A Human Subject 24 Hour Patch Test to Assess the Irritation Potential of Four Skin Serum Products
Phase: NA
Conditions: Skin Care
Sponsor: GlaxoSmithKline

Clinical Protocol
207235
 
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CONFIDENTIAL
SUMMARY INFORMATION
Title:
A Human Subject 24 Hour Patch Test to Assess the 
Irritation Potential of Four Skin SerumProducts
Protocol Number:
207235
Sponsor:
GlaxoSmithKline Consumer Healthcare (GSKCH)
Rua Hungria, 1240 4º andar, Jardim Europa
São Paulo/SP –Brazil, CEP 01455-000
Tel: 
Product Name:
Experimental Daily DefenseSerum
Development Phase:
N/A
Expert Advice Outside of Normal 
Working Hours:
Tel: 
 (US)
Key Protocol Authors:
PRIMARY CONTACT
Clinical Research Scientist:
, MSc
GlaxoSmithKline Consumer Healthcare (GSKCH)
St. Georges Avenue, Weybridge, Surrey, 
KT13 0DE. UK
Tel. 
PRIMARY CONTACT
Clinical Study Manager:
GlaxoSmithKline Consumer Healthcare (GSKCH)
Rua Hungria, 1240 4º andar, Jardim Europa
São Paulo/SP –Brazil, CEP 01455-000
Tel:
Biostatistician:
Other Protocol Authors:
Clinical Supplies:
Data Manager:
Medical Expert:
, MD, Ph.D 
Principal Investigator:
Regina M. Doi -Dermatologist
Study Site Name & Address:
AZIDUS BRASIL PESQUISA CIENTÍFICA E 
DESENVOLVIMENTO LTDA.
Rua: General Osório, n° 507 -Bairro: Vila 
 
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Martina -Valinhos –São Paulo –Brazil.
Study Site Telephone 
Number:
 
Study Examiner(s):
Patch assessors will be assigned according to the 
site schedule (before First Subject First Visit) and 
documented in the site file.
 
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PRINCIPAL INVESTIGATOR PROTOCOL AGREEMENT 
PAGE
I confirm agreement to conduct the study in compliance with the protocol and any 
amendments and according to the current International Conference on Harmonization 
of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)
Good Clinical Practice (GCP)guidelines.
I acknowledge that I am responsible for overall study conduct. I agree to personally 
conduct or supervise the described study.
I agree to ensure that all associates, colleagues and employees assisting in the conduct 
of the study are informed about their obligations. Mechanisms are in place to ensure 
site staff receives all appropriate information throughout the study.
I agree to conduct this study in full conformance with the laws and regulations of the 
country in which the research is conducted.
Investigator Name:
Investigator Qualifications:
Investigator Signature:
Date of Signature/ Agreement:
DD/MMM/YYYY
 
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Table of Content
SUMMARY INFORMATION...............................................2
PRINCIPAL INVESTIGATOR PROTOCOL AGREEMENT 
PAGE..............................................................................4
Table of Content......................................................................5
PROCESS FOR AMENDING THE PROTOCOL...............9
PROTOCOL AMENDMENT PAGE....................................10
PROTOCOL SYNOPSIS FOR STUDY 207235...................13
1. INTRODUCTION...............................................................16
2. OBJECTIVE(S) AND ENDPOINT(S)...............................17
3. STUDY PLAN.....................................................................17
3.1. Study Design.......................................................................17
3.2. Subject Restrictions...........................................................18
3.3. Type and Planned Number of Subjects............................19
3.4. Dose Justification...............................................................19
4. SELECTION OF STUDY POPULATION AND 
WITHDRAWAL CRITERIA........................................19
4.1. Inclusion Criteria...............................................................20
4.2. Exclusion Criteria..............................................................20
4.3. Screening/ BaselineFailures..............................................22
4.4. Withdrawal/ Stopping Criteria.........................................23
4.5. Subject Replacement..........................................................23
4.6. Subject and Study Completion..........................................23
5. PRODUCT INFORMATION.............................................24
5.1. Study Product.....................................................................24
 
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5.2. Dose Schedule.....................................................................24
5.3. Overdose.............................................................................25
5.4. Product Assignment...........................................................25
5.4.1 Randomization...................................................................25
5.4.2 Blinding...............................................................................25
5.4.3 Code Breaks........................................................................26
5.5. Packaging and Labelling...................................................26
5.5.1. Accountability of Product.................................................26
5.5.2. Storage of Product............................................................27
6.1. Visit 1 -Screening Visit......................................................27
6.1.1 Telephone Screening..........................................................27
6.1.2 Informed Consent..............................................................27
6.1.3 Demographics.....................................................................28
6.1.4 Medical History and Concomitant Medication................28
6.2 Visit 2 (Day 1), Visit 3 (Day 2) and Visit 4 (Day 3)............28
6.3 Patch Assessments...............................................................29
6.4Visit 5 (Day 4) Study Conclusion.......................................30
7. SAFETY ASSESSMENTS..................................................30
7.1. Definitions of an Adverse Event and Serious Adverse 
Event.................................................................................30
7.1.1. Adverse Events..................................................................30
7.1.2. Serious Adverse Events.....................................................32
7.2. Recording Adverse Events and Serious Adverse Events.33
7.3. Evaluating Adverse Events and Serious Adverse Events33
7.4. Reporting Adverse Events and Serious Adverse Events..35
7.5. Follow-up of Adverse Events and Serious Adverse Events
..........................................................................................36
7.6. Collection ofPregnancy Information................................37
7.6.1. Time Period for Collecting of Pregnancy Information...37
 
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7.6.2. Action to be Taken if Pregnancy Occurs.........................38
8. DATA MANAGEMENT....................................................38
8.1. Source Documents/ Data....................................................38
8.2. Electronic Case Report Form............................................39
8.3. Data Handling....................................................................40
8.3.1. Data Queries......................................................................40
9. STATISTICAL CONSIDERATIONS AND DATA 
ANALYSES....................................................................40
9.1. Sample Size Determination................................................41
9.2. General Considerations.....................................................41
9.2.1. Definition of Analysis Populations...................................41
9.2.2. Exclusion of Data from Analysis......................................41
9.2.3. Criteria for Evaluation.....................................................41
9.2.4. Handling of Dropouts and Missing Data.........................42
9.3. Statistical Methods and Analytical Plan...........................42
9.3.1. Demographic and Baseline Characteristics.....................42
9.3.2. Primary Analysis(es).........................................................42
9.3.3. Secondary Analysis(es).....................................................42
9.3.4. Safety Analysis(es).............................................................42
10.1. Posting of Information on Publicly Available Clinical 
Trials Registers................................................................43
10.2. Regulatory and Ethical Considerations, Including the 
Informed Consent............................................................43
10.3. Quality Control (Study Monitoring)...............................44
10.4. Quality Assurance............................................................44
10.5. Conditions for Terminating the Study............................45
10.6. Records Retention............................................................45
 
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10.7. Provision of Study Results to Investigators, posting of 
Information on Publicly Available Clinical Trials 
Registers and Publication................................................46
11. REFERENCES..................................................................47
12. APPENDICES...................................................................48
12.1. Appendix 1 -Abbreviations and Trademarks................48
12.2. Appendix 2 –Skin Irritation Scoring System.................49
12.3. Appendix 3 -Fitzpatrick Skin Type Grading.................50
 
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PROCESS FOR AMENDING THE PROTOCOL
Protocol modifications to ongoing studies which could potentially adversely affect the 
safety of subjects or which alter the scope of the investigation, the scientific quality of 
the study, the experimental design, dosages, duration of therapy, assessment 
variables, the number of subjects treated, or subject selection criteria are considered 
major/substantial amendments and must be made only afterappropriate consultation 
between an appropriate representative of GSKCH and the investigator.
Details of amendments to the protocols should be recorded on the following page. 
Protocol modifications must be prepared by a representative of GSKCH.  All changes 
must be justified in the Reason for Amendment section of the following Protocol 
Amendment Page. Approval of amendments will be made by the original protocol 
signatories or their appropriate designees.
All major/substantial protocol modifications must be reviewed and approved by the 
appropriate Institutional Review Board (IRB)/Independent Ethics Committee (IEC)in 
accordance with local requirements, before the revised edition can be implemented. 
All non-substantial/ minor/ administrative amendments should be submitted to the 
IRB/ IECas per country specific requirements. In some countries pre-approval of a 
minor amendment is not required and will just be held on file by the sponsor and 
investigator.
 
