A Clinical Study to Assess the Local Cutaneous and Ocular Tolerance of a Developmental Cosmetic Facial Serum Formulation in Healthy Females With Sensitive Skin
Phase: NA
Conditions: Skin Care
Sponsor: GlaxoSmithKline

Author(s) 
APPROVALS
Name
Reason for Approval
Approval Date CET*(MM/DD/YYYY)
6/7/2018 11:16:42 AM
6/8/2018 7:08:08 AM
6/13/2018 6:11:37 AM
Document Name 
Scope 
Document Type 
Document Subtype 
Document ID 
Version 
Approved Date in CET* 
Pages 
*CET: Central European Time
1.0
52
Clinical Protocol
0900c35380e23408
Jun 13,2018  6:11:00 AM
209442-Clinical Protocol-Clinical Protocol
Clinical Protocol
Studies
003 Study protocol and Amendment
PPD
PPD
PPD
PPD

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May not be used, divulged, published or otherwise disclosed without the consent of GSK CH
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CLINICAL PROTOCOL
A Clinical Study to Assess the Local Cutaneous and Ocular
Tolerance of a Developmental Cosmetic Facial Serum 
Formulation in Healthy Females with Sensitive Skin
Protocol Number:
209442
Compound/Product Name:
Developmental Cosmetic Facial Serum
United States (US) Investigational 
New Drug (IND) Number:
Not Applicable
European Clinical Trials Database 
(EudraCT) Number:
Not Applicable
Other Regulatory Agency Identified 
Number:
Not Applicable
Phase:
Not Applicable
 
 
 
 
 
 

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Sponsor Information
Sponsor Name & Legal 
Registered Address
GlaxoSmithKline Research & Development 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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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 (IRBs/ECs), etc.  
 
 
 
 
 
 

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Principal Investigator Protocol Agreement Page

I confirm agreement to conduct the study in compliance with the protocol and any 
amendments according to the current International Conference on Harmonisation Good 
Clinical Practice (ICH GCP) guidelines.

I acknowledge that I am responsible for overall study conduct. I agree to personally 
conduct or supervise the described study.

I agree to ensure that all associates, colleagues and employees assisting in the conduct of 
the study are informed about their obligations. Mechanisms are in place to ensure site staff 
receives all appropriate information throughout the study.

I agree to conduct this study in full conformance with the laws and regulations of the 
country in which the research is conducted and the Declaration of Helsinki.
Investigator Name:
Investigator Qualifications:
Investigator Signature:
Date of Signature/Agreement:
DD-Mmm-YYYY
 
 
 
 
 
 
PPD
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Table of Contents
Document History................................................................................................................3
Principal Investigator Protocol Agreement Page.................................................................4
Table of Contents.................................................................................................................5
1
PROTOCOL SUMMARY.................................................................................................10
Schedule of Activities........................................................................................................13
2
INTRODUCTION .............................................................................................................14
2.1
Study Rationale......................................................................................................14
2.2
Background............................................................................................................15
2.3
Mechanism of Action/Indication ...........................................................................15
3
STUDY OBJECTIVES AND ENDPOINTS.....................................................................15
4
STUDY DESIGN ..............................................................................................................16
4.1
Overall Design .......................................................................................................16
4.2
Rationale for Study Design....................................................................................17
4.3
Justification for Dose .............................................................................................17
4.4
End of Study Definition.........................................................................................18
5
STUDY POPULATION....................................................................................................18
5.1
Type and Planned Number of Subjects..................................................................18
5.2
Inclusion Criteria....................................................................................................18
5.3
Exclusion Criteria ..................................................................................................19
5.4
Randomization Criteria..........................................................................................20
5.5
Lifestyle Considerations ........................................................................................20
5.6
Screen Failures.......................................................................................................21
5.7
Sponsor’s Qualified Medical Personnel.................................................................21
5.8
Clinical Assessor Qualifications............................................................................21
6
INVESTIGATIONAL/STUDY PRODUCTS...................................................................22
6.1
Investigational/Study Product Supplies .................................................................22
6.1.1
Dosage Form and Packaging.................................................................23
6.1.2
Preparation and Dispensing...................................................................23
6.2
Administration .......................................................................................................23
6.2.1
Dosing Errors.........................................................................................23
6.3
Investigational/Study Product Storage...................................................................24
6.4
Investigational/Study Product Accountability .......................................................24
6.4.1
Destruction of Investigational/Study Product Supplies.........................25
6.5
Blinding and Allocation/Randomization ...............................................................25
6.6
Breaking the Blind .................................................................................................25
6.7
Subject Compliance ...............................................................................................26
6.8
Concomitant Medication/Treatment(s)..................................................................26
7
DISCONTINUATION OF STUDY INTERVENTION AND SUBJECT 
DISCONTINUATION/WITHDRAWAL .........................................................................26
 
