Sponsor’s Qualified Medical Personnel ................................................................ 22 
5.8 
Clinical Assessor Qualifications ............................................................................ 23 
6 
INVESTIGATIONAL/STUDY PRODUCTS ................................................................... 23 
6.1 
Investigational/Study Product Supplies ................................................................. 23 
6.1.1 
Dosage Form and Packaging ................................................................. 24 
6.1.2 
Preparation and Dispensing ................................................................... 24 
6.2 
Administration ....................................................................................................... 25 
6.2.1 
Dosing Errors ........................................................................................ 25 
6.2.2 
Overdose ............................................................................................... 26 
6.3 
Investigational/Study Product Storage .................................................................. 26 
6.4 
Investigational/Study Product Accountability ....................................................... 26 
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6.4.1 
Destruction of Investigational/Study Product Supplies ........................ 27 
6.5 
Blinding and Allocation/Randomization ............................................................... 27 
6.6 
Breaking the Blind ................................................................................................. 28 
6.7 
Compliance ............................................................................................................ 28 
6.8 
Concomitant Medication/Treatment(s) .................................................................. 28 
7 
DISCONTINUATION OF STUDY INTERVENTION AND SUBJECT 
DISCONTINUATION/WITHDRAWAL ......................................................................... 29 
7.1 
Subject Discontinuation/Withdrawal ..................................................................... 29 
7.2 
Lost to Follow up ................................................................................................... 29 
8 
STUDY PROCEDURES ................................................................................................... 30 
8.1 
Visit 1 (Day -6 to 0) Screening .............................................................................. 30 
8.1.1 
Informed Consent .................................................................................. 30 
8.1.2 
Demographics ....................................................................................... 31 
8.1.3 
Medical History Current and Prior Medication/Treatment ................... 31 
8.1.4 
Inclusion/Exclusion Criteria.................................................................. 31 
8.1.5 
Lactic Acid Stinging Test (LAST) ........................................................ 31 
8.1.6 
Subject Eligibility.................................................................................. 33 
8.2 
Visit 2 (Day 1) Baseline/Randomization ............................................................... 33 
8.2.1 
Medical History and Prior Medication/Treatment ................................ 33 
8.2.2 
Subject self-assessment ......................................................................... 33 
8.2.3 
Dermatologist Assessment .................................................................... 33 
8.2.4 
Ophthalmologist Assessment ................................................................ 34 
8.2.5 
Supervised Product Application ............................................................ 34 
8.3 
Visit 3/Day 21 (Final Visit) ................................................................................... 35 
8.3.1 
Dermatologist Assessment .................................................................... 35 
8.3.2 
Ophthalmologist Assessment ................................................................ 35 
8.3.3 
Subject self-assessment ......................................................................... 36 
8.4 
Diary Review ......................................................................................................... 36 
8.5 
Study Conclusion ................................................................................................... 36 
8.6 
Follow-up Visit ...................................................................................................... 36 
9 
STUDY ASSESSMENTS ................................................................................................. 36 
9.1 
Screening Assessments .......................................................................................... 37 
9.2 
Safety and Other Assessments ............................................................................... 37 
9.2.1 
Dermatologist Assessment of Signs and Symptoms of Cutaneous 
Irritation ................................................................................................. 37 
9.2.2 
Ophthalmologist Assessment of Signs and Symptoms of Ocular 
Irritation ................................................................................................. 37 
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9.2.3 
Subject Self-Assessment of Signs and Symptoms of Cutaneous and 
Ocular Irritation ..................................................................................... 38 
9.2.4 
Pregnancy Testing ................................................................................. 38 
10 ADVERSE EVENT AND SERIOUS ADVERSE EVENTS ........................................... 38 
10.1 
Definition of an Adverse Event (AE) .................................................................... 38 
10.2 
Definition of a Serious Adverse Event (SAE) ....................................................... 40 
10.3 
Time Period and Frequency for Collecting AE and SAE Information .................. 41 
10.4 
Reporting Procedures ............................................................................................. 41 
10.4.1 
Reporting of an Adverse Event ............................................................. 42 
10.4.2 
Reporting of a Serious Adverse Event .................................................. 42 
10.5 
Evaluating Adverse Events .................................................................................... 43 
10.5.1 
Assessment of Intensity......................................................................... 43 
10.5.2 
Assessment of Causality ....................................................................... 43 
10.6 
Follow-up of AEs and SAEs .................................................................................. 44 
10.7 
Withdrawal Due to an Adverse Event ................................................................... 44 
10.8 
Regulatory Reporting Requirements for SAEs ...................................................... 45 
10.9 
Pregnancy .............................................................................................................. 45 
10.9.1 
Time Period for Collecting Pregnancy Information .............................. 45 
10.9.2 
Action to be Taken if Pregnancy Occurs .............................................. 45 
11 DATA MANAGEMENT .................................................................................................. 46 
11.1 
Case Report Form .................................................................................................. 46 
11.2 
Data Handling ........................................................................................................ 47 
11.2.1 
Data Queries .......................................................................................... 47 
11.3 
Processing Patient Reported Outcomes ................................................................. 47 
12 STATISTICAL CONSIDERATIONS AND DATA ANALYSES .................................. 48 
12.1 
Sample Size Determination ................................................................................... 48 
12.2 
Populations for Analysis ........................................................................................ 48 
12.3 
Statistical Analyses ................................................................................................ 48 
12.3.1 
Primary Analysis(es) ............................................................................. 48 
12.3.2 
Secondary Analysis(es) ......................................................................... 49 
12.3.3 
Safety Analysis(es) ................................................................................ 49 
12.3.4 
Other Analysis(es) ................................................................................. 49 
12.3.5 
Exclusion of Data from Analysis .......................................................... 49 
12.3.6 
Demographic and Baseline Characteristics ........................................... 49 
12.3.7 
Study Product Compliance and Use of Other Therapies ...................... 49 
12.3.8 
Handling of Dropouts and Missing Data .............................................. 50 
12.3.9 
Interim Analysis .................................................................................... 50 
13 STUDY GOVERNANCE CONSIDERATIONS .............................................................. 50 
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13.1 
Quality Control ...................................................................................................... 50 
13.2 
Quality Assurance .................................................................................................. 50 
13.3 
Regulatory and Ethical Considerations ................................................................. 51 
13.3.1 
Institutional Review Board/ Ethics Committee ..................................... 51 
13.3.2 
Ethical Conduct of the Study ................................................................ 51 
13.3.3 
Subject Information and Consent .......................................................... 51 
13.3.4 
Subject Recruitment .............................................................................. 52 
13.3.5 
Reporting of Safety Issues and Serious Breaches of the Protocol or 
ICH GCP ............................................................................................... 52 
13.4 
Posting of Information on Publicly Available Clinical Trial Registers ................. 52 
13.5 
Provision of Study Results to Investigators ........................................................... 52 
13.6 
Records Retention .................................................................................................. 53 
13.7 
Conditions for Terminating the Study ................................................................... 53 
14 REFERENCES .................................................................................................................. 54 
15 APPENDICIES .................................................................................................................. 55 
15.1 
APPENDIX 1 - ABBREVIATIONS ..................................................................... 55 
15.2 
APPENDIX 2 – FITZPATRICK SKIN TYPE GRADING .................................. 56 
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Clinical Protocol 
 
 
Protocol Number: 213059 
 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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List of in text tables 
Table 1-1 
Schedule of Activities ........................................................................... 13 
Table 3-1 
Study Objectives and Endpoints ........................................................... 15 
Table 6-1 
Investigational/Study Product Supplies ................................................ 23 
Table 8-1 
Lactic Acid Sting Test Score ................................................................. 32 
Table 9-1 
Dermatological Evaluation .................................................................... 37 
Table 9-2 
Ophthalmological Evaluation ................................................................ 37 
Table 9-3 
Subject Self-Assessment Scale for Signs and Symptoms of 
Cutaneous Irritation ............................................................................... 38 
Table 9-4 
Subject Self-Assessment Scale for Signs and Symptoms of Ocular 
Irritation ................................................................................................. 38 
Table 15-1 
Abbreviations ........................................................................................ 55 
Table 15-2 
FITZPATRICK SKIN TYPE GRADING ............................................ 56 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Clinical Protocol 
 
 
Protocol Number: 213059 
 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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1 
PROTOCOL SUMMARY  
1.1 
Synopsis 
Short Title:  
A clinical study to assess the local cutaneous and ocular tolerance of three developmental 
cosmetic facial skin care formulations. 
Background and Rationale: 
A cosmetic product that is freely available to the consumer must be safe when applied under 
normal or reasonably foreseeable conditions of use.  Thus, as a general requirement, the safety 
of a developmental formulation should be confirmed before it is marketed. 
Acceptability ‘in-use’ studies are useful clinical models which determine the irritation 
potential (local tolerance) of cosmetic formulations to provide confidence the finished 
products are suitable for general sale. 
The objective of this clinical study is to determine the local cutaneous and ocular tolerance of 
three developmental cosmetic facial skin care products (a serum, a lotion and a cream) in 
healthy females with clinically assessed sensitive facial skin, under normal conditions of use. 
Objectives and Endpoints: 
Objective(s) 
Endpoint(s) 
Primary 
To evaluate the local cutaneous tolerance 
profile (dermatologist assessed) of the 3 
investigational products in healthy females 
with sensitive facial skin under normal 
conditions of use after 21 days. 
Proportion of subjects determined by a 
dermatologist to have a clinically relevant 
positive outcome for cutaneous irritation after 
21 (+2) days of product use. 
Secondary 
To evaluate the local ocular tolerance profile 
(ophthalmologist assessed) of the 3 
investigational products in healthy females 
with sensitive facial skin under normal 
conditions of use after 21 days. 
Proportion of subjects determined by an 
ophthalmologist to have a clinically relevant 
positive outcome for ocular irritation after 21 
(+2) days of product use. 
To evaluate the local cutaneous tolerance 
profile (subject assessed) of the 3 
investigational products in healthy females 
with sensitive facial skin under normal 
conditions of use. 
Change from baseline (prior to any product 
application) in subject self-assessment 
scores of signs and symptoms of cutaneous 
irritation 1-2 hours after first product 
application.  
Change from baseline (prior to any product 
application) in subject self-assessment 
scores of signs and symptoms of cutaneous 
irritation after 21 (+2) days of product use. 
To evaluate the local ocular tolerance profile 
(subject assessed) of the 3 investigational 
products in healthy females with sensitive 
facial skin under normal conditions of use. 
Change from baseline (prior to any product 
application) in subject self-assessment 
scores of signs and symptoms of ocular 
irritation 1-2 hours after first product 
application. 
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Change from baseline (prior to any product 
application) in subject self-assessment 
scores of signs and symptoms of ocular 
irritation after 21 (+2) days of product use 
Safety 
To evaluate the general safety of the 3 
investigational products. 
Frequency and severity of Adverse Events. 
Study Design: 
This is a randomized, evaluator-blind (dermatologist and ophthalmologist), 3-arm, parallel-
group, single-center, clinical ‘in-use’ study to determine the local cutaneous and ocular 
tolerance of 3 developmental cosmetic facial skin care formulations (a serum, a lotion and a 
cream) in healthy female subjects aged 18 to 65 years (inclusive) with clinically evaluated 
sensitive facial skin, as determined by a positive response to a Lactic Acid Sting Test (LAST).  
A sufficient number of subjects will be screened (approximately 350) to randomize 
approximately 150 subjects to ensure that at least 135 subjects (45 per arm) complete the 
study.  
Subjects will be clinically assessed by a qualified dermatologist for a baseline clinical 
assessment of signs and symptoms of facial cutaneous irritation and by a qualified 
ophthalmologist for a baseline clinical assessment of the signs and symptoms of ocular 
irritation. Subjects will be asked to answer a series of self-assessment questions on the facial 
cutaneous and ocular signs and symptoms of tolerance prior to any product application. 
Site personnel involved in any clinical assessments will not be involved in the dispensing of 
test products and will be blind to product allocation. All reasonable efforts will be made to 
ensure the same assessors evaluate the same subject. Subjects will be required not to divulge 
the identity of the test products they have been using to any assessor, unless required for 
adverse event reporting or other medical or safety reason. 
For eligible subjects, the first application of their assigned product will be at the 
investigational site, under the supervision of a trained technician. Subjects will be asked to 
answer the same series of self-assessment questions again on the facial cutaneous and ocular 
signs and symptoms of tolerance 1-2 hours after first product application. 
Subjects will then be instructed to apply their assigned product at home again the same 
evening and twice-daily for a total of 21 (+2) days, as part of their normal skin care routine. A 
paper diary will be provided to each subject to record the number of daily applications of 
product, from first application at the study site to final application at home. The final 
application of product will be at home on the morning of the final visit (Visit 3). 
At the final visit (Visit 3), the dermatologist and ophthalmologist will conduct final clinical 
assessments of the signs and symptoms of cutaneous and ocular irritation, respectively. 
Subjects will also be asked to conduct final self-assessment of the signs and symptoms of 
facial cutaneous and ocular irritation. Subjects will return their completed diary and supplied 
product and will then be discharged from the study. 
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Study Products: 
Subjects will be assigned to 1 of the 3 study products in accordance with the randomization 
schedule. 
The investigational products are developmental formulations intended to be used as cosmetic 
facial skin care products (a serum, a lotion and a cream) by adult consumers with sensitive 
facial skin.  
The instructions for use provided to subjects in this study are consistent with those intended to 
be communicated to consumers when the product is made freely available for purchase. 
Type and Planned Number of Subjects: 
Healthy female subjects aged 18 to 65 years (inclusive) with clinically evaluated sensitive 
facial skin, as determined by a positive response to a LAST, with signs or symptoms of facial 
cutaneous irritation and no clinical signs or symptoms of ocular irritation will be enrolled into 
this study. Female subjects with sensitive facial skin have been selected as they have a greater 
familiarization and habitual use of facial skin care products. 
A sufficient number of subjects will be screened (approximately 350) to randomize 
approximately 150 subjects to ensure that at least 135 subjects (45 per arm) complete the 
study.  
The sample size for this study has been selected based on clinical considerations and to ensure 
compliance with the Agência Nacional de Vigilância Sanitária (ANVISA) Guideline for the 
Safety Evaluation of Cosmetic Products (ANVISA, 2012) which mandates an investigational 
product be tested on at least 30 subjects. 
Cosmetic manufacturers, even those with basic toxicologic testing and epidemiologic 
feedback on their products, are aware that l-10% of all cosmetic users note and often complain 
of discomfort, primarily on the face (Maibach and Engasser, 1988). Therefore, if 10% or less 
of subjects in each treatment arm experience a significant increase in clinical signs of 
irritation as determined to be clinically relevant by a dermatologist, the product will be 
considered to have comparable tolerability to other commercially available cosmetic skin care 
products. 
The focus of the statistical analysis will be the number of subjects determined by the 
dermatologist to have a clinically relevant positive outcome for cutaneous irritation, following 
21 (+2) days of twice-daily product use. With 45 subjects completing each treatment arm and 
under an assumption of 4% incidence of clinically evaluated intolerance, each group has a 
96.68% probability of observing less than 10% events in the study.  All the groups are 
independent hence the probability that all three groups individually result in less than 10% 
events is 0.96683, which equates to 0.9037, or a power of 90.4% that the study will result in 
all three groups having less than 10% of subjects with clinical intolerance. 
 