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PROTOCOL AMENDMENT PAGE
Details of all amendments should be recorded in the table below. Affected sections should be listed in the table; the actual 
amendment/ change should be made in the relevant section of the main protocol. 
To highlight the change, the following features will be used: 
To addtext: Useof CAPITAL LETTERS, BOLD AND UNDERLINE
To delete text: Use of Strikethrough e.g. strikethrough
Amendment 
No. & New 
Protocol 
Version No.
Type of Amendment
Reason for 
Amendment
Other Documents 
Requiring 
Amendment
Section(s) Amended 
PI Amendment 
Agreement
Signature & 
Date
Amendment 
No.:1
Non-Substantial/Minor    
Correction to site 
telephone 
number.
Update to clarify 
recording of 
dermal response 
scores.
Clarify the
wording for 
success criteria.
Informed Consent  
Yes No
Safety Statement     
Yes No
CRF                       
Yes No
Summary 
Information
6.3 Patch 
Assessments 
7.1.1 Events NOT 
meeting definition 
of an AE include:
Summary/Statistical 
methods 
9.2.3. Criteria for 
Evaluation
Signature:
Protocol 
Version 
No.:2.0
Substantial/ Major           
Date:
 
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Amendment 
No.:2
Non-Substantial/Minor    
A new 
formulation code
for oneof the test 
products.
Clarification of 
wording
Informed Consent   
Yes No
Safety Statement     
Yes No
CRF                       
Yes No
Product
Information
5.1 Study Product
5.5 Packaging and 
labelling
4.3 
Screening/Baseline 
Failures
6.1.2 Informed 
Consent
Signature:
Protocol 
Version 
No.:3.0
Substantial/ Major           
Date:
Amendment 
No. & New 
Protocol 
Version No.
Type of Amendment
Reason for 
Amendment
Other Documents 
Requiring 
Amendment
Section(s)Amended 
PI Amendment 
Agreement
Signature & 
Date
Amendment 
No.:
Non-Substantial/Minor    
Informed Consent   
Yes No
Safety Statement     
Yes No
CRF                       
Yes No
Signature:
Protocol 
Version 
No.:
Substantial/ Major           
Date:
Amendment 
No.:
Non-Substantial/Minor    
Informed Consent   
Yes No
Safety Statement     
Yes No
CRF                       
Yes No
Signature:
Protocol 
Version 
No.:
Substantial/ Major           
Date:
 
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SCHEDULE OF EVENTS
Procedures
Visit1
Screen
Visit2
Day1
Visit3
Day2
Visit4
Day3
Visit5
Day4
Informedconsent
X
Demographics
X
Medical History
X
Current/Concomitant Medications
reviewed
X 
X 
X 
X 
X
InclusionandExclusion cri
teria
X
Eligibilitytoparti
cipatedeterminedby
Investigator (dermatologist)
X
Continued eligibility
X 
X 
X 
X
Randomisation
X
Application of patches totestsi
tes
X
Removalofpatchesatstudysite 24 
(± 2hrs) after application
X
Assessment of test sites 15-30 minutes 
following patch removal at study centre
a
X
Assessment of test sites 24 (± 2hrs) 
following patch removal at study centre
a
X
Final assessment of test sites 48 (± 2hrs) 
following patch removal at study centre
a
X
Adverse event assessment
b
X 
X 
X 
X
Study Conclusion
X
a. Atrained (by a dermatologist) blinded evaluator will perform assessmentsof all test sites for symptoms of 
irritation using the scoring system detailed in Appendix 2.
b. Subjects are asked to report any adverse events from Visit 2 (or Visit 1 if patch application occurs at Visit 1) 
and the use of anyconcomitant medicationsthroughout the study.
NOTE: Visit 1 and visit 2 could occur on the same day, but Visit 2 must be within 7 days of Visit 1.
 
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PROTOCOL SYNOPSIS FOR STUDY 207235
Brief Summary
A cosmetic product that is freely available to the consumer must be safe when applied
under normal orreasonably foreseeable conditions of use. For this reason, the raw
materials used in a product formulation must be raw materials with proven safety and
tolerability.As a general requirementthe safety and tolerability of afinal formulation 
must be confirmed before it is marketed.(Guideline for the Safety Evaluation of 
Cosmetic Products; Agência Nacional de Vigilância Sanitária (ANVISA) 2012).
Cutaneous compatibility studies such as patch tests are designed to confirmthe 
absenceofirritation and/or sensitization duringsingle or repeated topicalapplication 
of a cosmetic product to human subjects.
Among the numerous cutaneous methods, patch tests are a well-recognized diagnostic 
tool (Lachapelle, 2012).This methodology involves occlusiveor semi-occlusive
application of test product to the skin, ensuringa higher contact between the 
components of the product formula and the skin. 
The objective of this clinical study is to assess the cutaneous irritation potential of 
four test products under maximized conditions withdermatologistsupervision.
Objective(s) and Endpoint(s)
Objective(s)
Endpoint(s)
Primary
To assess the irritation potential of four 
prototype daily defenseserum
formulations after 24 (± 2)hoursunder 
semi-occlusivepatch application to the 
skin of healthy volunteers
Trained evaluatorassessment of product 
tolerability through visual assessment of 
cutaneous irritation 15-30 minutes, 24 +/-
2 and 48 +/-2 hours after patch removal
Secondary
To evaluate the general safety of four 
prototype daily defenseserum
formulations
Frequency and severity of Adverse 
Events
 
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Study Design
This is an evaluator (single) blind, test site randomized and intra-subject comparison
patch test study to evaluate the cutaneous irritation potential of four experimental 
daily defenseserumformulations, including a saline solution as a negative control.
Subjects will beexposed to 24hour semi-occlusivepatch applications of the test 
products and negative control.
Typeand Planned Number of Subjects
Sufficient subjects will be screened such thatapproximately 40 subjects will be 
randomizedto ensureapproximately30evaluable subjects complete the entire study. 
Diagnosisand Main Criteria for Inclusion
Healthy male and female volunteers aged 18 to 65with no activedermatological 
conditionswill be enrolled into this study. 
Product Information
Test Product 1
Test Product 2 
Test Product 3 Test Product 4
Reference 
Product 1
Product Name 
Experimental 
Daily Defense
SerumA
Experimental 
Daily Defense 
Serum C
Experimental 
Daily Defense 
Serum G
Experimental 
Daily Defense 
Serum N
Saline Solution 
Sodium 
Chloride
(NaCl; 0.9%aq)
Product 
Formulation 
Code (MFC)
N/A
Site to Supply 
Dose
0.02ml/cm2
0.02ml/cm2
0.02ml/cm2
0.02ml/cm2
0.02ml/cm2
Route of 
Administration
Topical 
application via 
semi occlusive 
patch
Topical 
application via 
semi occlusive 
patch
Topical 
application via 
semi occlusive 
patch
Topical 
application via 
semi occlusive 
patch
Topical 
application via 
semi occlusive 
patch
 
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CCI
CCI
CCI
CCI
CCI

Statistical Methods
The primary evaluation will be the irritation scores after patch removal for each of the 
four test formulations. 
The study will be considered a success if no irritation is observedwhich is 
attributable to the test product at any time point, or if any observed irritation 
for the test product is not clinically differentiable from the saline solution
The primary outcome for success is that there will be no evidence of irritation
observed in the test products at any time point attributable to the product.
No formal statistical inference will be performed. Summary statistics will be 
presented by productgroup for skin irritation scores at 15-30 mins, 24 and 48 hours
after patch removal. These will include mean irritation scores(if any subjects have 
reported irritation)and the number and percentage of subjects recording each 
category of skin irritation scores.
Adverse Events (AE) will be tabulated by the sponsor according to the current 
version of the Medical Dictionary for Regulatory Activities (MedDRA). Frequencies 
and percentages will be presented overall, for each system organ class, and for each 
preferred term. Summaries of treatment-emergent AEs, treatment-related AEs, AEs 
leading to discontinuation, and serious AEs willbe completed. For treatment-related 
AEs, these will also be presented by productgroup/test site.
 