 
 
 
 
 

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7.1
Subject Discontinuation/Withdrawal.....................................................................26
7.2
Lost to Follow up...................................................................................................27
8
STUDY PROCEDURES...................................................................................................27
8.1
Visit 1 (Day 1) Screening/Baseline........................................................................27
8.1.1
Informed Consent..................................................................................27
8.1.2
Demographics........................................................................................28
8.1.3
Medical History and Prior Medication/Treatment ................................28
8.1.4
Inclusion/Exclusion Criteria..................................................................29
8.1.5
Subject self-assessment .........................................................................29
8.1.6
Dermatologist Assessment ....................................................................29
8.1.7
Ophthalmologist Assessment ................................................................29
8.1.8
Lactic Acid Stinging Test (LAST) ........................................................30
8.1.9
Subject Eligibility..................................................................................31
8.1.10
Randomization.......................................................................................31
8.1.11
Supervised Product Application............................................................31
8.2
Visit 2/Day 21 (Final Visit) ...................................................................................31
8.2.1
Dermatologist Assessment ....................................................................31
8.2.2
Ophthalmologist Assessment ................................................................32
8.2.3
Subject self-assessment .........................................................................32
8.3
Diary Review .........................................................................................................32
8.4
Study Conclusion...................................................................................................32
8.5
Follow-up Visit ......................................................................................................32
9
STUDY ASSESSMENTS .................................................................................................33
9.1
Screening Assessments ..........................................................................................33
9.2
Safety and Other Assessments...............................................................................33
9.2.1
Dermatologist Assessment of Signs and Symptoms of Cutaneous 
Irritation.................................................................................................33
9.2.2
Ophthalmologist Assessment of Signs and Symptoms of Ocular 
Irritation.................................................................................................33
9.2.3
Subject Self-Assessment of Signs and Symptoms of Cutaneous and 
Ocular Irritation.....................................................................................34
10 ADVERSE EVENT AND SERIOUS ADVERSE EVENTS............................................34
10.1
Definition of an Adverse Event (AE) ....................................................................34
10.2
Definition of a Serious Adverse Event (SAE) .......................................................35
10.3
Reporting of Adverse Events.................................................................................36
10.3.1
Reporting Period....................................................................................36
10.4
Reporting Procedures.............................................................................................37
10.4.1
Reporting of an Adverse Event .............................................................37
10.4.2
Reporting of a Serious Adverse Event ..................................................37
10.5
Evaluating Adverse Events....................................................................................38
 
 
 
 
 
 