 
 
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1.2 
Schedule of Activities 
The schedule of activities table provides an overview of the subject visits and study 
procedures.   
The investigator may schedule visits (unplanned visits) in addition to those listed on the 
schedule of activities, to conduct evaluations or assessments required to protect the well-being 
of the subject. 
Table 1-1 
Schedule of Activities 
Procedure/Assessment 
Screening 
Randomization 
Final Visit 
Visit 1 
Day – 6 to 0 
Visit 2  
Baseline/Day 1a 
Visit 3 
Day 21 (+ 2) 
Informed Consent  
(date and time captured) 
X 
 
 
Demographics 
X 
 
 
Medical History 
X 
 
 
Medications Review 
(current/concomitant) 
X 
X 
X 
Inclusion/Exclusion Criteria 
X b 
X c 
 
Lactic Acid Sting Test (LAST) 
X 
 
 
Fitzpatrick Skin Type Assessment 
X 
 
 
Subject Eligibility for Enrolment 
X 
 
 
Clinical Assessment by Dermatologist 
 
X 
X 
Clinical Assessment by 
Ophthalmologist 
 
X 
X 
Subject Continued Eligibility 
 
X 
X 
Subject Self-Assessment 
 
X d 
X 
Randomization 
 
X 
 
Product and Diary Dispensing 
 
X 
 
Supervised Product Application 
 
X e 
 
Adverse Events (AEs) Review f 
X 
X 
X 
Product and Diary Return 
(Diary review) 
 
 
X 
Study Conclusion/Subject Exit from 
Study 
 
 
X 
Footnotes:  
a. Visit 1 and Visit 2 may be combined. If Visit 1 and Visit 2 are not combined, then Visit 2 must occur 
within 7 calendar days of Visit 1 
b. Inclusion criteria 1-5 and exclusion criteria 1-17 to be assessed at Visit 1 
c. Inclusion criteria 6-10 and exclusion criteria 18-23 to be assessed at Visit 2 (if visit 2 is not 
combined with visit 1) 
d. Subject self-assessment on Visit 2 will occur prior to randomization and product application 
(baseline) and 1-2 hours after first supervised product application  
e. If Visit 2 is combined with Visit 1, there should be a minimum of 30 minutes after the LAST has 
completed before the supervised product application. 
f. 
Adverse Events (AEs) and therefore all Serious Adverse Events (SAEs) will be collected 
immediately after a subject provides consent to participate in the study by completing the Informed 
Consent Form (ICF).
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2 
INTRODUCTION 
2.1 
Study Rationale 
GSK CH has developed 3 new cosmetic skin care formulations (a serum, a lotion and a 
cream) intended to be suitable for use by adult consumers with sensitive facial skin. Clinical 
data are required to demonstrate that the developmental formulations have favorable local 
tolerance profiles in the target population under normal conditions of use, prior to 
commercialization.  
Complete information for the developmental cosmetic facial serum, lotion and cream may be 
found in the single reference safety document (SRSD), which for this study is the Safety 
Statement. 
2.2 
Background 
In recent years the cosmetic industry has grown considerably, along with its concern for 
developing safe and effective products.  Heightened industry awareness, consumer and 
regulatory agency requirements have led cosmetic manufacturers to adopt procedures that 
provide a robust assessment of the risks and benefits of their products.  This includes the 
conduct of clinical tests to assess safety and efficacy, which are often coordinated by 
dermatologists or other experts before marketing a new product.  These procedures provide 
greater assurance of safety for cosmetic manufacturers, increasing their credibility and 
confidence among consumers. 
A cosmetic product that is freely available to the consumer must be safe when applied under 
normal or reasonably foreseeable conditions of use. Thus, as a general requirement, the safety 
of a developmental formulation should be confirmed before it is marketed (Guideline for the 
Safety Evaluation of Cosmetic Products; Agência Nacional de Vigilância Sanitária 
(ANVISA), 2012; Cosmetics Europe, 2004). 
Acceptability ‘in-use’ studies are useful clinical models to determine the irritation potential 
(local tolerance) of a cosmetic formulation to provide confidence an investigational product is 
suitable for general sale in the target population. Such studies aim to provide a clinical and 
subjective characterisation of the signs and symptoms of irritation following regular 
application of a topical product and often involve dermatologist and ophthalmologist 
oversight. 
Sensitive skin may be characterized by sensations including stinging, burning and itching, 
often without any visible signs or symptoms. The absence of visible signs or symptoms of 
irritation presents a challenge in the diagnosis of sensitive skin. However, several substances 
are known to trigger an irritant response in people with sensitive skin, such as benzoic acid, 
cinnamic acid, non-ionic emulsifiers, sodium lauryl sulfate, lactic acid, propylene glycol, urea 
and sorbic acid (De Groot et al, 2010; Lundov et al, 2010). Therefore, a routine test to 
diagnose sensitive skin is a lactic acid sting test (LAST), whereby an aqueous solution of 
lactic acid is applied to the facial nasolabial fold to try and trigger a sensorial response, often 
alongside a placebo such as saline. The stinging sensation response to the irritant may be 
measured in a binary way (i.e. presence or absence) or with a magnitude scale (Farage et al, 
2006). The LAST procedure allows for the characterization and enrollment of subjects with 
sensitive facial skin into clinical trials to enable the local tolerance of an investigational 
product to be investigated in this population.  
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2.3 
Benefit/Risk Assessment  
The 3 new cosmetic skin care formulations (a serum, a lotion and a cream) intended to be 
suitable for use by adult consumers with sensitive facial skin.  
Complete information for these formulations may be found in the single reference safety 
document (SRSD), which for this study is the Safety Statement.  
2.4 
Mechanism of Action/Indication 
Cosmetic products are preparations applied to the body, especially the face, intended to be 
applied for cleansing, beautifying, promoting attractiveness, or altering the appearance 
without affecting the body's structure or functions.  The investigational products in this study 
are cosmetic facial skin care products (a serum, a lotion and a cream) that are intended to be 
applied topically to the face by healthy female subjects with sensitive facial skin, immediately 
after cleansing, with the intent of delivering ingredients directly onto the skin. 
The European Union Cosmetics Directive defines a cosmetic as any substance or preparation 
intended to be placed in contact with the external parts of the human body with a view 
exclusively or mainly to cleaning, perfuming, changing appearance and/or correcting body 
odours and/or protecting or keeping in good condition (European Commission (EC), 2009). 
This is a consistent definition of cosmetic products per ANVISA (ANVISA, 2012) 
3 
STUDY OBJECTIVES AND ENDPOINTS 
Table 3-1 
Study Objectives and Endpoints 
Objective(s) 
Endpoint(s) 
Primary 
To evaluate the local cutaneous tolerance 
profile (dermatologist assessed) of the 3 
investigational products in healthy females 
with sensitive facial skin under normal 
conditions of use after 21 days. 
Proportion of subjects determined by a 
dermatologist to have a clinically relevant 
positive outcome for cutaneous irritation after 
21 (+2) days of product use. 
Secondary 
To evaluate the local ocular tolerance profile 
(ophthalmologist assessed) of the 3 
investigational products in healthy females 
with sensitive facial skin under normal 
conditions of use after 21 days. 
Proportion of subjects determined by an 
ophthalmologist to have a clinically relevant 
positive outcome for ocular irritation after 21 
(+2) days of product use. 
To evaluate the local cutaneous tolerance 
profile (subject assessed) of the 3 
investigational products in healthy females 
with sensitive facial skin under normal 
conditions of use. 
Change from baseline (prior to any product 
application) in subject self-assessment 
scores of signs and symptoms of cutaneous 
irritation 1-2 hours after first product 
application.  
Change from baseline (prior to any product 
application) in subject self-assessment 
scores of signs and symptoms of cutaneous 
irritation after 21 (+2) days of product use. 
To evaluate the local ocular tolerance profile 
(subject assessed) of the 3 investigational 
products in healthy females with sensitive 
facial skin under normal conditions of use. 
Change from baseline (prior to any product 
application) in subject self-assessment 
scores of signs and symptoms of ocular 
irritation 1-2 hours after first product 
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application. 
Change from baseline (prior to any product 
application) in subject self-assessment 
scores of signs and symptoms of ocular 
irritation after 21 (+2) days of product use 
Safety 
To evaluate the general safety of the 3 
investigational products. 
Frequency and severity of Adverse Events. 
The objective of this clinical study is to evaluate the local tolerance profile of 3 
developmental skin care products; a serum, a lotion and a cream, in healthy females with 
clinically assessed sensitive facial skin under normal conditions of use.  
Cosmetic manufacturers, even those with basic toxicologic testing and epidemiologic 
feedback on their products, are aware that l-10% of all cosmetic users note and often complain 
of discomfort, primarily on the face (Maibach and Engasser, 1988). Therefore, if 10% or less 
of subjects in each treatment arm experience a significant increase in clinical signs of 
irritation as determined by a dermatologist, the product will be considered to have comparable 
tolerability to other commercially available cosmetic skin care products. 
4 
STUDY DESIGN  
4.1 
Overall Design 
This is an evaluator-blind (dermatologist and ophthalmologist), randomized, 3-arm, parallel 
group, single-center, clinical ‘in-use’ study to determine the local cutaneous and ocular 
tolerance profiles of 3 developmental cosmetic facial skin care products in healthy female 
subjects aged 18 to 65 years (inclusive) with clinically-evaluated sensitive skin as determined 
by a positive response to a LAST (per Lactic Acid Stinging Test (LAST), with signs or 
symptoms of cutaneous irritation and no ophthalmological conditions. 
A sufficient number of subjects will be screened (approximately 350) to randomize 
approximately 150 subjects to ensure that at least 135 subjects (45 per arm) complete the 
study. It is deemed that 45 subjects per arm are considered sufficient to assess the primary 
endpoint: proportion of subjects determined (by a dermatologist) to have a clinically relevant 
positive outcome for cutaneous irritation after 21 days of product use. The sample size for this 
study has been selected based on clinical considerations and to ensure compliance with the 
ANVISA Guideline for the Safety Evaluation of Cosmetic Products (ANVISA, 2012) which 
mandates an investigational product be tested on at least 30 subjects. 
At Visit 1 (screening), subjects who agree to participate in the study by signing the informed 
consent form will be evaluated against the inclusion criteria 1-5 and exclusion criteria 1-17, 
and their medical history, prior and current medications and demographic information, 
including Fitzpatrick skin photo-type, will be recorded. Subjects will subsequently undergo a 
LAST in the nasolabial fold region to confirm whether they have sensitive facial skin. 
Subjects will only be considered eligible to continue in the study if they present a positive 
response to the LAST.  
At Visit 2 (randomization/baseline) a qualified dermatologist and a qualified ophthalmologist 
will assess each subject for baseline scoring of the clinical signs and symptoms of cutaneous 
and ocular irritation, respectively. Subjects will also be evaluated against inclusion criteria 6-
10 and exclusion criteria 18-23 and those subjects who continue to be eligible to participate in 
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the study will be instructed to self-assess the signs and symptoms of cutaneous and ocular 
irritation they are currently experiencing (baseline assessment) and will be randomized to one 
of the 3 study products. 
The first application of the assigned study product will be at the investigational site under the 
supervision of a trained technician. Subjects will be instructed self-assess the signs and 
symptoms of cutaneous and ocular irritation they are currently experiencing 1-2 hours after 
first product application. 
Visit 1 and Visit 2 may be combined. If Visit 1 and 2 are not combined, Visit 2 must occur 
within 7 calendar days of Visit 1. If Visits 1 and 2 are combined, the baseline dermatologist 
and ophthalmologist assessments and subject self-assessment of cutaneous and ocular 
irritation will occur before the LAST and any product application. The LAST will be 
completed at least 30 minutes prior to first product application. 
Subjects will be instructed to apply their assigned study product at home again the same 
evening of their first supervised application and then twice-daily for a total of 21 (+2) days as 
part of their normal skin care routine. A paper diary will be provided to each subject to record 
the number of daily applications of product, from first application at site to final application at 
home. Subjects may also record additional information such as AEs or medications used 
during the home use period in the provided diary.  
The final application of product will be at home on the morning of the final visit (Visit 3).   
At Visit 3 (final visit), the dermatologist and ophthalmologist will conduct final assessments 
of the signs and symptoms of cutaneous and ocular irritation, respectively.  
A total dermatologist score will be calculated as the sum of the erythema, dryness, scaling and 
edema scores for the baseline visit and final visit. The dermatologist will determine whether 
any subject with an increase in total dermatologist score at final visit versus baseline 
experienced a clinically relevant positive reaction, or not. Similarly, a total ophthalmologist 
score will be calculated as the sum of the eczema of the eyelid, conjunctivitis, follicles and 
chemosis conjunctivae scores for the baseline visit and final visit. The ophthalmologist will 
determine whether any subject with an increase in total ophthalmologist score at final visit 
versus baseline experienced a clinically relevant positive reaction, or not.  
Subjects will also be asked to provide final self-assessment of the signs and symptoms of 
cutaneous and ocular irritation they are currently experiencing for comparison versus baseline. 
Subjects will return their completed diary and study product and will be discharged from the 
study. 
4.2 
Scientific Rationale for Study Design 
Acceptability ‘in use’ studies aim to determine the irritation potential of topical products in 
the target population under the intended conditions of use, prior to commercialization. Per 
ANVISA guidelines, acceptability studies are indicated to be conducted for a 3-week period 
of use in a minimum of 30 subjects and should take into account the normal conditions of use. 
The investigational products being evaluated are developmental formulations intended to be 
used as cosmetic facial skin care products (a serum, a lotion and a cream) by adult consumers 
with sensitive facial skin. The formulations have been designed to provide topical 
moisturization while minimizing the quantity of known irritants and allergens.  
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Subjects will only be considered eligible to enter the study if they have a dermatologist signs 
and symptoms cutaneous irritation score of 0.5 (very slight) or greater for erythema and 
dryness and a score of 0 (none) or 0.5 (very slight) for scaling and edema, as this is 
representative of the target consumer for the finished product. Subjects presenting with a 
score of 1 (slight) or greater for edema are excluded from the study as this condition is not 
reflective of the target population.  
Any subject presenting with a score of 3 (severe) in any cutaneous irritation attribute will not 
be eligible to participate in the study, as this condition does not reflect the target population 
for the product.  
4.3 
Justification for Application 
Subjects will be instructed to use their assigned study product twice-daily (morning and 
evening) as part of their normal facial skincare regimen, post cleansing and before or in place 
of moisturization (as appropriate for the assigned product), in their usual manner.  
The instructions for use provided to subjects in this study are consistent with those intended to 
be communicated to consumer when the product is made freely available for purchase.  
Subjects who already use a facial serum, lotion or moisturizer will be instructed to replace 
their current product with the product they have been assigned to use for the duration of the 
study. 
The application quantity of the study products is not specifically detailed in line with typical 
‘in use’ clinical study designs, where the intent is to model real-world conditions in which 
consumers tend to self-calibrate application amounts depending on the needs of their own skin 
and their aesthetic preferences on a day to day basis.  
Subjects will be reminded that, as with all skin care products when topically applied to the 
face, care should be taken to avoid getting the products into the eyes. If contact does occur, 
then subjects will be instructed to rinse the eyes thoroughly with water 
4.4 
End of Study Definition 
A subject will be considered to have completed the study if they complete all phases of the 
study including the last visit, or the last scheduled procedure shown in the Schedule of 
Activities. 
The end of this study is defined as the date of the last subject’s last visit (Visit 3). 
5 
STUDY POPULATION 
5.1 
Type and Planned Number of Subjects 
Healthy female subjects aged 18 to 65 years (inclusive) with clinically evaluated sensitive 
facial skin, as determined by a positive response to a LAST, with signs or symptoms of 
cutaneous irritation and no signs or symptoms of ocular irritation conditions will be enrolled 
into this study. Female subjects with sensitive facial skin have been selected as they have a 
greater familiarization and habitual use of facial skin care products. Males are not included, 
due to the potential of mechanical facial hair removal methods causing cutaneous irritation 
and confounding dermatologist visual assessments.  
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A sufficient number of subjects will be screened (approximately 350) to randomize 
approximately 150 subjects to ensure that at least 135 subjects (45 per arm) complete the 
study. Dropouts after randomization will not be replaced.  
An enrolled subject is one who has agreed to participate in the clinical study following 
completion of the informed consent process directly or via their legally authorized 
representative and successfully met eligibility criteria to proceed beyond the screening visit.  
This study can fulfill its objectives only if appropriate subjects are enrolled.  The following 
eligibility criteria are designed to select subjects for whom participation in the study is 
considered appropriate.  All relevant medical and non-medical conditions should be taken into 
consideration when deciding whether a subject is suitable for this protocol.   
Subject eligibility to participate in the clinical study should be reviewed and documented by 
an appropriate member of the investigator’s study team before subjects are included in the 
study. 
Site personnel performing and reviewing the subject inclusion and exclusion criteria and 
subject eligibility should be the investigator, a suitable Medically Qualified Person (MQP) or 
designee as appropriate. This should be documented in the site logs. 
5.2 
Inclusion Criteria 
An individual must meet all the following inclusion criteria to be eligible for enrollment into 
the study: 
1. Subject provision of a signed and dated informed consent document indicating that the 
subject has been informed of all pertinent aspects of the study before any assessment is 
performed. 
2. Subject is female who, at the time of screening, is between the ages of 18 and 65 years, 
inclusive. 
3. A subject who is willing and able to comply with scheduled visits, the application 
schedule, the lifestyle guidelines, and other study procedures. 
4. A subject in good general and mental health with, in the opinion of the investigator or 
medically qualified designee (if the investigator is not suitably qualified), no clinically 
significant/relevant abnormalities in medical history or upon dermatologist and 
ophthalmologist examination, or condition, that would impact the subject’s safety, 
wellbeing or the outcome of the study, if they were to participate in the study, or affect the 
individual’s ability to understand and follow study procedures and requirements. 
5. Subjects with sensitive facial skin, defined as a positive response to a LAST in the 
nasolabial area. 
6. A subject with a dermatologist signs and symptoms of cutaneous irritation score of 0.5 
(very slight) or greater for erythema. Per Table 9-1 Dermatological Evaluation 
7. A subject with a dermatologist signs and symptoms of cutaneous irritation score of 0.5 
(very slight) or greater for dryness. Per Table 9-1 Dermatological Evaluation 
8. A subject with a dermatologist signs and symptoms of cutaneous irritation score of 0 
(none) or 0.5 (very sight) for scaling. Per Table 9-1 Dermatological Evaluation  
9. A subject with a dermatologist signs and symptoms of cutaneous irritation score of 0 
(none) or 0.5 (very sight) for edema. Per Table 9-1 Dermatological Evaluation 
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10. A subject with an ophthalmologist total signs and symptoms of ocular irritation score of 
zero (0). Per Table 9-2 Ophthalmological Evaluation 
5.3 
Exclusion Criteria 
An individual who meets any of the following exclusion criteria will not be eligible for 
enrollment into the study: 
1. A subject who is an employee of the investigational site, either directly involved in the 
conduct of the study or a member of their immediate family; or an employee of the 
investigational site otherwise supervised by the investigator; or, a GSK CH employee 
directly involved in the conduct of the study or a member of their immediate family. 
2. A subject who has participated in other studies (including non-medicinal studies) 
involving investigational product(s) within 30 days prior to study entry and/or during 
study participation. 
3. A subject who is pregnant (self-reported) or intends to become pregnant during the study 
duration. 
4. A subject who is breastfeeding. 
5. A subject with known or suspected intolerance or hypersensitivity to the study materials 
(or closely related compounds) or any of their stated ingredients. 
6. A subject unwilling or unable to comply with the protocol Lifestyle Considerations 
required by this study, as described in this protocol. 
7. A subject with current or recent (within last 6 months before the start of the study) history 
of atopic lesions and/or eczema 
8. A subject with a history of allergic reactions to topical-use products, cosmetics or 
medications or their ingredients. 
9. A subject with any history of significant diseases or medical conditions known to alter 
skin or eye appearance or physiologic response (e.g. diabetes) which could, in the opinion 
of the Investigator, preclude topical application of the investigational products and/or 
interfere with the evaluation of the test site reaction. 
10. A subject presenting open sores, pimples, or cysts at the application site (face). 
11. A subject considered immune-compromised. 
12. A subject who has used any of the following topical or systemic medications up to two 
weeks before the screening visit: immuno-suppressants, antihistamines, non-steroidal anti-
inflammatory drugs (NSAIDS), and/or corticosteroids. 
13. A subject who has used oral or topical treatment with vitamin A acid and/or its derivatives 
up to 1 month before the screening visit. 
14. A subject who has been vaccinated up to 1 month before the screening visit or who is 
intending to receive a vaccination during their participation in the study. 
15. A subject with a recent history (within the last 5 years) of alcohol or other substance 
abuse. 
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16. A subject with any skin marks on the face that might interfere with the evaluation of 
possible skin reactions (e.g. pigmentation disorders, vascular malformations, scars, 
tattoos, excessive hair, numerous freckles). 
17. A subject who has previously been enrolled in this study. 
18. A subject with, in the opinion of the investigator or medically qualified designee, an acute 
or chronic medical or psychiatric condition that may increase the risk associated with 
study participation or investigational product administration or may interfere with the 
interpretation of study results and, in the judgment of the investigator or medically 
qualified designee, would make the subject inappropriate for entry into this study. 
19. Subjects with corneal ulcers, keratoconus, blepharitis, meibomitis, pterygium, chemosis, 
moderately or severe hyperaemia or other active ocular diseases. 
20. A subject currently using any medication which in the opinion of the investigator 
(medically qualified designee) may affect the evaluation of the investigational product or 
place the subject at undue risk. 
21. A subject with an active dermatosis (local or disseminated) that might interfere with the 
results of the study. 
22. A subject with a dermatologist signs and symptoms of cutaneous irritation score of 3 
(severe) for edema, scaling, erythema, or dryness. Per Table 9-1 Dermatological 
Evaluation 
23. A subject who, in the opinion of the investigator or medically qualified designee, should 
not participate in the study. 
5.4 
Randomization Criteria 
All subjects will be centrally randomized to one of the 3 study arms using an Interactive 
Response Technology (IRT), provided by the Sponsor. Subjects will be randomized into the 
study provided they have satisfied all subject selection criteria.  
The Sponsor will provide an additional randomization schedule for the LAST for the left and 
right side of the nasolabial fold, to ensure a balanced randomization of the two solutions 
(lactic acid and saline solution) for the screened subjects (per Lactic Acid Stinging Test 
(LAST).  
5.5 
Lifestyle Considerations 
Following consent to participate in the study by completing the ICF, subjects may be asked to 
remove any facial cosmetics (including moisturizers and make-up) prior to the visit 
assessments, using warm tap water and paper towels provided at the study site. 
Throughout the study subjects will continue to cleanse their face per their normal routine with 
their normal facial products. Subjects should continue with their normal facial skin care 
routine with the exception of replacing their current serum, lotion or cream with the product 
that they have been assigned to use for the duration of the study.  
If Visit 2 is combined with Visit 1, subjects maybe asked to remove any topical products 
(including cosmetics) from their face with warm tap warm and dry with paper towel at the 
study site. 
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During the entire study (Screening – Last Subjects Last Visit (LSLV)) the following must be 
avoided: 
 Making a change to current facial care habits and practices, including the addition or 
removal of any new facial topical product to their current regimen and/or switching brands 
of facial topical products. 
 Introduction of new home care products which may come into contact with the skin, 
including laundry detergent, shower gel, shampoo, bath soap. 
 Intentional exposure to artificial ultraviolet (UV) light or sunbathing. 
 Undergoing any non-invasive, minimally-invasive or invasive cosmetic or surgical 
procedures on the face, e.g. waxing, bleaching etc.  
 Consuming caffeinated drinks (e.g. coffee, tea, cola etc.) 2 hours prior to Visit 2. 
Visit 3: 
 Prior to the final visit (Visit 3), subjects must not apply any topical products (including 
cosmetics) to their face other than their assigned product.  
 Subjects must cleanse their face with either tap water or their current cleanser in the 
morning prior to site visit and apply their assigned product for the final use, 2-4 hours 
prior to the final visit. 
 Subjects must refrain from drinking caffeinated drinks (e.g. coffee, tea, cola etc.) 2 hours 
prior to the final visit. 
5.6 
Screen Failures 
Screen failures are defined as subjects who consent to participate in the clinical study but are 
not subsequently randomized. To ensure transparent reporting of screen failure subjects, a 
minimal set of screen failure information will include demography, screen failure details (e.g. 
withdrawal of consent), eligibility criteria, and any adverse events as applicable.  
Individuals who do not meet the criteria for participation in this study (screen failure) will not 
be re-screened. 
5.7 
Sponsor’s Qualified Medical Personnel 
Contact information for the sponsor's appropriately qualified medical personnel for the study 
is documented in the Study Contact List located in the investigator study master file held at 
the study site. 
The contact number is only to be used by investigational staff seeking advice on medical 
questions or problems in the event that the established communication pathways between the 
investigational site and the study team are not available.   
The contact number is not intended for direct use by study subjects.  To facilitate access to 
appropriately qualified medical personnel on study-related medical questions or problems, 
subjects will be provided with a contact card.  The contact card will provide, as a minimum, 
protocol identifiers, the subject’s study identification number, contact information for the 
investigational site, and contact details in the event that the investigational site cannot be 
reached to provide advice on a medical question or problem identified by a healthcare 
professional other than the investigator.   
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G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 1 3 0 5 9  
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H  
S O P -2 0 8 6 6 1 Cli nical Pr ot oc ol Te m plate v 5. 0  
Pa ge 2 3  of 5 6  
5. 8  
Cli ni c al A s s e s s or Q u alifi c ati o n s  
W here e ver p ossi ble all cli nical assess me nts will be ma de b y a  si n gle q ualifie d der mat ol o gist 
a n d a si n gle q u alifie d o p ht hal m ol o gist f or all s u bj ects t hr o u g h o ut t he st u d y. Eac h assess or will 
vis uall y e val uate s u bjects f or eli gi bilit y t o e nter a n d c o nti n ue i n t he trial at t he start ( Visit 1 or 
Visit 2 if n ot c o m bi ne d) a n d  at t he e n d of t h e 2 1 ( + 2) da y pr o d u ct use peri o d ( Visit 3).  
T he i nte nsit y of a n y vis u al si g ns of der mal irritati o n will be rec or de d acc or di n g t o t he gra de of 
t he reacti o ns i n t he 
D er mat ol o gi cal E val u ati o n (Safet y a n d 
Ot her 
Assess me nts ). T he 
der mat ol o gist is res p o nsi ble f or gra di n g t h e le vel of c uta ne o us irritati o n a n d t heir o pi ni o n o n 
t he c orrect cl assifi cati o n of t he irritati o n sc ores is fi nal. E ver y eff ort will be ma de t o e ns ure 
t he sa me der m at ol o gist will be use d t o e val uate all s u bjects i n t he st u d y.  
T he i nte nsit y of a n y vis u al si g ns of oc ular irritati o n will be rec or de d acc or di n g t o t he gra d e o f 
t he reacti o ns i n t he O p ht hal m ol o gical E val u ati o n (Safet y a n d Ot h er Assess me nts ). T he 
o p ht hal m ol o gist is res p o nsi ble f or gra di n g t he reacti o ns, t heir o pi ni o n o n t he classificati o n of 
t he oc ular irritati o n s c ores is fi nal. E ver y eff ort 
will b e 
ma de t o e ns ure t he s a me 
o p ht hal m ol o gist will be use d t o e val uate all s u bjects i n t he st u d y.  
A n y o bser ve d c uta n e o us or oc ular res p o nse t hat ca n be c o m pletel y descri be d b y  t he 
der mat ol o gist or o p ht hal m ol o gist gra d i n g s cales will n ot be c o nsi dere d a n a d verse e ve nt. O nl y 
i n t he cas e of u n us ual reacti o ns, i n t he o pi ni o n of t he cli nical e x pert, will t hese reacti o ns a n d 
t he c o nse q ue n ces o bser ve d u p o n e val uati o n be d oc u me nte d as A Es. 
6  
I N V E S TI G A TI O N A L/ S T U D Y P R O D U C T S 
F or t he p ur p oses of t his s t u d y, per I nter nati o nal C o nfere n ce o n Har m o nizati o n (I C H) 
g ui deli nes, a n d 
G S K p olic y, 
st u d y i nter ve nti o n is 
defi ne d as an y 
i n vesti gati o nal 
i nter ve nti o n(s), 
mar ket e d pr o d uct(s), place b o, or 
me dical de vice(s) i nte n de d t o be 
a d mi nistere d t o a st u d y p artici pa n t acc or di n g t o t he st u d y pr ot o c ol. 
6. 1  
I n v e sti g ati o n al/ St u d y Pr o d u ct S u p pli e s 
T he f oll o wi n g st u d y pr o d ucts will be s u p plie d b y t he Cli nical S u p plies De part me nt, G S K C H:  
T a bl e 6 -1  
I n v e sti g ati o n al/ St u d y Pr o d u ct S u p pli e s 
 