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1. INTRODUCTION
In recent years the cosmetic industry has grown considerably, along with its concern 
for the development of safe and effective products.  This heightened industry 
awareness,combined withconsumer and regulatory agency requirements have led 
cosmetic manufacturers to adopt procedures that provide them with a better 
understanding of the safety and compatibility of their products.  This includes the 
conduct of clinical tests to assess the safety and efficacyof products under 
supervision of a dermatologist prior to marketing.
A cosmetic product that is freely available to the consumer must be safe when applied
under normal or reasonablyforeseeable conditions of use (Guidelinefor the Safety 
Evaluationof Cosmetic Products; ANVISA, 2012). The raw materials used in the 
product formulation must be of proven safety withestablished use in the cosmetic 
industry, safety and compatibility of thefinal formulation must also be confirmed 
before it is marketed.
Skin contact with topical products such as cosmetics may trigger different types of 
reactions including eczematous,contact dermatitis, urticaria, acne and spots.  Contact 
dermatitis can arisefrom two mechanisms: primary irritation,through the action of 
irritant substances; or sensitization, in the presence of anallergenic ingredient 
(Birmingham, 1965)
Tests to evaluate the irritation and sensitization potential of a product must take into
account a number of variables including the components used in the formulation 
concentration, absorption, amount applied, skin condition, application directions and
frequency, as well as anycumulative effects (Dooms-Goossens, 1993).
Primary irritation results from a direct chemical attack on the skin and is 
characteristically a rapid response, occurring on first contact with the skin. The effect 
may be limited to the stratum corneumand may result in symptoms such as dryness, 
flaking, or cracking. Primary irritation may involve deeper penetration, through the 
epidermis and into the dermis, where the classic inflammatory response takes place 
with erythema (reddening)and possibly edema(swelling), vesiculation (blistering) or 
exudation (weeping).
The human patch test is a well-established industry test for assessing primary skin 
irritation potential. The products are applied viaan occlusive orsemi-occlusivepatch. 
 
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This occlusion provides a higher contact between the components of the product 
formula and the skin. 
This clinical study is being performed to assess the primary irritation potential of the 
four study products. A standard saline solution will also be included as a negative 
control.
All test products will be applied via semi-occlusivepatches onto the dorsum (scapular 
region)skin of healthy subjects for a 24 hour period.Subjects will leave the patches 
in place until they return to the site where the patches will be removed and the skin 
assessed for any signs of irritation.Visual evaluations of dermal irritancy will be 
performed by (where ever possible) the sametrained assessor 15 to 30 minutes after 
patch removal, and again at24 (± 2) and 48 (± 2) hours after the patch removal. The 
scores will be analyzed to establish the irritationpotential of each test product.
2. OBJECTIVE(S) AND ENDPOINT(S)
Objective(s)
Endpoint(s)
Primary
To assess the irritation potential of four 
prototype daily defenseserum
formulations after 24 (± 2) hours under 
semi-occlusivepatch application to the 
skin of healthyvolunteers
Trained evaluatorassessment of product 
tolerability through visual assessment of 
cutaneous irritation 15-30 minutes, 24 +/-
2 and 48 +/-2 hours after patch removal
Secondary
To evaluate the general safety of four 
prototype daily defenseserum
formulations
Frequency and severity of Adverse 
Events
3. STUDY PLAN
3.1. Study Design
This is an evaluator (single) blind, singlesite,randomized and intra-subject 
comparisonpatch test study to evaluate the cutaneous irritation potential of four 
experimental daily defenseserumformulations, including a saline solution as a 
negative control.
Subjects will beexposed to 24hour semi-occlusivepatch applications of the test 
products and negative control. At all study visits, subjectswill be asked by a trained 
 
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technician if there have been any feelings of discomfort since the last visit, and also if 
any medication has been taken during this period.
3.2. Subject Restrictions
Lifestyle/ Dietary
During the entire study (Screening –Last Subject Last Visit (LSLV) the following 
should be avoided:
1. Applyingany other product to the test site.
2. Changingany cosmetic habits, including personal hygiene.
3. Changingdietaryhabits.
4. Getting the patch test site wet: during showers or bathing,in pools or 
lakes/ocean, sauna (study site to provide instructions on how to 
shower/bathe throughout the study).
5. Activities that cause excessive sweating.
6. Removingthe patches.
7. Wearingtight or restrictive clothingthat can remove the patch through 
friction or cause redness.
8. Exposureto excessive prolonged sunlight and not to undergoartificial 
tanningor use tanning beds
9. Introducing new products during the study including soap, laundry 
detergent, or fabric softener.
Medications and Treatments
During the entire study (Screening –LSLV) the following medications and treatments 
should be avoided:
1. Subjects will be instructed to avoid cosmetics, moisturizers, and other 
topical product application on the dorsum (back)area for the duration of 
their time in the study.
2. Having any body aesthetic or dermatological treatments performed.
3. Changinghormone treatment.
4. Changingcontraceptive method.
5. Subjects will be instructed tonot use the following medications:
a) Systemic or topicalcorticosteroids
b) Systemic or topical immunosuppressive drugs
c) Systemic or topical antihistamines
d) Vitamin A acid and its derivatives
e) Non-steroidal anti-inflammatory drugs 
6. Concomitant topical treatment at test sites
 
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3.3. Type and Planned Number of Subjects
Healthy male and female volunteers aged 18 to 65with no dermatological disorders 
will be enrolled into this study. Subjects with a Fitzpatrick phototype I to IV 
(Appendix 3) will be recruited to ensure any reactions are clearly visible on subject’s 
skin. A sufficient number of subjects will be screened such that approximately 40 
subjects will be randomizedto ensure at least 30evaluable subjectscompletethe 
study. 
The sample size has been selected to provide descriptive information on the 
tolerability and safety of the products.
Subjects will be recruited from the site’sdatabase.
3.4. Dose Justification
The prerequisite for a patch test is the requirement that the whole test siteis covered 
with the test product, without spreading or overlapping into other test sites. Previous 
work (Isaksson, 2007) has shown that the optimal dose to fulfil these requirements is 
0.02ml/cm2.
This is a single-dose study;subjects will have a semi-occlusive patch (adhesive tape) 
measuring65cm
2, containingpaper discs of 1.2cm
2 onto which 0.02ml/cm2(Lee, 
2007) each of the four experimental daily defenseserumformulationsand negative 
control;saline solution (sodium chloride (NaCl
aq) 0.9%) will be applied by trained 
personnel,once, according to the randomisation schedule for 24 (± 2) hours on the 
dorsum (scapular) region.
4. SELECTION OF STUDY POPULATION AND 
WITHDRAWAL CRITERIA
Specific information regarding warnings, precautions, contraindications, adverse 
events, and other pertinent information on the GSK investigational product or other 
study treatment that may impact subject eligibility is provided in the Safety 
Statement.
Deviations from inclusion and exclusion criteria are not allowed because they can 
potentially jeopardize the scientific integrity of the study, regulatory acceptability or 
subject safety. Therefore, adherence to the criteria as specified in the protocol is 
essential.
 
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4.1. Inclusion Criteria
A subject will be eligible for inclusion in this study only if all of the following criteria 
apply:
1. CONSENT
Demonstrates understanding of the study procedures, restrictions and willingness to 
participate as evidenced by voluntary written informed consent and has received a 
signed and dated copy of the informed consent form. 
2. AGE
Aged between 18 and 65years inclusive.
3. GENERAL HEALTH
a.)Good general and mental health with, in the opinion of the investigator or 
medically qualified designee no clinically significant and relevant 
abnormalities in medical history or upon physical examination.
b.)Subjects must have intact skin on the proposed application site; dorsum 
(scapularregion).
4. Skin Type
Fitzpatrick phototype I to IV 
5. COMPLIANCE
Agreement to comply with the procedures and requirements of the study andto attend 
the scheduled assessmentvisits.
4.2. Exclusion Criteria
A subject will not be eligible for inclusion in this study if any of the following criteria 
apply:
1. PREGNANCY
Women who are known to be pregnant or who are intending to become pregnant over 
the duration of the study.
2. BREAST-FEEDING
Women who are breast-feeding
 
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3. CONCURRENT MEDICATION/MEDICAL HISTORY
a. Any history of significant dermatological diseases or conditions or medical 
conditions known to alter skin appearance or physiologic response (e.g. 
diabetes,) which could, in the opinion of the Investigator, preclude topical 
applicationof the investigational products and/or interfere with the evaluation 
of the test site reaction. 
b. Presence of open sores, pimples, or cysts at the application site. 
c. Active dermatosis (local or disseminated) that might interfere with the results 
of the study.
d. Considered immune compromised. 
e. History of diseases aggravated or triggered by
 ultraviolet radiation.
f. Participants with dermatographism.
g. Currently using any medication which in the opinion of the investigator, may 
affect the evaluation of the study product, or place the subject at undue risk.
h. Use of the following topical or systemic medications: immunosuppressants, 
antihistamines, non-hormonal anti-inflammatory drugs, and corticosteroids up 
to 2 weeks before screening visit.
i. Oral or topical treatment with vitamin A acid and/or its derivatives up to 1 
month before the screening visit.
j. Intention of being vaccinated during the study period or vaccination within 3 
weeks of the screening visit.
k. Currently receiving allergy injections, or due to receive an injection within 7 
days prior to Visit1, or expects to begin injections during study participation
4. ALLERGY/ INTOLERANCE
a. Previous history of atopy, allergic reactions, irritation or intense discomfort 
feelings to topical-use products, cosmetics or medication.
b. Known or suspected intolerance or hypersensitivity to any of thestudy 
materials (orclosely related compounds) or any of their statedingredients, 
 