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10.5.1
Assessment of Intensity.........................................................................38
10.5.2
Assessment of Causality........................................................................39
10.6
Follow-up of Adverse Events ................................................................................39
10.7
Withdrawal Due to an Adverse Event....................................................................40
10.7.1
Sponsor’s Reporting Requirements to Regulatory Authorities and 
Ethics Committees.................................................................................40
10.8
Pregnancy...............................................................................................................40
10.8.1
Time Period for Collecting Pregnancy Information..............................40
10.8.2
Action to be Taken if Pregnancy Occurs...............................................41
11 DATA MANAGEMENT ..................................................................................................41
11.1
Case Report Form ..................................................................................................41
11.2
Data Handling ........................................................................................................42
11.2.1
Data Queries..........................................................................................42
11.3
Processing Patient Reported Outcomes .................................................................42
12 STATISTICAL CONSIDERATIONS AND DATA ANALYSES...................................43
12.1
Sample Size Determination....................................................................................43
12.2
Statistical Methods and Analytical Plan ................................................................43
12.2.1
Definition of Analysis Populations .......................................................43
12.2.2
Exclusion of Data from Analysis ..........................................................43
12.2.3
Demographic and Baseline Characteristics...........................................43
12.2.4
Study Drug/Product Compliance...........................................................43
12.2.5
Prior and Concomitant Medications......................................................44
12.2.6
Primary Analysis(es) .............................................................................44
12.2.7
Secondary Analysis(es) .........................................................................44
12.2.8
Safety Analysis(es)................................................................................44
12.2.9
Other Analysis(es).................................................................................44
12.2.10
Handling of Dropouts and Missing Data...............................................44
12.2.11
Interim Analysis ....................................................................................45
13 STUDY GOVERNANCE CONSIDERATIONS..............................................................45
13.1
Quality Control ......................................................................................................45
13.2
Quality Assurance..................................................................................................45
13.3
Regulatory and Ethical Considerations..................................................................46
13.3.1
Institutional Review Board/ Ethics Committee.....................................46
13.3.2
Ethical Conduct of the Study.................................................................46
13.3.3
Subject Information and Consent..........................................................46
13.3.4
Subject Recruitment ..............................................................................46
13.3.5
Reporting of Safety Issues and Serious Breaches of the Protocol or 
ICH GCP ...............................................................................................47
13.4
Posting of Information on Publicly Available Clinical Trial Registers.................47
13.5
Provision of Study Results to Investigators...........................................................47
 
 
 
 
 
 

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13.6
Records Retention..................................................................................................47
13.7
Conditions for Terminating the Study ...................................................................48
14 REFERENCES ..................................................................................................................48
15 APPENDICES ...................................................................................................................49
15.1
APPENDIX 1 - ABBREVIATIONS .....................................................................49
15.2
APPENDIX 2 – FITZPATRICK SKIN TYPE GRADING...................................50
 
 
 
 
 
 

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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.................................................22
Table 8-1
Lactic Acid Sting Test Score.................................................................30
Table 9-1
Dermatological Evaluation....................................................................33
Table 9-2
Ophthalmological Evaluation................................................................34
Table 9-3
Subject Self-Assessment Scale for Signs and Symptoms of 
Cutaneous Irritation...............................................................................34
Table 9-4
Subject Self-Assessment Scale for Signs and Symptoms of Ocular 
Irritation.................................................................................................34
Table 15-1
Abbreviations ........................................................................................50
Table 15-2
FITZPATRICK SKIN TYPE GRADING.............................................50
 
 
 
 
 
 

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1
PROTOCOL SUMMARY 
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 with which to determine the irritation 
potential (local tolerance) of a cosmetic formulation to provide confidence the finished product 
is suitable for general sale.
The objective of this clinical study is to determine the local cutaneous and ocular tolerance of 
a developmental cosmetic facial serum in healthy females with sensitive facial skin under 
normal conditions of use. 
Objectives and Endpoints
Objective(s)
Endpoint(s)
Primary
To determine the local cutaneous tolerance
profile of the investigational product in 
healthy females with sensitive facial skin 
under normal conditions of use.
Change from baseline (prior to any product 
application) in dermatologist visual 
assessment scores of signs and symptoms 
of cutaneous irritation to 21 (+2) days of 
product use.
Secondary
To determine the local ocular tolerance 
profile of the investigational product in 
healthy females with sensitive facial skin 
under normal conditions of use.
Change from baseline (prior to any product 
application) in ophthalmologist visual 
assessment scores of signs and symptoms 
of ocular irritation to 21 (+2) days of product 
use.
To determine the local cutaneous and 
ocular tolerance of the investigational 
product from the perspective of the subject 
in healthy females with sensitive facial skin 
under normal conditions of use.
Change from baseline in subject self-
assessment scores of signs and symptoms 
of cutaneous and ocular irritation to 1-2 
hours after first product application and 
following 21 (+2) days of use.
Safety
To evaluate the general safety of two 
cosmetic facial serums.
Frequency and severity of Adverse Events.
Study Design
This is a randomized, evaluator-blind (dermatologist and ophthalmologist), 2-arm, parallel-
group, single-center, non-comparative clinical ‘in-use’ study to determine the local cutaneous 
and ocular tolerance of a developmental cosmetic facial serum formulation in healthy female 
subjects aged 18 to 65 years (inclusive) with clinically evaluated sensitive skin, as determined 
by a positive response to a Lactic Acid Sting Test (LAST), with minimal signs or symptoms of 
cutaneous irritation and no signs or symptoms of ocular irritation. A reference product, proven 
to be suitable for use in a sensitive skin population, is included to enable the study to be 
conducted in a randomized and blinded manner, rather than as a single-arm or open-label study, 
to minimize bias and ensure a robust outcome. 
 