 
I n v e sti g ati o n al 
Pr o d u ct  1  
I n v e sti g ati o n al 
Pr o d u ct  2  
I n v e sti g ati o n al 
Pr o d u ct  3  
Pr o d u ct N a m e  
D e v el o p m e nt al S er u m  
D e v el o p m e nt al L oti o n  
D e v el o p m e nt al 
Cr e a m  
Pr o d u ct F or m ul ati o n 
C o d e ( M F C)  
 
 
 
Pr o d u ct F or m at  
4 0 m L p u m p p a c k  
5 0 m L t u b e  
5 0 m L t u b e  
Di s p e n si n g D et ail s  
A kit will b e di s p e n s e d t o e a c h s u bj e ct c o nt ai ni n g 2 b ottl e s/t u b e s  
A p pli c ati o n Q u a ntit y  
T o b e u s e d a s p er n or m al h o m e u s e a p pli c ati o n i n pl a c e of t h e c urr e nt 
f a ci al s ki n c ar e pr o d u ct.  
R o ut e of A d mi ni str ati o n  
T o pi c al d er m al (f a ci al) a p pli c ati o n  
A p pli c ati o n I n str u cti o n s  
A p pl y t wi c e d ail y t o 
fr e s hl y cl e a n s e d s ki n, 
c o nti n u e wit h y o ur 
n or m al m oi st uri si n g 
A p pl y t wi c e d ail y t o 
fr e s hl y cl e a n s e d s ki n. 
 
A p pl y t wi c e d ail y t o 
fr e s hl y cl e a n s e d 
s ki n . 
 