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including any component of the patches.
c. History of sensitization in a previous patch study.
5. CLINICAL STUDY/ EXPERMENTAL PRODUCT
a. Participation in another clinical study (including cosmetic studies) or receipt 
of an investigational drug within 30days of the screening visit.
b. Previous participation in this study.
6. SUBSTANCE ABUSE
      a. Recenthistory (within the last5years) of alcohol or other substance abuse.
7. DIAGNOSTIC ASSESSMENTS AND OTHER CRITERIA
a. Intense sunlight exposure or sun tanning sessions up to 30days before the 
Screening evaluation.
b. Intention of bathing, sauna, water sports,or activitiesthat leadto intense 
sweating.
c. Any Subject who, in the judgment of the Investigator, should not participate in 
the study.
d. Any skin marks on the test site that might interfere with the evaluation of 
possible skin reactions (e.g. pigmentation disorders, vascular malformations, 
scars, tattoos, excessive hair, numerous freckles).
e. Prisoner or involuntary incarcerated subject.
f. Subject from an indigenous tribe.
8. PERSONNEL
An employee of the sponsor or the study site or members of their immediate family.
4.3. Screening/ Baseline Failures
Screen failures are defined as subjects who consent to participate in the study but are 
never subsequently randomized.  In order to ensure transparent reporting of screen 
failure subjects, a minimal set of screen failure information is required including 
Demography, Screen Failure details, Eligibility Criteria, and any Serious Adverse 
 
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Events. Re-screening of subjects CONSIDERED PREVIOUS SCREEN 
FAILURESwill not be allowed in this study.
4.4. Withdrawal/ Stopping Criteria
A subject may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioralor 
administrative reasons.
If the reason for removal of a subject from the study is an AE or an abnormal 
laboratory test result, the principal specific event or test will be recorded on the 
electronic case report form (CRF).  If a subject is withdrawn from the study because 
of a product limiting AE, thorough efforts should be clearly made to document the 
outcome. Any AEs ongoing at the final visit will be followed up until resolved, the 
condition stabilizes, is otherwise explained, or the subject is lost to follow-up.
The following actions must be taken in relation to a subject whofails to attend the 
clinic for a required study visit:
a) The site must attempt to contact the subject and re-schedule the missed visit as 
soon as possible. 
b) The site must counsel the subject on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the subject wishes to 
and/or should continue in the study. 
c) In cases where the subject is deemed ‘lost to follow up’, the investigator or 
designee must make every effort to regain contact with the subject (where 
possible, at least2telephone calls). The contact attempt should be 
documented in the subject’s record. 
d) Should the subject continue to be unreachable, only then will he/she be 
considered to have withdrawn from the study with a primary reason of “Lost 
to Follow-up”.
4.5. Subject Replacement
Subjects who withdraw from the study post-randomization will notbe replaced.
4.6. Subject and Study Completion
A completed subject is one who has completed all phases of the study.
The end of the study is defined as the date of the last subject’s last visit.
 
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5. PRODUCT INFORMATION
5.1. Study Product
The following study products will be supplied by the Clinical Supplies Department, 
GSKCH:
Test Product 1
Test Product 2 
Test Product 3 Test Product 4
Reference 
Product 1
Product Name 
Experimental 
Daily Defense 
Serum A
Experimental 
Daily Defense 
Serum C
Experimental 
Daily Defense 
Serum G
Experimental 
Daily Defense 
Serum N
Saline Solution 
Sodium 
Chloride
(NaCl
aq; 0.9%)
Product 
Formulation 
Code (MFC)
N/A
Site to supply
Dose
0.02ml/cm2
0.02ml/cm2
0.02ml/cm2
0.02ml/cm2
0.02ml/cm2
Route of 
Administration
Topical 
application via 
semi occlusive 
patch
Topical 
application via 
semi occlusive 
patch
Topical 
application via 
semi occlusive 
patch
Topical 
application via 
semi occlusive 
patch
Topical 
application via 
semi occlusive 
patch
5.2. Dose Schedule
Subjects will be exposed to a 24 ±2 hour dermal application of the four experimental 
daily defenseserumformulationsand negative control.Patches willbe applied by 
trained staff at the study site.
Subjects will be instructed to keep the patches dry and in place for 24± 2 hours. The 
subjects will be asked to return to the clinic where the patches will be removed and 
discarded. Upon removal of the patches, the subjects will be asked to wait in the 
clinic for assessments to be made15-30 minutes post patch removal. Subjects will 
then return to the clinic for two additional assessments at24 ± 2 and 48 ± 2 hours 
afterpatch removal.
The study products will be applied to discs (or cells) of the patch test adhesive tape. 
The number of cells available on the patch test tape is 6(but only 5 cells will be 
used).
 
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5.3.Overdose
An overdose is a deliberate or inadvertent administration of a product at a dose higher 
than specified in the protocol.
Overdose is not likely to occur in this study.  Limited quantities of the product will be 
supplied, and closely monitored by the site for each subject.
Overdose per se is not an AE.  However, any clinical sequelae of anoverdose should 
be reported as an AE (and serious adverse event (SAE), if appropriate).  For 
reporting, follow the AE and SAE reporting instructions.
5.4. Product Assignment
Each subject will have all 4 test products and the negative control applied to their 
backs(dorsum region). The location for each study product application for each 
subject will be assigned in accordance with the randomization schedule generated by 
the Biostatistics Department, GSKCH, prior to the start of the study, using validated 
internal software.
5.4.1 Randomization
A unique screening number will identify each subject screened for study 
participation.  Screening numbers will be assigned in ascending numerical order as 
each subject signs their consent form.  Subjects who meet all inclusion and exclusion 
criteria will be randomized according to the randomization schedule.  Randomization 
numbers will be assigned in ascending numerical order as each subject is determined 
to be fully eligible.The randomization number will be associated with the random 
location assignment of product to test site.
5.4.2 Blinding
The study statistician and other employees of the Sponsor who may influence study 
outcomes are blinded to the product allocation/test site location.Investigators 
dispensing the product will be aware of each product’s location and must not divulge 
information to the study staff or assessors. The assessorperforming the assessment of 
irritation will be blinded to the product allocation.
 
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5.4.3 Code Breaks
The blind must only be broken in an emergency where it is essential to know where 
eachproduct was applied on a subjectin order to give the appropriate medical care.  
Wherever possible the Investigator (or designee) must contact the Sponsor prior to 
breaking the blind.  The investigator must document the reason for breaking the code 
and sign and date the appropriate document.
The study blind must be returned toGSKCH at the end of the study.
5.5. Packaging and Labelling
The contents of the label will be in accordance with all applicable regulatory 
requirements and will be the responsibility of the Clinical Supplies Department, 
GSKCH.
The Experimental daily defenceserums (
) will be suppliedinpump packswitha study label 
affixedby the Sponsor.Each study label will contain, but not be limited to, protocol 
number, product codeletter and directions for storage.
The investigator or designee will supply the salinesolution (Reference Product 1) 
with a study label affixed. Each study label will contain the information according to 
the site specific internal 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. 
5.5.1. Accountability of Product
All products supplied are for use only in this clinical study and should notbe used for 
any other purpose.Products are only to be used and applied by the study site 
technician.
The investigator or designee will maintain a full record of study product 
accountability. A Product Dispensing Log must be kept current and will contain the 
following information:
The identification of the subject to whom the study product was dispensed.
 
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The inventory must be available for inspection by the study monitor during the study. 
At the end of the study, study product supplies will be verified by the monitor.  
Study product supplies should not be destroyed without prior written authorization by 
the Sponsor.When destruction of the study products takes place a dated certificate of, 
or receipt for destruction, will be provided to the Sponsor. 
5.5.2. Storageof Product
Study product supplies must be stored in compliance with the label requirements in a 
secure place with limited or controlled access.
6. STUDY ASSESSMENTS AND PROCEDURES
This section lists the procedures and parameters of each planned study 
assessment/Visit.  The exact timing of each assessment is listed in the Schedule of 
Events section.
Adherence to the study design requirements, including all assessments and 
procedures are essential and required for study conduct.
6.1. Visit 1 -Screening Visit
6.1.1 Telephone Screening
Prior to the screening visit, telephone screening of interested subjects maybe 
conducted using a telephone script. This will be conducted by the site recruitment 
staff or designee.  Subjects who successfully complete the telephone screening will be 
scheduled for the Screening Visit. At the Screening Visit, the following procedures 
will be completed:
6.1.2Informed Consent
The investigator, or designee, must obtain written (signed and dated by the subject) 
informed consent from each subject participating in this study after adequate 
explanation of the aims, methods, objectives, and potential hazards of the study.
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 writtenSIGNED AND DATEDconsent will 
be provided by the investigator or by GSKCH.  The investigator, or designee, should 
 
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sign and date the consent form to confirm that the consent process was completed 
correctlyafter the subject has signed.  The subjectwill be provided with a copy of 
their signed and dated consent form and any other written information which they are
be instructed to retain.
If, during a subject’s participation in the study, any new information becomes 
available that may affect the subject’s willingness to participate in the study, each 
ongoing subject should receive a copy of this new information and be re-consented 
into the study. Subjects should be provided with a copy of the signed and dated 
amended consent form. The date of consent will be recorded on the CRF.
After signing the Informed Consent Form (ICF), subjects will undergo all the 
screening assessments to confirm that they meet all the inclusion criteria and none of 
the exclusion criteria.If the subject is considered eligible by the Investigator (or 
designee) to participate they are considered enrolled in the study.
6.1.3Demographics
The following demographic parameters will be captured by the Investigator or 
designee and recorded on the CRF: Fitzpatrick skin type scale, year of birth, gender 
and race.
6.1.4Medical History and Concomitant Medication
Medical history will be assessed as related to the inclusion/exclusion criteria by the 
Investigator or medically qualified designee.  Details of any relevant medical or 
surgical history (within the last year), includingallergies or drug sensitivity, will be 
recorded on the CRF.  Any concomitant therapy taken in the 30 daysprior to the 
Screening Visit and throughout the study will also be recorded.
6.2 Visit 2 (Day 1), Visit 3 (Day 2) and Visit 4 (Day 3)
Visit 2 may be combined with Visit 1 (Screening) but should be no more than 7 days 
following Visit 1. 
At Visit 2 any concomitant therapy takenwill be reviewed, and continued eligibility 
will be checked before product application (and randomisation of product application 
ordering). This will be reviewed again before each subsequent visit.
 
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6.2.1Application of patches
Test productsand control (0.02ml/cm
2of each product) will be applied to a 1.2cm
2
paper disc (or cell) contained withinan adhesive patch (measuring 65cm
2). The 
number of cells available on the patch test tape is 6 (but only 5 cells will be used). 
The patch is then applied ontothe dorsum (scapula region) of each subjectfor a 
period of 24 ± 2hours, the sequence of the product application to the cells will be 
according tothe randomization schedule.
Patch assessments will be performed at Visit 3,4 and 5 per section 6.3.
6.3PatchAssessments 
Experienced trained assessor(s)will assess all patch sites for the duration of the study
according tothe scoring scale in Appendix 2. Where ever possible the same 
experienced trained assessor will perform all skinassessmentsfor a given subjectat 
each time point; 15-30minutes post patch removal(Visit 3, Day 2)in addition to24± 
2(Visit 4, Day 3)and 48± 2 hours(Visit 5, Day 4) post patch removal. Patch sites 
will be graded usinga magnifying glass with a fluorescent daylight lamp.The 
assessor will beblinded to the treatment allocation.
The results will be presented as individual responses to each test product at each 
assessment time point.
In any case of a positive reactionadermatologist will be available to perform 
secondary assessments and gradethe response with any further action as needed.This 
should occur the same day as the initial assessment performed by the trained assessor.
The intensity of any visual signs of irritation will be recorded by the trained 
examiner, according to the quantity and grade of the reactions (Appendix 2) 
according to the skin appearance (Scale 1) and other features indicative of irritation 
(Scale 2) observed.The trained examiner is responsible for grading the reactions, and 
the trained examiner’s opinion on the interpretation of the results is final.
Any observed response which can be denoted using the irritation criteria 
summarized in Appendix 2, will not be considered an adverse event. In addition
any tape-related irritation will also not be noted as an AE. Only in case of 
unusual reactions, these reactions and the consequences upon the evaluation of 
the respective test areas will be documented as AE’s.
 
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All responses will be reviewed in context of the grading scale in this protocol 
(Appendix 2).
6.4Visit 5 (Day 4) Study Conclusion
Final review of any concomitant therapy takenadverse events experienced since the 
last visitand continued eligibilitywill be performedbefore final patch assessment (48 
± 2 hours) as per Section 6.3.
Subjects will be evaluated to determine if they completed all study procedures or if 
they were discontinued from the study early.  If the subject discontinued at any point 
during the study, the primary reason for withdrawal should be recorded on the Study 
Conclusion page of the CRF by selecting one of the options below.
1.
Subject did not meet study criteria
2.
Adverse Event
3.
Lost toFollow Up
4.
Protocol Violation
5.
Withdrawal of Consent
6.
Other
7. SAFETY ASSESSMENTS
7.1. Definitions of an Adverse Event and Serious Adverse Event 
7.1.1. Adverse Events
The investigator or site staff will be responsible for detecting, documenting and
reporting events that meet the definition of an AE or SAE.
Adverse Event Definition:
An AE is any untoward medical occurrence in a patient or clinical investigation 
subject, temporally associated with the use of an investigational or washout product, 
whether or not considered related to the investigational or washout product.
NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of an investigational or washout product.
Events meeting AE definition include:
Any abnormal laboratory test results (if applicable) or other safety assessments, 
 
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including those that worsen from baseline, and felt to be clinically significant in the 
medical and scientific judgment of the investigator.
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.
New condition(s) detected or diagnosed after study product administration even 
though it may have been present prior to the start of the study.
Signs, symptoms, or the clinical sequelae of a suspected 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).
Events NOT meeting definition of an AE include:
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/ condition being studied or expected progression, signs, or 
symptoms of the disease/disorder being studied, unless more severe than expected for 
the subject’s condition.. 
Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is an AE.
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 which can be denoted using the irritation criteria 
summarized in Appendix 2, will not be considered an adverse event. In addition 
any tape-related irritation will also not be noted as an AE. Only in case of 
unusual reactions, these reactions and the consequences upon the evaluation of 
the respective test areas willbe documented as AE’s.
 
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7.1.2. Serious Adverse Events
Serious Adverse Event is defined as any untoward medical occurrence that, at 
any dose:
A. Results in death
B. Is life-threatening
NOTE: The term 
'life-threatening
' in the definition of 
'serious
' refers toan 
event in which the subject was at risk of death at the time of the event.  It does 
not refer to an event, which hypothetically might have caused death, if it were 
more severe.
C. Requires hospitalization or prolongation of existing hospitalization
NOTE: In general, hospitalization signifies that the subject has been detained 
(usually involving at least an overnight stay) at the hospital or emergency 
ward for observation and/or treatment that would not have been appropriate in 
the physician’s office or out-patient setting.  Complications that occur during 
hospitalization are AEs.  If a complication prolongs hospitalization or fulfills 
any other serious criteria, the event is serious.  When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered 
serious.
Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE.
D. Results in disability/incapacity
NOTE: The term disability means a substantial disruption of a person’s ability 
to conduct normal life functions.
This definition is not intended to include experiences of relatively minor 
medical significance such as uncomplicated headache, nausea, vomiting, 
diarrhea, influenza, and accidental trauma (e.g. sprained ankle) which may 
interfere or prevent everyday life functions but do not constitute a substantial 
disruption.
E. Is a congenital anomaly/birth defect
F. Other Situations
Medical or scientific judgment should be exercised in deciding whether 
reporting is appropriate in other situations, such as important medical events 
that may not be immediately life-threatening or result in death or 
hospitalization but may jeopardize the subject or may require medical or 
surgical intervention to prevent one of the other outcomes listed in the above 
definition. These should also be considered serious.
Examples of such events are invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization or development 
of drug dependency or drug abuse or reports of spontaneous abortion.
 