2 1 3 0 5 9 | Pr ot oc ol Cli nical Pr ot oc ol 1 0 Mar 2 0 2 0 | T M F- 1 8 4 3 3 3 | 1. 0
C CI
C CI
C CI

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Protocol Number: 213059  
 
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routine. 
Return Requirements 
All used/unused samples to be returned to the study site 
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. 
Opaque bags will be supplied by the Clinical Supplies Department, GSKCH for dispensing of 
the kits to subjects. 
Other items to be supplied by the clinical investigational site: 
 Aqueous Lactic Acid solution (10%) – For LAST  
 Saline solution (0.9 Molar) – For LAST  
 Cotton tipped swabs - For LAST  
 Paper towels 
Supplies provided by the clinical investigational site must also be stored in compliance with 
the label requirements in a secure place with limited or controlled access. 
Detailed instructions for the return of study product/study supplies for the accountability 
checks and subsequent destruction which will be provided by GSK CH during the study in 
time for study close out visit. 
6.1.1 
Dosage Form and Packaging 
The 3 developmental products (serum, lotion and cream) will be supplied to the clinical site as 
labelled packaged pump packs or tubes in a kit for dispensing by the site staff.  
The content of the product labels will be in accordance with all applicable regulatory 
requirements and will be the responsibility of the GSK CH Global Clinical Supplies group. 
Each study label will contain, but not be limited to, protocol number, container number, 
directions for use and storage requirements.  
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. 
All products supplied are for use only in this clinical study and should not be used for any 
other purpose. 
6.1.2 
Preparation and Dispensing  
The 3 developmental products (serum, lotion and cream) will be dispensed by suitable trained 
unblinded site personnel according to the randomization schedule provided.  
These staff members will not be involved in any safety, efficacy assessments or other aspects 
of the study that could be influenced by the knowledge of product a subject has been assigned 
to use. An additional member of site staff should ensure the dispensing procedures are 
completed accurately. 
Subjects will be centrally randomized to one of the 3 study arms using an Interactive 
Response Technology (IRT) in accordance with the randomization schedule generated by an 
approved GSK CH vendor, prior to the start of the study, using validated software. 
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6.2 
Administration 
Only subjects enrolled in the study may receive study products and only authorized site staff 
may supply study products. All study interventions must be stored in a secure, 
environmentally controlled, and monitored (manual or automated) area in accordance with the 
labeled storage conditions with access limited to the authorized site staff only. 
The first application of the assigned product will be conducted by the subject under the 
supervision of a trained technician at the study site at Visit 2 (Baseline) following completion 
of the baseline dermatologist and ophthalmologist assessments and subject self-assessment 
questions. 
If Visit 1 and Visit 2 are combined, first application of the assigned product will be conducted 
by the subject under the supervision of a trained technician at the site following completion 
of the baseline dermatologist and ophthalmologist assessments and subject self-assessment 
questions. There should be a minimum of 30 minutes after the LAST has completed before 
the baseline product application. 
Subjects will be instructed to self-administer their assigned product per the usage instructions 
the same evening of the visit and continue to use for a total of 21 days (+2 days). 
6.2.1 
Dosing Errors 
Dosing errors may result, in this study, from the administration of:  
 the wrong product, 
 at the wrong amount, 
 by the wrong subject,  
 at the wrong time,  
Such dosing errors occurring to a study subject are to be captured in the CRF.   
Dosing errors are reportable irrespective of the presence of an associated AE, including: 
 Dosing errors involving subject exposure to any of the study products; 
 Potential dosing errors or uses outside of what is foreseen in the protocol that do or 
do not involve the participating subject. 
If a dosing error is accompanied by an AE, as determined by the investigator, the dosing error 
and, any associated adverse event(s) are to be captured in the CRF AE form.  
Such medication/dosing errors occurring to a study subject are to be captured in the CRF.  In 
the event of medication dosing error, the sponsor should be notified immediately and under 
no circumstance should this exceed 24 hours. 
Dosing errors are reportable irrespective of the presence of an associated AE, including: 
 Medication/dosing errors involving subject exposure to any of the study products; 
 Potential medication/dosing errors or uses outside of what is foreseen in the 
protocol that do or do not involve the participating subject. 
If a dosing error is accompanied by an AE, as determined by the investigator, the dosing error 
and, any associated adverse event(s) are to be captured in the CRF AE form.  
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6.2.2 
Overdose 
An overdose is a deliberate or inadvertent administration of a product at an amount higher 
than specified in the protocol. 
Overdose is not likely to occur in this study. 
Limited quantities of the study product(s) will be supplied, and closely monitored by the site 
for each subject. 
Overdose per se is not an AE. However, any clinical sequelae of an overdose should be 
reported as an AE (and serious adverse event (SAE), if appropriate). For reporting, follow the 
AE and SAE reporting instructions. 
6.3 
Investigational/Study Product Storage  
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study products received and any discrepancies are reported 
and resolved before use according to the supplied shipping documentation. 
The investigator, or designee, will ensure that all study products are stored in a secured area 
with controlled access under required storage conditions and in accordance with applicable 
regulatory requirements and the product label.   
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations (as 
applicable, including frozen, refrigerated, and/or room-temperature products).  This should be 
captured from the time of first product receipt throughout the study.  Even for continuous 
monitoring systems, a log or site procedure that ensures active daily evaluation for excursions 
should be available.  The operation of the temperature-monitoring device and storage unit (for 
example, refrigerator), as applicable, should be regularly inspected to ensure it is maintained 
in working order.  
Any excursions from the product-label storage conditions should be reported to appropriate 
site staff upon discovery and communicated to sponsor as soon as possible.  The site should 
actively pursue options for returning the product to the storage conditions as described in the 
labeling, as soon as possible.  Excursions from the storage requirements, including any actions 
taken, must be documented as a protocol deviation and reported to the Sponsor.   
Once an excursion is identified, the affected product (or products) must be quarantined and 
not used until the sponsor provides documentation of permission to use. Use of any of the 
affected product(s) prior to sponsor approval will be considered a protocol deviation.   
Site staff will instruct subjects on the proper storage requirements for all take-home products, 
as per the labels. 
6.4 
Investigational/Study Product Accountability 
All products supplied are for use only in this clinical study and should not be used for any 
other purpose. 
All study products must be received by a designated person at the study sites, handled and 
stored safely and properly, and kept in a secured location to which only the staff have access. 
Upon receipt, all study products should be stored according to the instructions specified on the 
product labels. Study products are to be dispensed only to subjects enrolled in the study in 
accordance with the protocol, by authorized site staff. 
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The investigative site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of all the product supplies. All study products will be accounted for using the 
investigational/study product accountability form/record. The investigator is responsible for 
study product accountability, reconciliation, and record maintenance.  
The accountability records must be available for inspection by the study monitor during the 
study. Monitoring of product accountability will be performed by the monitor during site 
visits and at the completion of the study.  
Subjects should return all products to the study site 
6.4.1 
Destruction of Investigational/Study Product Supplies  
At the end of the study, the Principal Investigator or an appropriate designee, and a 
representative of GSK CH (study monitor) will inventory all used and unused study products 
and sundry items.  The study product accountability record for returned study products will 
then be completed. All study product (used and unused) for this clinical study (including 
empty containers), will be returned for destruction to the GSK CH Clinical Supplies 
Department or designated vendor using the return instructions provided. Detailed instructions 
for the return of study product for the accountability checks and subsequent destruction will 
be provided by GSK CH during the study in time for study close out visit. 
6.5 
Blinding and Allocation/Randomization 
All subjects will be centrally randomized to one of the 3 study arms using an Interactive 
Response Technology (IRT). Before the study is initiated, training, login information and 
directions for the IRT will be provided to the site. Study products will be dispensed according 
to the instruction received through the IRT at the appropriate study visit. 
The Sponsor will provide 2 randomization schedules; one will be a randomization schedule 
for the allocation of study product to subject, and a second one for the LAST allocation per 
Lactic Acid Stinging Test (LAST), for the left and right side of the nasolabial fold, to ensure a 
balanced randomization of the two solutions (lactic acid and saline solution) for the screened 
subjects.  
Subjects will be randomized into the study and receive product provided they have satisfied 
all subject selection criteria.  
Returned study products should not be re-dispensed to any subject. 
The investigator’s knowledge of the product allocation should not influence the decision to 
enroll a subject or affect the order in which subjects are enrolled. 
This study is described as examiner-blind (the clinical examiners (dermatologist, 
ophthalmologist) will be blinded to the product the subject received).  
To ensure the examiner remains blinded throughout the study, staff involved in the dispensing 
of study products will work in a separate area. The examiner is not permitted in any area 
where study product is stored, dispensed, or in use.  
Subjects will be instructed not to remove study products outside of the dispensing room, while 
at the study site. Dispensing staff will not be involved in any safety assessment procedures 
during the study.   
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6.6 
Breaking the Blind 
At the initiation of the study, the study site will be instructed on the method for breaking the 
blind.  The method will be an electronic process. 
The electronic system will be programmed with blind-breaking instructions. In case of an 
emergency, the investigator has the sole responsibility for determining if unblinding of a 
subject’s product assignment is warranted. Subject safety must always be the first 
consideration in making such a determination. If the investigator decides that unblinding is 
warranted, the investigator should make every effort to contact the sponsor prior to unblinding 
a subject’s product assignment unless this could delay emergency treatment of the subject. 
If a subject’s product assignment is unblinded, the sponsor must be notified within 24 hours 
after breaking the blind. The date and reason that the blind was broken must be recorded in 
the source documentation and case report form, as applicable. 
Any AE associated with breaking the blind must be recorded and reported as specified in this 
protocol. The study site may also be required to inform the EC if the blind is broken.  
6.7 
Compliance 
Study products will be applied under the supervision of investigator site personnel for the first 
application at the study site.   
A paper diary will be supplied to promote compliance and to capture details of product use 
throughout the study period. Subjects may also record additional information such as AEs or 
medications used during the home use period in the provided diary. Any additional details 
relevant to safety that have been captured in the paper diary should be reviewed by the 
investigator (or suitably qualified designee) with the subjects and transcribed to the CRF (in 
English) as appropriate. 
The number of any missed or additional applications will be captured as protocol deviations 
and transcribed from the diary into the CRF. Subjects will be instructed in the correct usage 
requirements and diary completion post randomization at the first supervised product 
application. 
6.8 
Concomitant Medication/Treatment(s) 
Any medications, treatments or vaccinations (including over-the-counter or prescription 
medicines, vitamins, and/or herbal supplements) taken during the study, from signing the 
informed consent, must be recorded in the CRF with indication, reason for use, unit dose, 
daily dose, and start and stop dates of administration.  All subjects will be questioned about 
medications and treatments at each site visit. 
Medication/treatments taken within 30 days of signing the informed consent form will be 
documented as a prior medication/treatment.  Medications/treatments taken after the first 
supervised test product application (serum, lotion or cream) will be documented as 
concomitant medication/treatments. 
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7 
DISCONTINUATION OF STUDY INTERVENTION AND 
SUBJECT DISCONTINUATION/WITHDRAWAL 
7.1 
Subject Discontinuation/Withdrawal  
A subject may withdraw from the study at any time at his or her own request or may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety, behavioral 
reasons, or the inability of the subject to comply with the protocol-required schedule of study 
visits or procedures.   
The following circumstances require discontinuation of study product and/or premature 
subject withdrawal: 
 Protocol violation that may impact the subject’s safety 
 Withdrawal of informed consent 
 Subject lost to follow-up  
 Unblinding of the subject  
 Pregnancy 
If a subject is discontinued or prematurely withdraws from the study, the reason(s) for 
discontinuation or withdrawal and the associated date must be documented in the relevant 
section(s) of the CRF.  
7.2 
Lost to Follow up 
If a subject fails to return to the site for a required study visit the site must attempt to contact 
the subject and reschedule the missed visit as soon as possible and counsel the subject on the 
importance of maintaining the assigned visit schedule and ascertain whether the subject 
wishes to and/or should continue in the study. 
A subject will be considered lost to follow up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. Before a subject is deemed 
lost to follow up, the investigator or designee must make every effort to regain contact with 
the subject (where possible, 3 telephone calls and, if necessary, a certified letter to the 
subject’s last known mailing address or local equivalent methods). These contact attempts 
should be documented. If contact is made with the subject, the investigator should inquire 
about the reason for withdrawal, request that the subject return all products that they had been 
dispensed and if appropriate request that the subject return for a final visit and follow-up with 
the subject regarding any unresolved adverse events (AEs). 
Final safety assessments may be carried out when the subject returns to the study site, at the 
investigator’s discretion, which could include the following: 
 Dermatologist assessment of cutaneous irritation 
 Ophthalmologist assessment of ocular irritation 
 Subject self-assessment questions  
Should the subject continue to be unreachable, he/she will be considered to have withdrawn 
from the study and lost to follow up.  
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Lack of completion of all or any of the early termination procedures will not be viewed as 
protocol deviations so long as the subject’s safety was preserved. 
If the subject withdraws from the study and withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be 
collected.  The sponsor may retain and continue to use any data collected before such 
withdrawal of consent. 
8 
STUDY PROCEDURES 
This section lists the procedures to be completed at each planned study visit.  The timing of 
each procedure is listed in the Schedule of Activities. 
Adherence to the study design requirements, including all procedures are essential and 
required for study conduct. 
8.1 
Visit 1 (Day -6 to 0) Screening 
Screening procedures will be conducted by the Investigator, or suitably qualified designees. 
The following procedures will be completed: 
8.1.1 
Informed Consent 
The investigator, or designee, must obtain informed consent from each subject participating in 
this study after adequate explanation of the aims, methods, objectives, and potential hazards 
of the study. Two copies of the informed consent form (ICF) will be signed and dated by the 
subject, the subject will retain one copy and the other will be kept at site. 
The investigator, or designee, must also explain to the subjects that they are completely free to 
refuse to enter the study or to withdraw from it at any time.  Appropriate forms for 
documenting a signed and dated consent will be provided by either the investigator or by GSK 
CH. 
The investigator, or designee, should sign and date each copy of the ICF to confirm that the 
consent process was completed correctly after the subject has signed.   
The time the subject signed the informed consent form will also be documented as this is the 
point at which all AE’s will be captured from. The date and time of consent will be 
transcribed to the CRF. 
If, during a subject’s participation in the study, any new information becomes available that 
may affect the subject’s willingness to participate in the study, each ongoing subject should 
receive a copy of this new information and be re-consented into the study. Each subject 
should be provided with a copy of the signed and dated amended consent form. The date of 
re-consent will be recorded on the CRF. 
After signing the ICF, subjects will undergo the screening assessments to confirm that they 
meet the inclusion criteria and none of the exclusion criteria. If the subject is confirmed 
eligible by the investigator (or designee) to participate in the study the subject is considered 
enrolled in the study. 
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8.1.2 
Demographics 
The following demographic information will be recorded in the CRF: year of birth and race. 
Fitzpatrick skin type assessment APPENDIX 2 – FITZPATRICK SKIN TYPE GRADING 
will also be captured. The Fitzpatrick skin type scale is a numerical classification that is 
widely used by dermatologists to classify a person’s skin type by their response to sun 
exposure (Fitzpatrick, 1988). The classification of a subject’s Fitzpatrick skin type will be 
conducted by a trained evaluator. 
Race of subjects will be recorded in accordance with FDA Guidance for Industry: Collection 
of Race and Ethnicity Data in Clinical Trials, 2005.  
8.1.3 
Medical History Current and Prior Medication/Treatment 
Details of relevant medical and surgical history (in the last year), including allergies or drug 
sensitivity, will be documented in the CRF. 
Prior medications/treatments, including prescription and non-prescription drugs, dietary 
supplements and herbal remedies, taken in the last 30 days and prior to first product 
application, will be documented in the CRF. 
8.1.4 
Inclusion/Exclusion Criteria 
Review of inclusion and exclusion criteria as appropriate for the visit and information will be 
documented in the CRF. 
8.1.5 
Lactic Acid Stinging Test (LAST) 
Subjects will be instructed to wash their face with room-temperature tap water and to pat dry 
with paper towels provided by the investigational site. This will ensure a clean surface with 
which to conduct the LAST.  
Approximately 30 minutes after washing, a trained technician will apply an aqueous solution 
of 10% lactic acid to one nasolabial fold and a saline solution (0.9 Molar) to the other 
nasolabial fold in the following manner:  
The test substances (10% lactic acid; 0.9M NaCl) will be applied concurrently to either the 
right or the left nasolabial fold. The Sponsor will provide a randomization schedule for the left 
and right side of the face to have a balanced randomization of the two solutions for the 
screened subjects. 
 A separate swab will be dipped into each test solution (lactic acid and saline solution) 
 Each swab will be applied to the upper end of the nasolabial fold and moved in a 
circular area across the infraorbital part of the cheek under the outer corner of the eye 
and back along the fold of the nostrils, and along the nasolabial fold to the side of the 
corner of the mouth, ending at the point where the application started. (See Figure 8-1 
as an example).  
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Figure 8-1 
 