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7.2. RecordingAdverse Eventsand Serious Adverse Events
Recording of adverse events and serious adverse events:
The investigator or sitestaff will be responsible for detecting, documenting and 
reporting events that meet the definition of an AE or SAE. 
The investigator or site staff will then record all relevant information regarding an 
AE/SAE in the CRF.
There may be instances when copies of medical records for certain cases are 
requested by GSK.  In this instance, all subject identifiers, with the exception of the 
subject number, will be blinded on the copies of the medical records prior to 
submission to GSK.
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  In such cases, the diagnosis will be 
documented as the AE/SAE and not the individual signs/symptoms. Clinical AEs will 
be described by diagnosis and not by symptoms when possible (e.g., upper respiratory 
tract infection, seasonal allergy, etc. instead of runny nose).
AEs will be collected from the start of the product application anduntil 5days 
following last administration of the study product.
SAEs willbe collected over the same time period as stated above for AEs.  However, 
any SAEs assessed as relatedto study participation (e.g., investigational product, 
protocol mandated procedures, invasive tests, or change in existing therapy) or related 
to a GSK concomitant medication will be recorded from the time a subject consents 
to participate in the study up to and including any follow-up contact.  
Medical conditions reported prior to the time period for reporting AEs/SAEs should 
be recorded as part of the subject’s medical history.
7.3. Evaluating Adverse Eventsand Serious Adverse Events
Assessment of Intensity:
The investigator or designee will make an assessment of intensity for each AE and 
SAE reported during the study and will assign it to one of the following categories:
Mild:  An event that is easily tolerated by the subject, causing minimal discomfort 
 
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and not interfering with everyday activities.
Moderate:  An event that is sufficiently discomforting to interfere with normal 
everyday activities
Severe:  An event that prevents normal everyday activities. -AnAE that is 
assessed as severe will not be confused with an SAE. Severity is a category 
utilized for rating the intensity of an event; and both AEs and SAEs can be 
assessed as severe.
Note: An event is defined as ‘serious’ when it meets at least one of the pre-defined 
outcomes as described in the definition of an SAE.
Assessment of Causality:
The investigator is obligated to assess the relationship between study product and the 
occurrence of each AE/SAE.
A "reasonable possibility" is meant to convey that there are facts/evidence or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled 
out.
The investigator will use clinical judgment to determine the relationship.
Alternative causes, such as natural history of the underlying diseases, concomitant 
therapy, other risk factors, and the temporal relationship of the event to the study 
product will be considered and investigated.
The investigator will also consult the Investigator Brochure (IB) and/or Product 
Information, for marketed products, in the determination of his/her assessment.
For each AE/SAE the investigator must document in the medical notes (source 
document) or CRF that he/she has reviewed the AE/SAE and has provided an 
assessment of causality.
There may be situations when an SAE has occurred and the investigator has minimal 
information to include in the initial report to GSK.  However, it is very important 
that the investigator always make an assessment of causality for every event 
prior to the initial transmission of the SAE data to GSK.
The investigator may change his/her opinion of causality in light of follow-up 
 
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information, amending the SAE data collection tool accordingly.
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
7.4. Reporting Adverse Eventsand Serious Adverse Events
AE Reporting to GSKCH:
AEs will be recorded in the AE section of the CRF. 
Medical conditions recorded by the subject ona diary card or similar document that 
meet the definition of an AE must also be recorded in the AE section of the CRF, if 
not previously well-characterized by the investigator in the subject’s medical history. 
AEs elicited by the investigator in a standard manner at the study visits should also be 
recorded in the AE section of the CRF.  The investigator or designee must ask the 
subject the following question during each visit including any follow-up visits:  
“Have you felt unwell, experienced any symptomsor taken any medication (since 
your last visit) (today) (since your last dose) (since the last session)?”
The medically qualified investigator should review adverse events in a timely 
manner; this review should be documented in writing in the source document or in the 
CRF. 
After the study is completed at a given site, and the site has received their study data 
on Compact Discs (CDs), the electronic data collection tool will be removed from the 
internet to prevent the entry of new data or changes to existing data.
SAE Reporting to GSKCH:
A paper copy of the SAE form provided in the investigator study master file should 
be completed as fully as possible. 
It is essential to enter the following information: 
1. Protocol and subject identifiers
2. Subject’s demography
3. Description of events, with diagnosis if available
4. Investigator opinion of relationship to study product 
5. Criterion for seriousness.
The following are desirable and are of particular relevance for investigator and 
 
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GSKCH assessment of the SAE report:
1. Date of onset of AE 
2. Date AE stopped, if relevant
3. Study product start date
4. Study product end date if relevant
5. Action taken on study product
6. Outcome if known
The SAE form, completed as fully as possible, and SAE fax cover sheet must be 
faxed or e-mailed to the appropriate SAE Coordinatoras soon as possible, but not 
later than 24 hoursafter study site personnel learn of the event. The SAE 
Coordinatorshould be notified of the situation by telephone or email.
Brazil SAE Coordinator (Rafaela Ross):
Tel: 
E-mail:
Brazil backup contact (Ricardo Vila):
Tel: 
The SAE Coordinatorwill be responsible for forwarding the SAE form to the Case 
Management Group, Global Clinical Safety and Pharmacovigilance,the Medical 
Director responsible for the study and other GSKCH personnel as appropriate via 
email.
The initial report will be followed up with more information as relevant, or as 
requested by the GSKCH study manager.
7.5. Follow-up of Adverse Eventsand Serious Adverse Events
Follow-up of AEs and SAEs:
After the initial report, the investigator is required to proactively follow up with each 
subject and provide further information on the subject’s condition.
All AEs/SAEs will be followed until resolution, until the condition stabilizes, until 
the event is otherwise explained, or until the subject is lost to follow-up.  
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as may be indicated or as requested by GSK to 
elucidate as fully as possible the nature and/or causality of the AE or SAE.
Investigators are not obliged to actively seek AEs or SAEs in former subjects.  
 
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PPD
PPD
PPD

However, if the investigator learns of any SAE, including the death, at any time after 
a subject has been discharged from the study, and considers the event reasonably 
related to the investigational product or study participation, the investigator will 
promptly notify GSKCH.
The investigator will submit any updated AE or SAE data to GSK within the 
designated reporting time frames.
Regulatory and ethics reporting requirements for SAEs:
The investigator will promptly report all SAEs to GSKCH within the designated 
reporting timeframes (within 24 hours of learning of the event). GSKCH has a legal 
responsibility to notify, as appropriate, the local regulatory authority and other 
regulatory authorities about the safety of a product under clinical investigation.  
Prompt notification of SAEs by the investigator to GSKCH is essential so that legal 
obligations and ethical responsibilities towards the safety of subjects are met.
GSKCH will comply with country specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRB/IECand investigators.
Investigatorsafety reports are prepared according to GSKCH policy and are 
forwarded to investigators as necessary.  An investigator safety report is prepared for 
a SAE(s) that is both attributable to investigational product and unexpected.  The 
purpose of the report is to fulfill specific regulatory and GCP requirements, regarding 
the product under investigation.
An investigator who receives an investigator safety report describing a SAE(s) or 
other specific safety information (e.g., summary of listing of SAEs) from GSKCH 
will file it with the Investigator Brochure (or safety statement) and will notify the IRB 
or IEC,if appropriate according to local requirements.
7.6. Collection of Pregnancy Information
7.6.1. Time Period for Collectingof Pregnancy Information
Collection of Pregnancy Information:
Pregnancy information will be collected on all pregnancies reported following 
administration of any investigational product.
Information on pregnancy identified during the screening phase and prior to 
 
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investigational product administration does not need to be collected.
7.6.2. Action to be Taken ifPregnancy Occurs
Action to be Taken:
The investigator will collect pregnancy information on any subject who becomes 
pregnant while participating in the study after administration of the investigational 
product. The investigator will record pregnancy information on the appropriate form 
and submit it to GSKCH within 2 weeks of learning of the subject becoming 
pregnant. The subject will be followed to determine the outcome of thepregnancy. 
Information on the status of the mother and infant / neonate (including concomitant 
medications taken by the mother during the pregnancy) will be forwarded to GSKCH. 
Generally, follow-up will be no longer than 6 to 8 weeks following the estimated 
delivery date. Any termination of the pregnancy will be reported.
While pregnancy itself is not considered to be an AE, any pregnancy complication or 
elective termination for medical reasons will be recorded as an AE or SAE.
A spontaneous abortion is always considered to be an SAE and will be reported as 
such. An SAE occurring in association with a pregnancy, brought to the investigator’s 
attention after the subject completed the study and considered by the investigator as 
possibly related to the investigational product, must be promptly forwarded to GSK.
While the investigator is not obliged to actively seek this information in former study 
participants, he or she may learn of an SAE through spontaneous reporting.
If the subject becomes pregnant during the study they should be withdrawn from the 
study and this should be recorded in the appropriate section of the CRF
8. DATA MANAGEMENT
For this study subject data will be entered into an electronic case report form, using a 
GSKCH validated data system.
8.1. Source Documents/ Data
The source documents (e.g. hospital records, clinical and office charts, laboratory 
notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing 
records, recorded data from automated instruments, microfiches,photographic 
 