 The complete movement will be repeated once more. 
 The applied test substances should not extend beyond this area.  
 For each subject, fresh swabs will be used. 
Subjects will be asked to report any sensations of discomfort 2-3 minutes and 5-6 minutes 
after application of the solutions on a 4-point scale (Christensen and Kligman, 1996) per 
Table 8-1. Scores will be entered into the CRF by a technician.  
The test will be suspended after 6 minutes if no local sensation is reported, or immediately 
upon any reported score of 3. The subjects will be instructed to remove the solutions by 
thoroughly washing with room-temperature tap water and drying their face with a paper 
towel. 
The sum of the 2-3 and 5-6-minute subject self-assessment scores will be calculated in the 
CRF for the lactic acid and saline-treated nasolabial folds.  
Subjects who report a total score ≥2 for the lactic acid-treated site compared to the saline-
treated site will be considered to have had a positive response to the LAST. Otherwise, 
subjects will be considered to have had a negative response to the LAST. Only subjects with a 
positive response to the LAST will be enrolled into the study. 
Table 8-1 
Lactic Acid Sting Test Score 
Score 
Description 
0 
No discomfort/sensation 
1 
Mild discomfort/stinging 
2 
Moderate discomfort/stinging 
3 
Severe discomfort/stinging 
Sensations of discomfort may or may not appear. In instances where sensations of discomfort 
do appear, they may go unnoticed for 1-2 minutes at the start but should intensify up to 5-6 
minutes.  
Any observed response that can be denoted according to the score of the reactions (per Table 
8-1) will not be considered an adverse event. Only in the case of unusual reactions, in the 
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opinion of the qualified dermatologist, will these reactions and the consequences observed 
upon evaluation be documented as AE’s. 
The subject will not be informed which nasolabial fold received the lactic acid solution and 
which nasolabial fold received saline solution. 
If Visit 2 is combined with Visit 1, the dermatologist and ophthalmologist assessments and 
the subject self-assessments will be conducted prior to the LAST. Eligible subjects will not 
apply study product until at least 30 minutes following the end of the LAST. 
8.1.6 
Subject Eligibility 
The investigator and/or medically qualified designee will review inclusion and exclusion 
criteria, medical history, prior medications, etc.  to confirm subject eligibility to participate in 
the clinical trial. This will be documented in the CRF. 
To prepare for study participation, subjects will be instructed in the Lifestyle Considerations 
of the protocol. 
8.2 
Visit 2 (Day 1) Baseline/Randomization 
Visit 2 may be combined with Visit 1. If Visit 2 is not combined with Visit 1, Visit 2 must 
occur within 7 calendar days of Visit 1. 
8.2.1 
Medical History and Prior Medication/Treatment 
Review of medication/treatments, all information will be documented in the CRF. 
8.2.2 
Subject self-assessment 
Subjects will be asked to answer the self-assessment questions as per section Subject Self-
Assessment of Signs and Symptoms of Cutaneous and Ocular Irritation prior to randomization 
and any product application (baseline). Subject responses will be directly entered into the 
CRF by site staff. 
The self-assessment questions will be asked again 1-2 hours following first supervised 
product use. Subject responses will be directly entered into the CRF by site staff. 
If Visit 2 is combined with Visit 1, the initial (baseline) subject self-assessments will be 
conducted after the initial (baseline) dermatologist and ophthalmologist assessments. These 
assessments will be conducted prior to the LAST procedure and first product application. 
8.2.3 
Dermatologist Assessment 
A qualified dermatologist will visually assess the subject at Visit 2 (baseline) prior to 
randomization to determine subject’s eligibility to continue in the study. This will ensure the 
subject is free of any preexisting dermatological pathology prior to using the study products 
(Edward and Norman, 1982).   
Subjects will only be considered eligible to enter the study if they have a dermatologist signs 
and symptoms cutaneous irritation score of 0.5 (very slight) or greater for erythema and 
dryness and a score of 0 (none) or 0.5 (very slight) for scaling and edema, as this is 
representative of the target consumer for the finished product. Subjects presenting with a 
score of 1 (slight) or greater for edema are excluded from the study as this condition is not 
reflective of the target population.  
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Any subject with a score of 3 (severe) in any attribute will exclude the subject from the study, 
as this condition is not reflective of the target population for the product. 
The intensity of any visual signs of dermal irritation will be recorded according to the grade of 
the reactions per the Dermatological Evaluation (Safety and Other Assessments). The 
dermatologist is responsible for grading the level of cutaneous irritation and their opinion on 
the correct classification of the irritation scores is final. Scores will be directly entered into the 
CRF. 
Any observed cutaneous response that can be denoted according to the grade of the reactions 
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.  
If Visit 2 is combined with Visit 1, the initial (baseline) dermatologist assessment will be 
conducted prior to the LAST procedure. Randomization and initial test product application 
will occur at least 30 minutes after the LAST procedure. 
8.2.4 
Ophthalmologist Assessment 
A qualified ophthalmologist will assess the subject at Visit 2 (baseline) prior to randomization 
to determine their subjects to continue in the study. This will ensure the subject is free of any 
preexisting ophthalmological pathology prior to using the study products (Edward and 
Norman, 1982). For inclusion into the study each subject should have a total ocular irritation 
score of 0 (none).  
The intensity of any visual signs of ocular irritation will be recorded according to the grade of 
the reactions according to the Ophthalmological Evaluation (Safety and Other Assessments). 
The ophthalmologist is responsible for grading the reactions, their opinion on the 
classification of the ocular irritation scores is final. Scores will be directly entered into the 
CRF. 
Any observed ocular response that can be denoted according to the grade of the reactions 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. 
If Visit 2 is combined with Visit 1, the initial (baseline) ophthalmologist assessment will be 
conducted prior to the LAST procedure and any test product application. Randomization and 
initial test product application will occur at least 30 minutes after the LAST procedure. 
8.2.5 
Supervised Product Application 
Subjects will be asked to answer the self-assessment questions as per section Subject Self-
Assessment of Signs and Symptoms of Cutaneous and Ocular Irritation prior to randomization 
and any product application (baseline). Subject responses will be directly entered into the 
CRF by site staff. 
The first subject application of the assigned product will be conducted by the subject under 
the supervision of a trained technician at the study site at Visit 2 (baseline) following 
completion of the baseline dermatologist and ophthalmologist assessments and the subject 
self-assessment questions. Subjects will perform a second application of their assigned 
product at home that evening.  
Subjects will then continue to use the product at home, twice a day (morning and evening) 
during the study period, for a total of 21 (+ 2) days, including the morning of the final visit 
and will be instructed to contact the study site if they have any reactions.  
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Sufficient product will be provided to last the duration of the study. Subjects will be dispensed 
a paper diary alongside their assigned product to be completed at home to record product use.  
If Visit 1 and Visit 2 are combined, there should be a minimum of 30 minutes after the 
LAST has completed before any product application. First application of the assigned 
product will be conducted by the subject under the supervision of a trained technician at the 
site following completion of the baseline dermatologist and ophthalmologist assessments 
and subject self-assessment questions.  
The self-assessment questions will be asked again 1-2 hours following first supervised 
product use. Subject responses will be directly entered into the CRF by site staff. 
Spontaneous reporting of AE’s and those elicited by asking subjects to respond to a 
non-leading question such as “How do you feel?” will be assessed and any AEs recorded in 
the CRF. 
8.3 
Visit 3/Day 21 (Final Visit) 
Changes in concomitant medication or non-drug treatments/procedures will be documented in 
the CRF.  
Spontaneous reporting of AE’s, AE’s captured in the subject diary card, and those elicited by 
asking subjects to respond to a non-leading question such as “How do you feel?” will be 
assessed and any AEs recorded in the CRF. 
8.3.1 
Dermatologist Assessment 
A final assessment by the same dermatologist, where possible, will be completed at the end of 
the 21 (+2) day product use period (Visit 3).  
The intensity of any visual signs of dermal irritation will be recorded according to the grade of 
the reactions according to the Dermatological Evaluation (Dermatologist Assessment of Signs 
and Symptoms of Cutaneous Irritation). 
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 response that can be denoted according to the grade of the reactions 
will not be considered an adverse event. Only in the case of unusual reactions, in the opinion 
of the qualified dermatologist, will these reactions and the consequences observed upon 
evaluation be documented as AE’s.  
8.3.2 
Ophthalmologist Assessment 
A final assessment by the same ophthalmologist, where possible, will be completed at the end 
of the 21 (+2) day product use period (Visit 3).  
The intensity of any visual signs of ocular irritation will be recorded according to the grade of 
the reactions according to the Ophthalmological Evaluation (Ophthalmologist Assessment of 
Signs and Symptoms of Ocular Irritation). 
The ophthalmologist is responsible for grading the reactions, their opinion on the 
classification of the ocular irritation scores is final. 
Any observed ocular response that can be denoted according to the grade of the reactions will 
not be considered an adverse event. Only in the case of unusual reactions, in the opinion of 
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Protocol Number: 213059  
 
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the qualified ophthalmologist, will these reactions and the consequences observed upon 
evaluation be documented as AE’s. 
8.3.3 
Subject self-assessment 
Subjects will be asked to answer the final self-assessment questions as per section Subject 
Self-Assessment of Signs and Symptoms of Cutaneous and Ocular Irritation at the end of the 
21 (+2) day product use period. Subject responses will be directly entered into the CRF by site 
staff.  
8.4 
Diary Review 
The diary will be reviewed by the investigator, or suitably qualified designee, and the subject. 
Any subject comment captured in the diary which is considered an adverse event will be 
assessed and reported as per the defined procedure in this protocol. Adverse event reporting 
procedures are summarized in Adverse Event and Serious Adverse Events.  
Any additional comments relating to medications/treatments provided in the diary will be 
reviewed by the investigator or medically qualified designee with the subject and entered into 
the CRF as appropriate.  
Additional and missed product applications will be considered deviations from the protocol 
and will be recorded on the Deviations Log of the CRF.  
8.5 
Study Conclusion 
The Study Conclusion page of the CRF will be completed for all subjects whether they 
completed all study procedures or if they were discontinued from the study early.  If the 
subject discontinued early, at any point during the study, the primary reason for withdrawal 
should be recorded on the Study Conclusion page. 
If a subject has any clinically significant, study-related abnormalities or AEs at the end of the 
study, the GSK CH medical monitor (or designated representative) should be notified and, the 
subject may be asked to remain at the clinical site or be asked to return for a follow-up visit to 
ensure any issue is resolved or deemed not clinically significant.  
8.6 
Follow-up Visit 
The study site may contact a subject to follow up an AE post-study completion/withdrawal 
and, in some circumstances, request they return to the site for additional follow-up visits (final 
safety (dermatologist and ophthalmologist assessments). If needed, additional examinations 
may be carried out at such visits. 
9 
STUDY ASSESSMENTS 
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances, outside the control of the investigator that may make it unfeasible to complete 
an assessment.  In these cases, the investigator must take all steps necessary to ensure the 
safety and well-being of the subject.  When a protocol-required assessment cannot be 
performed, the investigator (or designee) will document the reason for the missed assessment 
as a protocol deviation and any corrective and preventative actions that he or she has taken to 
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ensure that required processes are adhered to as soon as possible.  The Sponsor must be 
informed of any missed assessments in a timely manner. 
9.1 
Screening Assessments 
Screening assessments will be performed by appropriately trained staff/clinical examiners at 
the times, and in the order, defined in the Study Procedures section of this protocol  
9.2 
Safety and Other Assessments 
The following safety assessments will be performed by appropriately trained staff/clinical 
examiners, at the times and in the order defined in the Schedule of Activities section of this 
protocol. 
9.2.1 
Dermatologist Assessment of Signs and Symptoms of Cutaneous 
Irritation 
A qualified dermatologist will visually assess the signs and symptoms of cutaneous irritation. 
The following grades and their respective numerical equivalent scores will be used to record 
the response observed at the time of clinical examination at baseline (prior to product 
application), and the final visit. 
Table 9-1 
Dermatological Evaluation 
For any subject who presents an increased score versus baseline, the dermatologist will further 
classify whether the reaction constitutes a clinically relevant positive outcome.  
9.2.2 
Ophthalmologist Assessment of Signs and Symptoms of Ocular 
Irritation 
A qualified ophthalmologist will visually assess the signs and symptoms of ocular irritation. 
The following grades and their respective numerical equivalent scores will be used to record 
the response observed at the time of examination at baseline (prior to product application), 
and the final visit. 
Table 9-2 
Ophthalmological Evaluation 
Attribute 
Description (Score) 
Erythema 
None (0) 
Very Slight (0.5) 
Slight (1) 
Moderate (2) 
Severe (3) 
Dryness 
None (0) 
Very Slight (0.5) 
Slight (1) 
Moderate (2) 
Severe (3) 
Scaling 
None (0) 
Very Slight (0.5) 
Slight (1) 
Moderate (2) 
Severe (3) 
Edema 
None (0) 
Very Slight (0.5) 
Slight (1) 
Moderate (2) 
Severe (3) 
Attribute 
Description (Score) 
Eczema of the 
eyelid 
None (0) 
Very Slight (0.5) 
Slight (1) 
Moderate (2) 
Severe (3) 
Conjunctivitis 
None (0) 
Very Slight (0.5) 
Slight (1) 
Moderate (2) 
Severe (3) 
Follicles 
None (0) 
Very Slight (0.5) 
Slight (1) 
Moderate (2) 
Severe (3) 
Chemosis 
conjunctivae 
None (0) 
Very Slight (0.5) 
Slight (1) 
Moderate (2) 
Severe (3) 
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For any subject who presents an increased score versus baseline, the ophthalmologist will 
further classify whether the reaction constitutes a clinically relevant positive outcome.  
9.2.3 
Subject Self-Assessment of Signs and Symptoms of Cutaneous and 
Ocular Irritation 
Subjects will be asked to self-assess any sensations of cutaneous and ocular discomfort that 
they are currently experiencing. The following grades and their respective numerical 
equivalent scores will be used to record the subjects’ response at baseline (prior to product 
application), 1-2 hours following first product application and at the final visit. 
Table 9-3 
Subject Self-Assessment Scale for Signs and Symptoms of 
Cutaneous Irritation 
Attribute 
 
Description (Score) 
Redness 
None (0) 
Very Slight (0.5) 
Slight (1) 
Moderate (2) 
Severe (3) 
Dryness 
None (0) 
Very Slight (0.5) 
Slight (1) 
Moderate (2) 
Severe (3) 
Stinging/Burning 
None (0) 
Very Slight (0.5) 
Slight (1) 
Moderate (2) 
Severe (3) 
Itching 
None (0) 
Very Slight (0.5) 
Slight (1) 
Moderate (2) 
Severe (3) 
Tightness 
None (0) 
Very Slight (0.5) 
Slight (1) 
Moderate (2) 
Severe (3) 
Table 9-4 
Subject Self-Assessment Scale for Signs and Symptoms of Ocular 
Irritation 
Attribute 
 
Description (Score) 
Redness 
None (0) 
Very Slight (0.5) 
Slight (1) 
Moderate (2) 
Severe (3) 
Dryness 
None (0) 
Very Slight (0.5) 
Slight (1) 
Moderate (2) 
Severe (3) 
Stinging/Burning 
None (0) 
Very Slight (0.5) 
Slight (1) 
Moderate (2) 
Severe (3) 
Itching 
None (0) 
Very Slight (0.5) 
Slight (1) 
Moderate (2) 
Severe (3) 
9.2.4 
Pregnancy Testing 
For GSK CH studies in which no drug is utilized or studies of single-use marketed products 
that are classified as a non-medicinal product in the market where the testing is occurring and 
there is no pregnancy warning on labelling, a pregnancy test will not be required. 
Subjects will need to provide verbal confirmation of negative pregnancy status and this must 
be documented as part of the exclusion criteria. 
10 
ADVERSE EVENT AND SERIOUS ADVERSE EVENTS 
The investigator and any qualified designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE and remain responsible for 
following up AEs that are serious, considered related to the study product or the study, or that 
caused the subject to discontinue the study product or study 
10.1 
Definition of an Adverse Event (AE) 
An AE is any untoward medical occurrence in a clinical study subject, temporally associated 
with the use of a study product including any washout or lead-in product (or medical device), 
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whether or not considered related to the study product, including any washout or lead-in 
product (or medical device). 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of a study product including any washout or lead-in product (or medical device). 
Events Meeting the AE Definition:   
 Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g. ECG, radiological scans, vital sign measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator (i.e., not related to progression of 
underlying disease). 
 Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
 New conditions detected or diagnosed after study product administration even though 
it may have been present before the start of the study. 
 Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
 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 unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdoses should be reported regardless of sequelae. 
Events NOT meeting the AE definition:  
 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.  
 The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the subject’s 
condition.  
 Medical or surgical procedure (e.g. endoscopy, appendectomy) is not the AE. The 
condition that leads to the procedure is an AE (e.g. appendicitis). 
 Situations where an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
 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.  
 Any observed response to the LAST that can be denoted according to the score of the 
reactions (per Table 8-1 Lactic Acid Sting Test Score) will not be considered an 
adverse event. Only in the case of unusual reactions, in the opinion of the qualified 
dermatologist, will these reactions and the consequences observed upon evaluation be 
documented as AE’s. 
 Any observed cutaneous or ocular response that can be denoted according to the grade 
of the reactions (per Safety and Other Assessments) will not be considered an adverse 
event. Only in the case of unusual reactions, in the opinion of the clinical expert, will 
these reactions and the consequences observed upon evaluation be documented as 
AEs. 
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10.2 
Definition of a Serious Adverse Event (SAE) 
A Serious Adverse Event (SAE) is a particular category of an adverse event where the adverse 
outcome is serious. If an event is not an AE per definition above, then it cannot be an SAE 
even if serious conditions are met (e.g. hospitalization for signs/symptoms of the disease 
under study, death due to progression of disease). 
A serious adverse event is any untoward medical occurrence at any dose that: 
 Results in death 
 Is life-threatening  
 The term 'life-threatening' in the definition of 'serious' refers to an event in which 
the subject was at risk of death at the time of the event. It does not refer to an 
event, which hypothetically might have caused death, if it were more severe; 
 Requires inpatient hospitalization or prolongation of existing hospitalization  
 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 outpatient 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. 
 Results in persistent or significant disability/incapacity 
 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 with or 
prevent everyday life functions but do not constitute a substantial disruption 
 Results in congenital anomaly/birth defect 
 Other situations: 
 Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the subject or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should usually be considered serious. 
 Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse. 
Note: Classification of an AE as ‘serious’ is based on the outcome of the event and is a factor 
in determining reporting requirements. 
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10.3 
Time Period and Frequency for Collecting AE and SAE 
Information 
All AEs, and therefore all SAEs will be collected immediately after a subject provides consent 
to participate in the study by the completion (signature) of the ICF and until 5 days following 
last administration of the study product (or last procedure).  
Medical occurrences that began before obtaining informed consent will be recorded in the 
Medical History/Current Medical Conditions section of the CRF not the AE section. 
Details recorded by the subject on a diary or similar document that meet the definition of an 
AE must also be discussed with the subjects and transcribed in the AE section of the CRF.  
All SAEs will be recorded and reported to the sponsor or designee immediately and under no 
circumstance should this exceed 24 hours. The investigator will submit any updated SAE data 
to the sponsor within 24 hours of it being available. 
Investigators are not obligated to actively seek AEs or SAEs after the conclusion of the study 
participation. However, if the investigator learns of any SAE, including a death, at any time 
after a subject has been discharged from the study, and he/she considers the event to be 
reasonably related to the study product or study participation, the investigator must promptly 
notify the sponsor. 
10.4 
Reporting Procedures 
The investigator and any designees are responsible for detecting, documenting and reporting 
events that meet the definition of an AE and remain responsible for following up on AEs that 
are serious, considered related to the study product(s), participation in the study, or a study 
procedure, or that caused the subject to discontinue the study product or study.  
Spontaneous reporting of adverse events and those elicited by asking subjects to respond to 
non-leading such as “How do you feel” will be assessed and any AE’s recorded in the CRF 
and reported appropriately. 
The investigator (or medically qualified designee) is to report all directly observed AEs and 
all AEs spontaneously reported by the study subject. In addition, each study subject will be 
questioned about AEs.  
Each AE is to be assessed to determine if it meets the criteria for a SAE.  If an SAE occurs, 
expedited reporting will follow local and international regulations, as appropriate. 
When an AE occurs, it is the responsibility of the investigator (or medically qualified 
designee) to review all documentation (e.g. hospital progress notes, laboratory, and 
diagnostics reports) related to the event. 
The investigator or site staff will then record all relevant information regarding an AE in the 
CRF and all details relating to an SAE in the paper SAE Form provided. 
It is not acceptable for the investigator (or medically qualified designee) to send photocopies 
of the subject’s medical records to GSK CH in lieu of completion of the AE CRF page/SAE 
form. 
There may be instances when copies of medical records for certain cases are requested by 
GSK CH.  In this instance, all subject identifiers, except for the subject number, will be 
redacted on the copies of the medical records prior to submission to GSK CH. 
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The investigator (or medically qualified designee) will attempt to establish a diagnosis of the 
event based on signs, symptoms, and/or other clinical information.  The diagnosis will be the 
documented as the AE/SAE where known and not the individual signs/symptoms. (e.g. upper 
respiratory tract infection, seasonal allergy, etc. instead of runny nose). 
AEs elicited by the investigator (or medically qualified designee) in a standard manner at the 
study visits should also be recorded in the AE section of the CRF and/or using the SAE form 
(subject to the classification of the AE). Care will be taken not to introduce bias when 
questioning a subject about any changes in their health. Open-ended and non-leading verbal 
questioning should be used. 
10.4.1 
Reporting of an Adverse Event 
All AEs will be reported on the AE page of the CRF by the investigator or site staff.  It should 
be noted that the form for collection of SAE information is not the same as the AE CRF.  
Where the same data are collected, the AE CRF page and the SAE form must be completed in 
a consistent manner.  For example, the same AE term should be used on both.  AEs should be 
reported using concise medical terminology on the CRF as well as on the form for collection 
of SAE information. 
10.4.2 
Reporting of a Serious Adverse Event 
In addition to recording the details of each AE on the AE CRF page, an SAE form should be 
completed, as fully as possible. Hard copies of the ‘paper’ SAE form will be provided in the 
investigator study master file. Original SAE forms will be retained in the investigator study 
master file. 
It is essential to enter the following information:  
 Protocol and subject identifiers 
 Subject demography 
 Description of events, with diagnosis if available 
 Investigator opinion of relationship to study product (or study procedure, if 
appropriate) 
 Criterion for seriousness. 
The following are desirable and are of particular relevance for investigator and GSK CH 
assessment of the SAE report: 
 Date of onset of AE  
 Date AE stopped, if relevant 
 Study product start date 
 Study product end date if relevant 
 Action taken in relation to the study product 
 Outcome if known 
The SAE form, completed as fully as possible, must be scanned and e-mailed to the GSK CH 
Clinical Operations Safety Reporting email box with the study number and subject number in 
the subject line of the email immediately and under no circumstance should this exceed 24 
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G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 1 3 0 5 9  
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H  
S O P -2 0 8 6 6 1 Cli nical Pr ot oc ol Te m plate v 5. 0  
Pa ge 4 3  of 5 6  
h o urs  after st u d y site pers o n nel l ear n of t he e ve nt. T he i n vesti gat or will s u b mit a n y u p dat e d 
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sit uati o n b y t ele p h o ne or e mail. 
E m ail Seri o us A d verse E ve nts t o:  
 
T he G S K C H St u d y Ma n a ger or d esi g n ee will be res p o nsi ble f or f or war di n g t he S A E f or m t o 
t he Case 
Ma na ge me nt 
Gr o u p, 
Gl o bal Cli nical Safet y a n d P har mac o vi gila nce 
mail b o x 
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T he i nitial re p ort will be f oll o we d u p wit h m ore i nf or mati o n as rele va nt, or as re q u este d b y 
t he G S K C H st u d y ma na ger. 
1 0. 5  
E v al u ati n g A d v er s e E v e nt s  
1 0. 5. 1  
A s s e s s m e nt  of I nt e n sit y  
T he i n vesti gat or or me dicall y q u alifie d desi g nee will ma ke a n assess me nt of i nte nsit y f or eac h 
A E re p orte d d uri n g t he st u d y a n d will assi g n it t o o ne of t he f oll o wi n g cate g ories:  
 Mil d:  A n e ve nt t hat is easil y t olerat e d b y t he s u bject, ca usi n g mi ni mal disc o mf ort a n d 
n ot i nterferi n g wit h e ver y d a y acti vities.  
 M o derate:  A n e ve nt t hat is s ufficie ntl y disc o mf orti n g t o i nterfere wit h n or mal 
e ver y da y acti vities  
 Se vere:  A n e ve nt t hat pr e ve nts n or mal e ver y da y acti vities.  
N O T E: A n A E t hat is assesse d  as se vere s h o ul d n ot be c o nf use d wit h a n S A E. Se vere is a 
cate g or y utilize d f or rati n g t he i nte nsit y of a n e v e nt; a n d b ot h n o n -seri o us A Es a n d S A Es ca n 
be assesse d as s e vere. F or e x a m ple, a h ea dac he ma y b e se v ere (i nterferes si g nifica ntl y wit h 
t he s u bject's us ual f u ncti o n) b ut w o ul d n ot be classifie d as seri o us u nless it met o ne of t h e 
criteria f or S A Es, liste d a b o ve. A n e ve nt is defi ne d as ‘seri o us’ w he n it meets at least 1 of t he 
pre defi n e d o utc o mes as d escri be d i n t he d efi niti o n of a n S A E, N O T w h e n it i s rate d as se vere. 
1 0. 5. 2  
A s s e s s m e nt of C a u s alit y  
T he ca us alit y assess me nt is o ne of t he criteria use d w he n d eter mi ni n g re g ul at or y re p orti n g 
re q uire me nts.  
F or eac h A E (seri o us a n d n o n -seri o us), t he i n v esti gat or ( or me dicall y q ualifie d desi g nee) 
m ust  pr o vi de a n a ssess me nt of ca usalit y o n t he A E C R F pa ge a n d t he S A E f or m (s u bject t o 
t he classificati o n of t he A E). T he i n vesti gat or will als o d oc u me nt i n t he me dical n otes t h at 
he/s he has re vi e we d t he A E a n d assess e d ca us alit y, w here a p plica ble.  
A “reas o na ble p ossi bil it y” of a rel ati o ns hi p c o n ve ys t hat t here are facts, e vi de nce, a n d/ or 
ar g u me nts t o s u g gest a ca usal rel ati o ns hi p, rat her t ha n a relati o ns hi p ca n n ot be r ule d o ut. 
Ge nerall y, t he facts (e vi de nce) or ar g u me nts t o s u g gest a ca usal relati o ns hi p s h o ul d be 
pr o vi d e d. 
T he i n vesti gat or will use cli nical j u d g me nt t o deter mi ne t he relati o ns hi p a n d will als o c o ns ult 
t he Safet y State me nt , i n t he deter mi nati o n of his/ her assess me nt.  Alter nati ve ca uses, s uc h as 
2 1 3 0 5 9 | Pr ot oc ol Cli nical Pr ot oc ol 1 0 Mar 2 0 2 0 | T M F- 1 8 4 3 3 3 | 1. 0
P P D
P P D

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 1 3 0 5 9  
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H  
S O P -2 0 8 6 6 1 Cli nical Pr ot oc ol Te m plate v 5. 0  
Pa ge 4 4  of 5 6  
u n derl yi n g diseas e(s), c o nc o mita nt t hera p y, ot her ris k fact or s, a n d t he te m p oral relati o ns hi p of 
t he e ve nt t o t he st u d y pr o d uct will be c o nsi dere d a n d i n vesti gate d. 
F or eac h A E/ S A E, t he i n vesti gat or m ust d oc u me nt i n t he me dical n otes t hat he/s he has 
re vie we d t h e A E/ S A E a n d has pr o vi de d a n assess me nt of ca usalit y. 
T h e i n vesti gat or’s assess me nt of ca usalit y m ust be pr o vi d e d f or all A Es (seri o us a n d n o n -
seri o us); t he i n vesti gat or m ust rec or d t he ca usal relati o ns hi p i n t he C R F, as a p pr o pri ate, a n d 
re p ort s uc h a n assess me nt i n acc or da n ce wit h t he S A E re p orti n g re q uir e me nts if a p plica ble. 
T here ma y b e sit uati o ns w he n a n S A E has o cc urre d, a n d t he i n vesti gat or h as mi ni mal 
i nf or mati o n t o i ncl u de i n t he i nitial re p ort t o G S K.  H o w e ver, it is ver y i m p ort a nt t h at t he 
i n vesti g at or al w a ys m a ke a n assess me nt of c a us alit y f or e ver y eve nt pri or t o t he i niti al 
tr a ns missi o n of t he S A E d at a t o G S K C H. T h e i n vesti gat or m a y c ha n ge his/ her o pi ni o n of 
ca usalit y i n li g ht of f oll o w -u p i nf or mati o n a n d se n d a n S A E f oll o w -u p re p ort wit h t he u p date d 
ca usalit y assess me nt.  
1 0. 6  
F oll o w -u p of A E s a n d S A E s   
After t he i nitial A E/ S A E re p ort, t he i n vesti gat or is re q uire d t o pr oacti vel y f oll o w u p wit h eac h 
s u bject a n d pr o vi de f urt h er i nf or mati o n o n t he s u bject’s c o n diti o n. 
All A Es (seri o us a n d n o n -seri o us) will be f oll o we d u ntil res ol uti o n, u ntil t he c o n diti o n 
sta bilizes, u ntil t he e ve nt is ot her wise e x plai ne d, or u ntil t he s u bject is l ost t o f oll o w-u p.   
T he i n vesti gat or is o bli gate d t o perf or m or arra n ge f or t he c o n d uct of s u p ple me ntal 
meas ure me nts a n d/ or e val uati o ns as ma y be i n dicate d or as re q ueste d b y G S K C H t o el uci date 
as f ull y as p ossi ble t he nat ure a n d/ or ca us alit y of t he A E. T his ma y i ncl u de a d diti o nal 
la b orat or y tests or i n vesti gati o ns, hist o pat h ol o gical e x a mi nati o ns, or c o ns ultati o n wit h ot her 
healt h care pr ofessi o nals.  
Ne w or u p d ate d i nf or m ati o n will  be rec or de d o n t he A E C R F pa ge a n d o n t he S A E f or m 
(s u bject t o t he classificati o n of t he A E). 
T he i n vesti gat or will s u b mit a n y u p date d S A E d ata t o G S K C H wit hi n 2 4 h o urs of recei pt of 
t he i nf or mati o n. 
I n v esti gat ors are n ot o bli ge d t o acti vel y see k A Es i n f or mer s u bjects.  H o we v er, if t he 
i n vesti gat or le ar ns of a S A E, i ncl u di n g d eat h, at a n y ti me after a s u bject h as bee n dis c har ge d 
fr o m t he st u d y, a n d c o nsi ders t he e ve nt reas o n a bl y rel ate d t o t he st u d y pr o d uct or st u d y 
partici pati o n, t he i n vesti gat or will p r o m ptl y n otif y G S K C H b y e maili n g t he i nf or mati o n t o 
t he 
G S K 
C H 
Cli nical 
O perati o ns 
Safet y 
Re p orti n g 
e mail 
b o x (
). T h e G S K C H St u d y 
M a n a ger or d esi g n ee will be res p o nsi ble f or 
f or war di n g t he i nf or mati o n t o t he Case 
Ma na ge me nt Gr o u p, Gl o bal Cli nical Safet y a n d 
P har mac o vi gila nce gr o u p mail b o x at G S K (
). 
T he i n vesti gat or will s u b mit a n y u p dat e d S A E data t o G S K C H wit hi n t he de si g n ate d 
re p orti n g ti me fra m es. 
1 0. 7  
Wit h dr a w al D u e t o a n A d v er s e E v e nt  
Wit h dra wal d ue t o A Es s h o ul d be disti n g uis h e d fr o m wit h dra wal d u e t o ot her ca uses, 
acc or di n g t o t he defi niti o n of a n A E n ote d earlier, a n d rec or de d o n t he a p pr o priate A E C R F  
pa ge.  
2 1 3 0 5 9 | Pr ot oc ol Cli nical Pr ot oc ol 1 0 Mar 2 0 2 0 | T M F- 1 8 4 3 3 3 | 1. 0
P P D
P P D