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negatives, microfilm or magnetic media, x-rays, subject files and records kept at the 
pharmacy, at the laboratory and at the medico-technical departments involved in the 
clinical study) which contain the source of data recorded in the CRF should be 
specified in the Source Document Designation Form.  In some cases the printed CRF 
can be used as a source document.
Each subject will be assigned and identified by a unique Screening Number. Any 
reference made to an individual subject within the study must be done using the 
unique Screening Number.
8.2. Electronic Case Report Form
A CRF is a printed, optical, or electronic document designed to record all of the 
protocol required information to be reported to thesponsor on each trial subject.
For each subject who has given informed consent/assent and has been screened, CRF 
must be completed and signed by the Principal Investigator (or authorized designee) 
to certify that the data are complete and correct.  
Management of clinical data will be performed in accordance with applicable 
GSKCH standards and data cleaning procedures to ensure the integrity of the data e.g. 
removing errors and inconsistencies in the data. 
In order to protect the privacy of subjects, no Personally Identifiable Information 
(PII) (including the subject
's name or initials or birth date(day and month)) is to be 
recorded in the CRF or as part of the query text.
Adverse events and concomitant medications terms (if applicable) will be coded by 
the sponsor using MedDRA and an internal validated medication dictionary, 
GSKDrug.  
Subject data will be entered into GSKCH defined CRFs and transmitted electronically 
to GSKCH in a validated (21 CFR Part 11 compliant) web-based electronic data 
capture system (InForm
TM).
All CRF pages should be completed during a subject assessment when the CRF has 
been designated as the source.  Data that is sourced elsewhere should be entered into 
the CRF in an agreed upon timeframe between the Investigator and Sponsor.  
The CRFs (including queries, query responses and audit trails) will be retained by 
GSKCH. Site data archived compact discs (CD(s)) prepared by a third party will be 
 
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sent to the investigator to maintain as the investigator copy following the 
decommissioning of the study.
8.3. Data Handling
Documentation of all data management activities should allow step-by-step 
retrospective assessment of data quality and study performance. Any changes or 
corrections to data will be performed in the Electronic Data Capture (EDC) System, 
and it will include rationale for changes. The EDC system has an audit trail, which 
will provide a complete record of the changes and corrections endorsed by the 
Investigator.
Protocol deviations are any changes or discrepancies from the protocol that have not 
been approved by IRB. Protocol procedures should be fully
 followed, taking 
appropriate action to prevent any deviations from protocol. However, in case of 
intercurrences, it is up to the Investigator to analyze the occurrence, as well as the 
measures that should be taken for the incident.
Any deviation from the plan of this protocol should be described and justified in the 
final report and submitted to the IRB
8.3.1. Data Queries
Programmed edit checks will be generated automatically, as the data is being entered 
into the system. Data Management will also run reports and listings on the CRF data, 
in addition to the queries already programmed and generated by the system, to raise 
manual queries as needed for site clarification or correction. The Clinical Dictionary 
Developmentand Management Group will raise queries as needed on safety data to 
code the terms (Adverse Events and Drugs) and reportappropriately. 
The study monitor at the study site will review the CRFs in accordance with the 
monitoring plan, and any queries will be generated in the EDC System to the 
Investigator or designee, enabling the errors to be addressed in parallel with Data 
Management review. Monitor can also run reports and listings on the CRFs, to raise 
manual queries as needed for site clarification or correction.
 
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9. STATISTICAL CONSIDERATIONS AND DATA 
ANALYSES
9.1.Sample Size Determination
The primary evaluation will be irritation scores after patch removal for each test
product at each assessment
No statistical analyses will be performed in this study. The number of subjects to be 
assessed (N=30completing the study) was based on clinical considerations.
9.2.General Considerations
9.2.1.Definition of Analysis Populations
The ‘Intent to treat’(ITT) population includes all subjects who are randomised into 
the study and have skin irritation scores from at least one of the test sites available.
Since this is a study to evaluate safety and tolerability, a separate Per Protocol (PP) 
analysis will not be performed.Protocol deviationswill however be listed for review.
The Safety population includes all subjects who received any of the test products. All 
safety analyses will be performed using the Safety population.
9.2.2.Exclusion of Data from Analysis
No data will be excluded from any analysis.
9.2.3.Criteria for Evaluation
The primary objective will be to assess the skin irritation potential of the test 
formulations, based on the irritancy score after patch removal.The study will be 
considered a success if no irritation is observed which is attributable to the test 
product at any time point.The study will be considered a success if no irritation is 
observedwhich is attributable to the test product at any time point, or if any 
observed irritation for the test product is not clinically differentiable from the 
saline solution
Safety and tolerability will be evaluatedby adverse events assessments.
 
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9.2.4.Handling of Dropouts and Missing Data
Missing data will not be replaced or imputed. Dropouts will be included in analyses 
up to the point of discontinuation.
9.3. Statistical Methods and Analytical Plan
Additional details of the proposed statistical analysis will be documented in the 
statistical analysis plan (SAP), which will be written following finalization of the 
protocol and prior to study unblinding / analysis (as appropriate).
9.3.1. Demographic and Baseline Characteristics
Age will be summarized descriptively using means, medians and standard deviations. 
Gender, race, and Fitzpatrick skin typewill be summarized using frequency counts 
and percentages.
9.3.2. Primary Analysis(es)
The primary analysis will be based on the irritation scores assessed using the dermal 
scale described in Scale1 of Appendix 2. No formal statistical inference will be 
performed. Summary statistics will be presented by productgroup for skin irritation 
scores at 15-30 mins, 24 and 48 hoursafter patch removal. Thiswill include mean 
irritation scores(if any subjects have reported/developedirritation)and the number 
and percentage of subjects recording each category of skinirritation scores.
9.3.3. Secondary Analysis(es)
Other skin effects, if manifest, will be assessed using the scale described in Scale2 of 
Appendix 2.These effects will be summarized descriptively as the number and
percent of subjects reporting each category of score. A combined dermal and other 
effects score will also be derived as the sum of these 2 scores. This combined score 
will also be summarized descriptively as the number andpercent of subjects 
reporting/developingeach category of score.
9.3.4. Safety Analysis(es)
Adverse Events (AE) will be tabulated according to the current version of the 
MedDRA. Frequencies and percentages will be presented overall, for each system 
organ class, and for each preferred term. Summaries of treatment-emergent AEs, 
treatment-related AEs, AEs leading to discontinuation, and serious AEs will be 
 
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completed. For treatment-related AEs, these will also be presented by product 
group/test site.
10. STUDY GOVERNANCE CONSIDERATIONS
10.1.Posting of Information on Publicly Available Clinical Trials 
Registers
Study information from this protocol will be posted on publicly available clinical trial 
registers before enrollment of subjects begins.
10.2.Regulatory and Ethical Considerations, Including the Informed 
Consent
The study will be conducted in accordance with all applicable regulatory 
requirements(Resolution nº 466 de 12 December 2012), and with GSK policy.
The study will also be conducted in accordance with ICH GCPand all applicable 
subject privacy requirements. This includes, but isnot limited to, the following:
1. Before initiating a trial, the investigator/institution should have written and 
dated approval/favorable opinion from the IRB/IECfor the trial protocol 
(including amendments), written informed consent form, consent form 
updates, subject recruitment procedures (e.g., advertisements), investigator 
brochure/ safety statement (including any updates) and any other written 
information to be provided to subjects. A letter or certificate of approval will 
be sent by the investigator to the sponsor prior to initiation of the study, and 
also when subsequent amendments to the protocol are made.
2. Signed informed consent  to be obtained for each subject before participation 
in the study (and for amendments as applicable)
3. Investigator reporting requirements (e.g. reporting of AEs/SAEs/protocol 
deviations to IRB/IEC)
4. GSK will provide full details of the above procedures, either verbally, in 
writing, or both.
The informed consent will also contain the following: As with any other product, this 
product may cause unexpected reactions, such as “redness”, “swelling”, “itching”, 
and “burning sensation” in the application site. However, all adverse reactions caused 
by the test product will be followed by a dermatologist until their resolution and 
appropriate medication will be provided if necessary. As A benefit for participating in 
 
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the study, subjects will be examined before the beginning of the study by an expert 
physician and, if any problem is identified in the relevant site, they will benotified 
and advised. Subjects may also learn about their correct skin tone/type (phototype) 
based on the procedures followed.
10.3.Quality Control (Study Monitoring)
In accordance with applicable regulations including GCP, and GSK procedures, GSK 
or designee (i.e. third party vendor) monitors will contact the site prior to the start of 
the study to review with the site staff the protocol, study requirements, and their 
responsibilities to satisfy regulatory, ethical, and GSK requirements.
When reviewing data collection procedures, the discussion will include identification, 
agreement and documentation of data items for which the CRF will serve as the 
source document.
GSK or designee will monitor the study and site activity to verify that the:
1. Data are authentic, accurate, and complete.
2. Safety and rights of subjects are being protected.
3. Study is conducted in accordance with the currently approved protocol and 
any other study agreements, GCP, and all applicable regulatory requirements.
The extent and nature of monitoring will be described in a written monitoring plan on 
file at GSKCH. The investigator (or designee) agrees to allow the monitor direct 
access to all relevant documents and agrees to co-operate with the monitor to ensure 
that any problems detected in the course of these monitoring visits are resolved.
10.4.Quality Assurance
To ensure compliance with GCP and all applicable regulatory requirements, GSK 
may conduct a quality assurance assessment and/or audit of the site records, and the 
regulatory agencies may conduct a regulatory inspection at any time during or after 
completion of the study. 
In the event of an assessment, audit or inspection, the investigator (and institution) 
must agree to grant the advisor(s), auditor(s) and inspector(s) direct access to all 
relevant documents and to allocate their time and the time of their staff to discuss the 
conduct of the study, any findings/relevant issues and to implement any corrective 
and/or preventative actions to address any findings/issues identified.
 