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 1 3 0 5 9  
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H  
S O P -2 0 8 6 6 1 Cli nical Pr ot oc ol Te m plate v 5. 0  
Pa ge 4 5  of 5 6  
W he n a s u bject wit h dra ws beca use of a n S A E, t he S A E m ust be re p orte d i n acc or da n ce wit h 
t he re p orti n g re q uire me nts defi ne d. 
1 0. 8  
R e g ul at or y R e p orti n g R e q uir e m e nt s f or S A E s 
G S K C H has a le gal res p o nsi bilit y t o n otif y, as a p pr o priate, t he l ocal re g ul at or y a ut h orit y a n d 
ot her re g ulat or y a ut h orities a b o ut t he safet y of a pr o d uct u n der cli nical i n vesti gati o n.  Pr o m pt 
n otificati o n of S A Es b y t he i n vesti gat or t o G S K C H is esse ntial s o t hat le gal o bli gati o ns a n d 
et hical res p o nsi bilities t o war ds t he safet y of s u bjects are met.  
G S K C H will c o m pl y wit h c o u ntr y s pecific re g ulat or y re q uir e me nts relati n g t o safet y 
re p orti n g t o t he re g ulat or y a ut h orit y, E C a n d i n vesti gat ors. 
B ot h t he i n vesti gat or a n d t he s p o ns or will c o m pl y wit h all l ocal me dical de vice re p orti n g 
re q uire me nts  
I n v esti gat or safet y re p orts 
m ust be pre p are d f or s us pecte d u ne x pecte d seri o us a d v erse 
reacti o ns ( S U S A R) acc or di n g t o l ocal re g ulat or y re q uire me nts a n d s p o ns or p olic y a n d 
f or war de d t o i n vesti gat ors as necess ar y. 
A n i n vesti gat or w h o recei ves a n i n vesti gat or safet y re p ort descri bi n g a S A E or ot her s pecific 
safet y i nf or mati o n e. g. s u m mar y or listi n g of S A E fr o m t he s p o ns or will re vie w a n d t he n file 
it al o n g wit h t he I n vesti gat or’s Br oc h ure i n t he i n vesti gat or st u d y master file, a n d will n otif y 
t he E C, if a p pr o priate acc or di n g t o l ocal re q uir e m e nts. 
1 0. 9  
Pr e g n a n c y  
1 0. 9. 1  
Ti m e P eri o d f or C oll e cti n g Pr e g n a n c y I nf or m ati o n  
Pre g n a nc y i nf or mati o n will be c ollecte d o n all pre g na nci es re p orte d w hile a fe male s u bject is 
partici pati n g i n t he st u d y fr o m t he si g ni n g of i nf or me d c o ns e nt u ntil  5 da ys aft er last 
a d mi nistrati o n of st u d y pr o d uct.  
1 0. 9. 2  
A cti o n t o b e T a k e n if Pr e g n a n c y O c c ur s  
T he i n vesti gat or will rec or d pre g n a nc y i nf or m ati o n o n t he a p pr o priate f or m sca n a n d e -mail it 
t o t he 
G S K 
C H 
Cli nical 
O perati o ns 
Safet y 
R e p orti n g e mail b o x (
) wit hi n 2 4 h o urs of lear ni n g of t he s u bject bec o mi n g pre g na nt. T he G S K 
C H St u d y Ma n a ger or d esi g nee will be res p o nsi ble f or f or war di n g t he pre g n a nc y f or m t o t h e 
Case 
Ma na ge me nt 
Gr o u p, 
Gl o bal 
Cli nical 
Safet y a n d 
P har mac o vi gila nce 
mail b o x 
(
). Ori gi nal pre g na n c y i nf or mati o n f or ms 
will be retai ne d i n t he 
i n vesti gat or st u d y master file.  
T he s u bject will be f oll o we d t o deter mi ne t h e o ut c o me of t he pre g na nc y. I nf or mati o n o n t he 
stat us of t he m ot her a n d i nfa nt / ne o n ate (i ncl u di n g c o nc o mita nt me dicati o ns ta ke n b y t h e 
m ot her d uri n g t he pre g n a nc y) will be f or war de d b y t he i n vesti gat or t o t he G S K C H Cli nical 
O perati o ns Safet y R e p orti n g e mail b o x a n d t he G S K C H St u d y Ma n a ger or desi g nee will 
f or war d t his i nf or mati o n t o t he Case 
Ma na ge me nt Gr o u p, Gl o bal Cli nical Safet y a n d 
P har mac o vi gila nce gr o u p mail b o x at G S K (
). Ge nerall y, f oll o w-u p  will 
be n o l o n ger t h a n 6 t o 8 wee ks f oll o wi n g t he esti mate d deli ver y d ate. A n y ter mi nati o n of t h e 
pre g na nc y will be re p ort e d.  
2 1 3 0 5 9 | Pr ot oc ol Cli nical Pr ot oc ol 1 0 Mar 2 0 2 0 | T M F- 1 8 4 3 3 3 | 1. 0
P P D
P P D
P P D

GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 213059  
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SOP-208661 Clinical Protocol Template v5.0 
Page 46 of 56 
While pregnancy itself is not considered to be an AE, abnormal pregnancy outcomes (e.g. 
spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are, and 
should be recorded as an SAE. 
Any female subject who becomes pregnant while participating will discontinue study 
treatment and be withdrawn from the study.   
11 
DATA MANAGEMENT 
As used in this protocol, the term CRF is understood to refer to either a paper form or an 
electronic data record or both, depending on the data collection method.  
For this study, subject data will be entered into an electronic CRF (eCRF), using a validated 
system. Data relating to SAEs, pregnancy and incidents will also be collected on paper forms. 
The investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the CRF. 
The source documents (e.g. hospital records, clinical and office charts, laboratory notes, 
memoranda, subject diaries, questionnaires, 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.  The CRF and paper Diary 
Card can be used as a source document at the discretion of data management. 
Each subject will be assigned and identified by a unique Screening Subject Number. Any 
reference made to an individual subject within the study must be done using their unique 
Screening Subject Number. 
11.1 
Case Report Form 
A CRF is a printed, optical, or electronic document designed to record the protocol required 
information to be reported to the sponsor on each trial subject. 
For each subject who has given informed consent/assent the CRF must be completed and 
signed by the Principal Investigator (or authorized designee) to certify that the data are 
complete and correct.  The investigator must maintain accurate documentation (source data) 
that supports the information entered in the CRF. 
Management of clinical data will be performed in accordance with Third Party BDM Vendor 
applicable standards and data cleaning procedures with oversight by GSK CH to ensure 
integrity of the data, for example, to remove errors and inconsistencies in the data.  
To protect the privacy of subjects, no Personal Information (PI) (including the subject's name 
or initials or full birth date) is to be recorded in the CRF or as part of the query text. 
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.   
GSK CH will obtain and retain all CRFs and associated study data as applicable at the 
completion of the study.  
213059 | Protocol Clinical Protocol 10 Mar 2020 | TMF-184333 | 1.0

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 1 3 0 5 9  
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H  
S O P -2 0 8 6 6 1 Cli nical Pr ot oc ol Te m plate v 5. 0  
Pa ge 4 7  of 5 6  
1 1. 2  
D at a H a n dli n g  
D oc u me ntati o n of all d ata ma na ge me nt acti vities s h o ul d all o w ste p -b y -ste p retr os p ecti ve 
assess me nt of data q u alit y a n d st u d y p erf or m a nce.  
A n y c h a n ges or c orrecti o ns t o data will be perf or me d i n t he Electr o nic Data Ca pt ure ( E D C) 
S yste m, a n d it will i ncl u de rati o nale f or c h a n ges. T he E D C s yst e m has a n a u dit trail, w hic h 
will pr o vi de a c o m plete rec or d of t h e c ha n ges a n d c orrecti o ns e n d orse d b y t he I n vesti gat or.  
A d verse e v e nts will be c o de d usi n g Me di cal Di cti o nar y f or Re g ulat or y Acti vities ( Me d D R A) 
a n d a n y c o n c o mita nt me dicati o ns ter ms (if a p plica ble) usi n g a n i nter nal v ali date d me dicati o n 
dicti o nar y,  
.   
1 1. 2. 1  
D at a Q u eri e s  
Pr o gra m me d e dit c hec ks wil l be ge n erat e d a ut o maticall y, as t he data are bei n g e ntere d i nt o 
t he s yste m. Re p orts a n d listi n gs o n t he C R F data will als o be r u n, i n a d diti o n t o t he q ueries 
alrea d y pr o gra m me d a n d ge nerate d b y t he s yste m, t o raise ma n ual q ueries as nee d e d f or site 
clarific ati o n or c orrecti o n. T he Cli nical Dicti o nar y De vel o p me nt a n d Ma n a ge me nt Gr o u p will 
raise q u eries as n ee d e d o n safet y data t o c o de t he ter ms ( A Es a n d Dr u gs or c o nc o mita nt 
me dicati o n) a p pr o priatel y.  
T he st u d y m o nit or will perf or m o n g oi n g re vie w t he of t he  C R Fs i n acc or da n ce wit h t he 
m o nit ori n g pla n, t o c o nfir m t hat data e ntere d i nt o t he C R F b y a ut h orize d site pers o n nel are 
acc urate, c o m plete, a n d verifia ble fr o m s o urce d oc u me nts; t hat t he safet y a n d ri g hts of 
partici pa nts are bei n g pr otecte d; a n d t hat t he st u d y is bei n g c o n d uct e d i n acc or da n ce wit h t he 
c urre ntl y a p pr o ve d pr ot oc ol a n d a n y ot her st u d y a gree m e nts, I C H G C P, a n d all a p plica bl e 
re g ulat or y re q uire me nts. 
A n y q u eries will be ge nerate d i n t he E D C S yste m t o t he I n vesti gat or or desi g nee, e na bli n g t he 
err ors t o be a d dress e d i n parallel wit h Data Ma n a ge m e nt re vie w. T h e st u d y m o nit or ca n als o 
r u n re p orts a n d listi n gs o n t he C R Fs, t o raise ma n ual q ueries as nee d e d f or site clarificati o n or 
c orrecti o n.  
1 1. 3  
Pr o c e s si n g P ati e nt R e p ort e d O ut c o m e s  
Pa per bas e d patie nt  re p orte d o utc o me ( P R O) data 
ma y be c ollect e d fr o m a diar y, 
q uesti o n naire , or ot her s pecifie d d o c u me nt, etc. a n d e ntere d i nt o t he data ma na ge me nt s yste m 
( D M S).   
All p a per-base d patie nt re p orte d o utc o me P R O s o urce data s h o ul d be re vie we d b y t he st u d y 
staff a n d t he st u d y m o nit or t o e ns ure acc urate tra nscri pti o n of data a n d t hat a n y p ote ntial A Es 
or c o nc o mita nt me dicati o ns re p orte d o n t hese d o c u me nts are disc uss e d wit h t he s u bject a n d 
tra nscri be d acc uratel y t o t he C R F.   
P R Os t hat are class e d as s o urce data w ill be ret ai ne d b y t h e i n vesti gat or a n d tr ue/certifie d 
c o pies ma y be se nt t o a d esi g nat e d ve n d or or G S K C H as re q uire d.  
T o pr otect t he pri vac y of s u bjects, n o Pers o nal I nf or mati o n ( PI) (i ncl u di n g t he s u bject's n a me 
or i nitials or birt h date) is t o be rec or de d o n a n y P R O t hat will be f or war de d t o G S K C H or 
T hir d -Part y Ve n d or.  
I n t his st u d y s u bjects will be pr o vi de d wit h a diar y car d t o c o m plete d uri n g t h e h o me us e 
peri o d, f oll o wi n g first s u per vise d pr o d u ct use a n d diar y c o m pleti o n.  
S u bject self -assess me nt r es p o nses will be c ollecte d directl y i n t he C R F.  
2 1 3 0 5 9 | Pr ot oc ol Cli nical Pr ot oc ol 1 0 Mar 2 0 2 0 | T M F- 1 8 4 3 3 3 | 1. 0
C CI

GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 213059  
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SOP-208661 Clinical Protocol Template v5.0 
Page 48 of 56 
12 
STATISTICAL CONSIDERATIONS AND DATA ANALYSES 
12.1 
Sample Size Determination 
The sample size for this study has been selected based on clinical considerations and to ensure 
compliance with the Agência Nacional de Vigilância Sanitária (ANVISA) Guideline for the 
Safety Evaluation of Cosmetic Products (ANVISA, 2012) which mandates an investigational 
product be tested on at least 30 subjects. 
A sufficient number of subjects will be screened (approximately 350) to randomize 
approximately 150 subjects to ensure that at least 135 subjects (45 per arm) complete the 
study.  
It is deemed that 45 subjects per arm are considered sufficient to assess the primary endpoint 
of the dermatologist assessment of signs and symptoms of cutaneous irritation total score. 
With 45 subjects completing each treatment arm and under an assumption of 4% incidence of 
clinically evaluated intolerance, each group has a 96.68% probability of observing less than 
10% events in the study.  All the groups are independent hence the probability that all three 
groups individually result in less than 10% events is 0.96683. Which equates to 0.9037, or a 
power of 90.4% that the study will result in all three groups having less than 10% of subjects 
with clinical intolerance. 
12.2 
Populations for Analysis 
The Safety population will comprise all randomized subjects who have at least one 
application of the study product (serum, lotion, or cream). This population will be based on 
the product the subject actually received. 
All assessments of safety (i.e. all primary and secondary endpoints) will be based on the 
safety population.  
12.3 
Statistical Analyses 
Additional details of the proposed statistical analysis will be documented in the statistical 
reporting and analysis plan (RAP), which will be written following finalization of the protocol 
and prior to study unblinding/analysis (as appropriate). This section is a summary of the 
planned statistical analyses of the most important endpoints including primary and key 
secondary endpoints. 
12.3.1 
Primary Analysis(es)  
The primary endpoint within each group will be the proportion (number and percentage) of 
subjects determined by a dermatologist to have a clinically relevant positive outcome for 
cutaneous irritation after 21 (+2) days of product use, which is defined as an increase in total 
cutaneous irritation score versus baseline and dermatologist characterization as a clinically-
relevant positive outcome at Visit 3 (Final Visit). 
This is a non-comparative study and the three, separate, within group assessments will form 
the primary analysis. No comparison between groups will be made. No formal statistical 
inference will be performed. 
The primary analysis will be performed using the Safety population. 
In addition, the individual attribute responses and the total score will be listed for each subject 
by visit and by treatment group. 
213059 | Protocol Clinical Protocol 10 Mar 2020 | TMF-184333 | 1.0

GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 213059  
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SOP-208661 Clinical Protocol Template v5.0 
Page 49 of 56 
12.3.2 
Secondary Analysis(es) 
The key secondary endpoint will be the proportion (number and percentage) of subjects 
determined by an ophthalmologist to have a clinically relevant positive outcome for ocular 
irritation after 21 (+2) days of product use, which is defined as an increase in total ocular 
irritation score versus baseline and ophthalmologist characterisation as a clinically-relevant 
positive outcome at Visit 3 (Final Visit).  
No formal statistical inference will be performed. 
In addition, the individual attribute responses and the total score will be listed for each subject 
by visit and by treatment group. 
Further secondary endpoints are change from baseline (prior to any product application) in the 
total subject self-assessment scores for signs and symptoms of cutaneous irritation and ocular 
irritation at 1-2 hours following first product application and 21 (+2) days of twice daily 
product use. The individual attribute responses and the total score will be listed for each 
subject by visit and by treatment group. 
All secondary analyses will be performed using the Safety population. 
12.3.3 
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. 
12.3.4 
Other Analysis(es) 
No other analyses will be performed for this study.  
12.3.5 
Exclusion of Data from Analysis  
Exclusion of any data from the analyses will be determined during a Blind Data Review 
(BDR) Meeting prior to database lock. Any reasons for exclusion from an analysis population 
will be listed, if applicable.  
12.3.6 
Demographic and Baseline Characteristics 
Age will be summarized using descriptive statistics such as means, medians and standard 
deviations. Race and Fitzpatrick skin type will be summarized using frequency counts and 
percentages for the safety population. 
12.3.7 
Study Product Compliance and Use of Other Therapies 
Compliance to each of the study products use will be tabulated and summarized for the safety 
population. Expected compliance is twice daily application for a total of 21 (+2) days. 
12.3.7.1 Prior and Concomitant Medications 
Prior medications, concomitant medications and significant non-drug therapies taken during 
treatment will be listed for the safety population.  
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12.3.8 
Handling of Dropouts and Missing Data  
Missing data will not be replaced or imputed. Dropouts will be included in analyses up to the 
last assessments at the point of discontinuation. 
12.3.9 
Interim Analysis  
No interim analysis is planned for this study 
13 
STUDY GOVERNANCE CONSIDERATIONS 
13.1 
Quality Control  
In accordance with applicable regulations including GCP, and GSK CH procedures, GSK CH 
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 CH requirements. 
When reviewing data collection procedures, the discussion will include identification, 
agreement and documentation of data items for which the CRF will serve as the source 
document. 
GSK CH or designee will monitor the study and site activity to verify that the: 
 Data are authentic, accurate, and complete. 
 Safety and rights of subjects are being protected. 
 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 
GSK CH. 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. 
13.2 
Quality Assurance 
To ensure compliance with GCP and all applicable regulatory requirements, GSK CH may 
conduct a quality assurance assessment and/or audit of the site records, and the regulatory 
agencies may conduct a regulatory inspection at any time during or after completion of the 
study.  
In the event of an assessment, audit or inspection, the investigator (and institution) must agree 
to grant the advisor(s), auditor(s) and inspector(s) direct access to all relevant documents and 
to allocate their time and the time of their staff to discuss the conduct of the study, any 
findings/relevant issues and to implement any corrective and/or preventative actions to 
address any findings/issues identified. 
The investigator(s) will notify GSK CH or its agents immediately of any regulatory inspection 
notification in relation to the study. Furthermore, the investigator will cooperate with GSK 
CH or its agents to prepare the study site for the inspection and will allow GSK CH or its 
agent, whenever feasible, to be present during the inspection. The investigator will promptly 
apply copies of the inspection finding to GSK CH or its agent. Before response submission to 
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the regulatory authority, the investigator will provide GSK CH or its agents with an 
opportunity to review and comment on responses to any such findings.  
The sponsor will be available to help investigators prepare for an inspection. 
13.3 
Regulatory and Ethical Considerations 
13.3.1 
Institutional Review Board/ Ethics Committee  
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, safety statement (including any updates) 
and other relevant documents, e.g. recruitment advertisements, if applicable, from the EC.  All 
correspondence with the EC should be retained in the investigator file.  Copies of EC 
approvals should be forwarded to GSK CH prior to the initiation of the study, and also when 
subsequent amendments to the protocol are made. 
The only circumstance in which an amendment may be initiated prior to EC approval is where 
the change is necessary to eliminate apparent immediate hazards to the subjects.  In that event, 
the investigator must notify the EC and GSK CH in writing immediately after the 
implementation. 
13.3.2 
Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol and legal and regulatory 
requirements, as well as the general principles set forth in the International Ethical Guidelines 
for Biomedical Research Involving Human Subjects (Council for International Organizations 
of Medical Sciences 2002), International Ethical Guidelines for Health-Related Research 
Involving Humans (Council for International Organizations of Medical Sciences, 2016), 
guidelines for GCP (ICH 1996 and revision 2), and the Declaration of Helsinki (World 
Medical Association 2013).  
In addition, the study will be conducted in accordance with the protocol, the ICH guideline on 
GCP, and applicable local regulatory requirements and laws. 
13.3.3 
Subject Information and Consent 
All parties will ensure protection of subject personal data and will not include subject names 
or other identifiable data in any reports, publications, or other disclosures, except where 
required by laws.  
When study data are compiled for transfer to GSK CH and other authorized parties, subject 
names, addresses, and other identifiable data will be replaced by numerical codes based on a 
numbering system provided by GSK CH in order to de-identify study subjects.     
The study site will maintain a confidential list of subjects who participated in the study, 
linking each subject’s numerical code to his or her actual identity.  In case of data transfer, 
GSK CH will maintain high standards of confidentiality and protection of subjects’ personal 
data consistent with applicable privacy laws. 
The informed consent documents must be in compliance with ICH GCP, local regulatory 
requirements, and legal requirements, including applicable privacy laws. 
The informed documents used during the informed consent process must be reviewed and 
approved by the sponsor, approved by the EC before use, and available for inspection. 
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The investigator must ensure that each study subject, is fully informed about the nature and 
objectives of the study and possible risks associated with participation.  
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each before any study-specific activity is performed.  The investigator will 
retain the original of each subject's signed informed consent document. 
13.3.4 
Subject Recruitment  
Advertisements approved by ECs and investigator databases may be used as recruitment 
procedures.  Use of ethics committee approved, generic, prescreening questionnaire to assess 
basic subject characteristics to determine general eligibility for this study is allowed.  This 
generic questionnaire may be used by sites as a phone script and/or to review internal 
databases to identify subjects.   
GSK CH will have an opportunity to review and approve the content of any study recruitment 
materials directed to potential study subjects before such materials are used.  
13.3.5 
Reporting of Safety Issues and Serious Breaches of the Protocol or 
ICH GCP  
Within GSK CH a serious breach is defined as a breach likely to affect to a significant degree 
the safety and rights of a subject or the reliability and robustness of the data generated in GSK 
CH-sponsored human subject research studies.  
In the event of any prohibition or restriction imposed (i.e., clinical hold) by an applicable 
competent authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, GSK CH should be informed immediately.  
In addition, the investigator will inform GSK CH immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and of 
any serious breaches of this protocol or of ICH GCP that the investigator becomes aware of. 
13.4 
Posting of Information on Publicly Available Clinical Trial 
Registers 
Study information from this protocol will be posted on publicly available clinical trial 
registers before enrollment of subjects begins in accordance with applicable GSK CH 
processes. 
GSK intends to make anonymized subject-level data from this trial available to external 
researchers for scientific analyses or to conduct further research that can help advance medical 
science or improve patient care. This helps ensure the data provided by trial participants are 
used to maximum effect in the creation of knowledge and understanding 
13.5 
Provision of Study Results to Investigators 
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 CH site or other mutually-
agreeable location. 
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GSK CH will also provide the investigator with the full summary of the study results.  The 
investigator is encouraged to share the summary results with the study subjects, as 
appropriate. 
The procedures and timing for public disclosure of the results summary and for development 
of a manuscript for publication will be in accordance with GSK CH Policy. 
A manuscript will be progressed for publication in the scientific literature if the results 
provide important scientific or medical knowledge. 
13.6 
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 CH audit or regulatory inspection) and must be available for 
review in conjunction with assessment of the facility, supporting systems, and relevant site 
staff. 
Where permitted by local laws/regulations or institutional policy, some or all of these records 
can be maintained in a format other than hard copy (e.g. microfiche, scanned, electronic); 
however, caution needs to be exercised before such action is taken.  
The investigator must ensure that all reproductions are legible and are a true and accurate 
copy of the original and meet accessibility and retrieval standards, including re-generating a 
hard copy, if required.  Furthermore, the investigator must ensure there is an acceptable back-
up of these reproductions and that an acceptable quality control process exists for making 
these reproductions. 
The investigator must assure that the subject’s anonymity will be maintained.  On CRFs or 
other documents submitted to GSK CH, 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 GSK CH, e.g. subjects’ 
written consent forms, should be maintained by the investigator in strict confidence. 
Records and documents, including signed ICF, pertaining to the conduct of this study must be 
retained by the investigator as per the signed contractual agreement, from the issue of the final 
Clinical Study Report (CSR) or equivalent summary, unless local regulations or institutional 
policies require a longer retention period. The minimum retention time will meet the strictest 
standard applicable to that site for the study, as dictated by any institutional requirements or 
local laws or regulations, GSK CH standards/procedures, and/or institutional requirements.   
No study document should be destroyed without a prior written agreement between GSK CH 
and the investigator. The investigator must notify GSK CH 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. 
13.7 
Conditions for Terminating the Study  
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the EC, or study product safety problems, or at the discretion of GSK 
CH.  In addition, GSK CH retains the right to discontinue development of developmental 
cosmetic facial products at any time.  
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If a study is prematurely terminated, GSK CH will promptly notify the investigator.  After 
notification, the investigator must promptly contact all participating subjects and should 
assure appropriate therapy/ follow-up for the subjects.  As directed by GSK CH, all study 
materials must be collected and all CRF’s completed to the greatest extent possible. Where 
required by the applicable regulatory requirements, GSK CH should inform the regulatory 
authority(ies) and the investigator should promptly inform the EC and provide the EC a 
detailed written explanation of the termination or suspension.  
If the EC terminates or suspends its approval/favorable opinion of a trial, the investigator 
should promptly notify the GSK CH and provide GSK CH with a detailed written explanation 
of the termination or suspension. 
Upon completion or premature discontinuation of the study, the GSK CH monitor will 
conduct site closure activities with the investigator or site staff, as appropriate, in accordance 
with applicable regulations including GCP, and GSK CH Standard Operating Procedures. 
14 
REFERENCES 
1. ANVISA, Guideline for the Safety Evaluation of Cosmetics Products, 2012  
2. ANVISA; Resolution 79/00, Annex XXI and its updates 
3. Berardesca E, Farage M, Maibach H. Sensitive skin: an overview. Int J Cosmet Sci.2013 
Feb;35(1):2-8. 
4. Christensen M, Kligman AMJJotSoCC. An improved procedure for conducting lactic acid 
stinging tests on facial skin. 1996;47(1):1-12. 
5. COSMETICS EUROPE: Guidelines for the Safety Assessment of a Cosmetic Product, 
2004. 
6. De Groot AC, White IR, Flyvholm MA, et al. Formaldehyde‐releasers in cosmetics: 
Relationship to formaldehyde contact allergy: Part 1. Characterization, frequency and 
relevance of sensitization, and frequency of use in cosmetics. 2010;62(1):2-17. 
7. Edward MJ, Norman FMTR. The controlled use test in a cosmetic product safety 
substantiation program. Journal of Toxicology: Cutaneous and Ocular Toxicology. 
1982;1(2):117-32. doi: 10.3109/15569528209051517 
8. European Commission (EC), Regulation No. 1223/2009 
9. Farage MA, Katsarou A, Maibach HIJCd. Sensory, clinical and physiological factors in 
sensitive skin: A review. 2006;55(1):1-14. 
10. 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. 
11. ICH Topic E6 (R2) Guideline for Good Clinical Practice, Nov 2016. 
12. Lundov MD, Johansen JD, Carlsen BC, et al. Formaldehyde exposure and patterns of 
concomitant 
contact 
allergy 
to 
formaldehyde 
and 
formaldehyde‐releasers. 
2010;63(1):31-6. 
13. National Health Surveillance Agency Brazil (ANVISA). Guideline for the Safety 
Evaluation of Cosmetic Products. Brasília; 2012. 
14. World Medical Association Declaration of Helsinki, 59th General Assembly, Seoul 2008. 
15. World Medical Association Declaration of Helsinki, 64th General Assembly, Fortaleza 
2013 
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15 
APPENDICIES 
15.1 
APPENDIX 1 - ABBREVIATIONS 
The following is a list of abbreviations that may be used in the protocol. 
Table 15-1 
Abbreviations 
Abbreviation 
Term 
AE 
adverse event 
ANVISA 
Agência Nacional de Vigilância Sanitária 
BDM 
Biostatistics and data management 
CRF 
case report form 
CSA 
clinical study agreement 
DMS 
Data Management Services 
EC 
ethics committee 
EC 
European Commission 
eCRF 
Electronic Case Report Form 
EDC 
Electronic data capture 
FSFV 
First subject first visit 
GCP 
Good Clinical Practice 
GSKCH 
GlaxoSmithKline Consumer Healthcare 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
ID 
identification 
IEC 
Independent Ethics Committee 
IRC 
internal review committee 
IRT 
Interactive Response Technology 
LAST 
Lactic acid sting test 
LSLV 
last subject last visit  
M 
Molar 
MedDRA 
medical Dictionary for Regulatory Activities 
MQP 
Medically qualified person 
NSAID 
Non-steroidal anti-inflammatory drug 
PI 
principal investigator 
PI 
Personal information 
PRO 
Patient Reported Outcomes 
QC 
quality control 
RAP 
Reporting and analysis plan 
SAE 
serious adverse event 
SRSD 
single reference study document 
SS 
safety statement 
UK 
United Kingdom 
UV 
Ultraviolet 
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15.2 
APPENDIX 2 – FITZPATRICK SKIN TYPE GRADING 
The Fitzpatrick skin type scale is a numerical classification that is widely used by 
dermatologists to classify a person’s skin type by their response to sun exposure (Fitzpatrick, 
1988).  
Table 15-2 
FITZPATRICK SKIN TYPE GRADING 
Skin Type 
Sunburn and Tanning History 
I 
Always burns easily; never tans (pale white skin) 
II 
Always burns easily; tans minimally (white skin) 
III 
Burns moderately; tans gradually (light brown skin) 
IV 
Burns minimally, always tans well (moderate brown skin) 
V 
Rarely burns, tans profusely (dark brown skin) 
VI 
Never burns (deeply pigmented dark brown to black skin) 
 
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Si g nat ure Pa ge f or  2 1 3 0 5 9 T M F- 1 8 4 3 3 3 v 1. 0
Si g nat ure Pa ge f or T M F- 1 8 4 3 3 3 v 1. 0
Reas o n f or si g ni n g: A p pr o ve d
Na me: 
R ole: A
Date of si g nat ure: 0 5- Mar- 2 0 2 0 1 1: 2 2: 2 1
G M T + 0 0 0 0
Reas o n f or si g ni n g: A p pr o ve d
Na me: 
R ole: A
Date of si g nat ure: 0 6- Mar- 2 0 2 0 1 5: 3 1: 2 3
G M T + 0 0 0 0
Reas o n f or si g ni n g: A p pr o ve d
Na me: 
R ole: A
Date of si g nat ure: 1 0- Mar- 2 0 2 0 1 1: 3 8: 3 9
G M T + 0 0 0 0
2 1 3 0 5 9 | Pr ot oc ol Cli nical Pr ot oc ol 1 0 Mar 2 0 2 0 | T M F- 1 8 4 3 3 3 | 1. 0
P P D
P P D
P P D