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The sponsor will be available to help investigators prepare for an inspection.
10.5.Conditions for Terminating the Study
Upon completion or premature discontinuation of the study, the GSKCH monitor will 
conduct site closure activities with the investigatoror site staff, as appropriate, in 
accordance with applicable regulations including GCP, and GSKCH Standard 
Operating Procedures.
Both GSKCH and the Investigator reserve the right to temporarily suspend or 
prematurely discontinue this study at any time forreasons including, but not limited 
to, safety or ethical issues or severe non-compliance. For multicenter studies (if 
applicable), this can occur atone or more or at all sites.  
If the trial is prematurely terminated or suspended for any reason, the investigator site 
should promptly inform the trial subjects and should assure appropriate therapy/ 
follow-up for the subjects. Where required by the applicable regulatory requirements, 
GSKCH should inform the regulatory authority (ies). 
In addition: 
1. If theinvestigator terminates or suspends a trial without prior agreement of 
GSKCH, the investigator site should promptly inform the sponsor and the 
IRB/IEC, and should provide the sponsor and the IRB/IECa detailed written 
explanation of the termination or suspension.
2. If the GSKCH terminates or suspends a trial, the investigator should promptly 
inform the IRB/IECand provide the IRB/IECa detailed written explanation of 
the termination or suspension. 
3. If the IRB/IECterminates or suspends its approval/favorableopinion of a trial, 
the investigator should promptly notify the GSKCH and provide GSKCH with 
a detailed written explanation of the termination or suspension.
10.6.Records Retention
Following closure of the study, the investigator must maintain all site study records 
(except for those required by local regulations to be maintained elsewhere), in a safe 
and secure location.  
The records (study/ site master file) must be maintained to allow easy and timely 
retrieval, when needed (e.g., for a GSK audit or regulatory inspection) and must be 
 
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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 actionis taken. 
The investigator must ensure that all reproductions are legible and are a true and 
accurate copy of the original and meet accessibility and retrieval standards, including 
re-generating a hard copy, if required.  Furthermore, the investigator must ensure 
there is an acceptable back-up of these reproductions and that an acceptable quality 
control process exists for making these reproductions.
The investigator must assure that the subject’s anonymity will be maintained.  On 
CRFs or other documents submitted to GSKCH, subjects should not be identified by 
their names or initials, but by an identification code. The investigator should keep a 
separate log of subjects’ codes, names and addresses.  Documents not for submission 
to GSKCH, e.g. subjects’ written consent forms, should be maintained by the 
investigator in strict confidence.
GSK will inform the investigator of the time period for retaining these records to 
comply with all applicable regulatory requirements (GSKCH recommends that 
documents be kept for 10 years). The investigator is also required to keep subject 
identification codes on file for at least 15 years after completion or discontinuation of 
the study. The minimum retention time will meet the strictest standard applicable to 
that site for the study, as dictated by any institutional requirements or local laws or 
regulations, GSK standards/procedures, and/or institutional requirements.  
No study document should be destroy
ed without a prior written agreement between 
GSKCH and the investigator. The investigator must notify GSK of any changes in the 
archival arrangements, including, but not limited to, archival at an off-site facility or 
transfer of ownership of the records in the event the investigator is no longer 
associated with the site.
10.7.Provision of Study Results to Investigators, posting of 
Information on Publicly Available Clinical Trials Registers and 
Publication
Where required by applicable regulatory requirements, an investigator signatory will 
be identified for the approval of the clinical study report.  The investigator will be 
 
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provided reasonable access to statistical tables, figures, and relevant reports and will 
have the opportunity to review the complete study results at a GSK site or other 
mutually-agreeable location.
GSK will also provide the investigator with the full summary of the study results.  
The investigator is encouraged to share the summary results with the study subjects, 
as appropriate.
The procedures and timing for public disclosure of the results summary and for 
development of a manuscript for publication will bein accordance with GSK Policy.
11. REFERENCES
ANVISA, Guideline for the Safety Evaluation of Cosmetics Products, 2012
Basketter, D. A., York, M., McFadden, J. P. and Robinson, M. K. (2004), 
Determination of skin irritation potential in the human 4-h patch test. Contact 
Dermatitis, 51:1–4
Birmingham, J. Clinical Aspects of Cutaneous Irritation and Sensitization, 
Toxicology and Applied Pharmacology 7:(54-59)
Bruze, M Recommendation of appropriate amounts of petrolatum preparation to be 
applied at patch testing* Contact Dermatitis 2007 0105-1873, 56(5):281
Dooms-Goossens, A, Corticosteroid contact allergy: an EECDRG Multicenter study
Contact Dermatitis, 1996, 0105-1873, 35(1):40
European Commission (EC) Regulation No 1223/2009of the European Parliament 
and of the Council of 30 November 2009on cosmetic products
Fitzpatrick, T.B., The validity and practicability of sun-reactive skin types I through 
VI.Arch. Dermatol.124, pp. 869-871, 1988
Guidance for Industry; Skin Irritation and Sensitization Testing of Generic 
Transdermal Drug Products, U.S. Department of Healthand Human Services
Food and Drug Administration Center for DrugEvaluation and Research (CDER) 
Federal Register. 1999;64(38):9516. 
ICH Topic 6 Guideline for Good Clinical PracticeCPMP/ICH/135/95 17thJuly 1996.
Isaksson, M., Gruvberger, B., Frick-Engfeldt, M. and Bruze, M. (2007), Which test 
chambers should be used for acetone, ethanol, and water solutions when patch 
testing? Contact Dermatitis, 57:134–136. doi:10.1111/j.1600-0536.2007.01094.x
LachapelleJ.-M., Maibach H. I, Patch Testing and Prick Testing, A practical Guide 
Official Publication of the ICDRG, 3rdEdition, 2012
Lee E, An S, Choi D, Moon S, Chang I. Comparison of objective and sensory skin 
irritations of several cosmetic preservatives. Contact Derm 2007; 56: 131-6.
World Medical Association Declaration of Helsinki, 59thGeneral Assembly, Seoul 
2008.
 
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12. APPENDICES
12.1. Appendix 1 -Abbreviations and Trademarks
Abbreviations
AE 
Adverse Event
ANVISA
Agência Nacional de Vigilância Sanitária
aq
Aqueous 
CD
Compact Disc
CRF
Case Report Form
EDC
Electronic Data Capture
FSFV
First Subject First Visit
GCP
Good Clinical Practice
GSK
GlaxoSmithKline
GSKCH
GlaxoSmithKline Consumer Healthcare
ICH
International Conference on Harmonization of Technical Requirements 
for Registration of Pharmaceuticals for Human Use
IEC
Independent Ethics Committee
ICF
Informed Consent Form
IRB
Institutional Review Board
ITT
Intention to Treat
LSLV
Last Subject Last Visit
MedDRA
Medical Dictionary for Regulatory Activities
PII
Personally Identifiable Information
PP
Per Protocol
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
 
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12.2. Appendix 2 –Skin Irritation Scoring System
Scale 1: Dermal Response
Score
Skin Appearance
0
No evidence of irritation
1 
Minimalerythema, barely perceptible
2 
Definiteerythema, readily visible; minimal edema or minimal 
papular response
3
Erythema and papules
4
Definite edema
5
Erythema, edema and papules
6
Vesicular eruption
7
Strong reaction spreading beyond test site
Effects on superficial layers of the skin should be recorded as follows:
Scale 2: Other Effects
Score (Numeric equivalent)
Observation
A (0)
Slight glazed appearance 
B (1)
Marked glazed appearance
C (2)
Glazing with peeling and cracking 
F(3)
Glazing with fissures 
G(3)
Film of dried serous exudate covering all or portion 
of the patch site 
H(3)
Small petechial erosions and/or scabs 
When an “Other Effects” score is observed, each score should be reported as a 
number and letter combination score and also as a numerical total (i.e. numerical 
“Dermal Response” score + numeric equivalent for the “Other Effects” lettered 
score).
A “Strong" reaction to the test patch isdefined as a ‘dermal response’score of 3-7 or any 
dermal scorecombined with ‘othereffects’ratingof 4.
 
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12.3. Appendix 3-Fitzpatrick Skin Type Grading
The Fitzpatrick 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). 
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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