 
 
 
 
 

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A sufficient number of subjects will be screened (approximately 180) to randomize 90 subjects 
to ensure that at least 60 subjects (30 per arm) complete the study. 
At Visit 1 (screening), subjects who agree to participate in the study by signing the informed 
consent will be assessed by a qualified dermatologist for baseline clinical assessments of the 
signs and symptoms of cutaneous irritation and by a qualified ophthalmologist for baseline 
clinical assessments of the signs and symptoms of ocular irritation. Following these 
assessments, a LAST will be conducted in the nasolabial region to confirm whether the subject 
has sensitive skin. Subjects will only be considered eligible to continue in the study if they 
present a positive response to the LAST. Medical history, Fitzpatrick skin type, prior, current 
and concomitant medication will also be recorded at this visit. Subjects will be asked to self-
assess baseline signs and symptoms of cutaneous and ocular irritation prior to the LAST and 
any product application.
Subjects will only be considered eligible to continue in the study if they have a dermatologist 
signs and symptoms cutaneous irritation score of greater than or equal to 0.5 (very slight) for 
erythema and a score of greater than or equal to 0.5 (very slight) for dryness, a score of 0 (none) 
or 0.5 (very slight) for scaling and 0 (none) or 0.5 (very slight) for edema. Any subject with a 
score of 3 (severe) in any cutaneous irritation attribute will exclude the subject from the study, 
as this does not reflect the target population for the product. Any ophthalmologist signs and 
symptoms attribute score of greater than 0 (none) will exclude the subject from the study. 
For subjects who continue to be eligible to participate in the study, 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 complete further self-assessment questions of the signs and symptoms 
of cutaneous and ocular irritation they are experiencing, 1-2 hours after first application. 
Subjects will then be instructed to apply their assigned product at home again the same evening 
and twice-daily for 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. The final application of product will be at home 
on the morning of the final visit (Visit 2).
At Visit 2 (final visit), 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 a final self-assessment of the signs and symptoms of cutaneous 
and ocular irritation. Subjects will return their completed diary and supplied product and will 
subsequently be discharged from the study.
Study Products
Subjects will be assigned to 1 of the 2 study products in accordance with the randomization 
schedule.
The investigational product is a developmental formulation intended to be used as a cosmetic 
facial serum by adult consumers with sensitive facial skin. The comparator product is a 
commercially marketed facial serum, also intended to be used 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.
 
 
 
 
 
 

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Type and Planned Number of Subjects
Healthy female subjects, aged 18 to 65 years with clinically assessed sensitive skin, and no 
ophthalmological conditions will be enrolled into this study. Female subjects with sensitive skin 
have been selected as they are the target consumers for the finished product with greater 
familiarization and habitual use of facial products.
A sufficient number of subjects will be screened (approximately 180) to randomize 90 subjects 
to ensure that at least 60 subjects (30 per arm) complete the study. It is deemed that 30 subjects 
per arm are considered sufficient to assess the primary endpoint: dermatologist assessment of 
signs and symptoms of cutaneous irritation total score. 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.
 
 
 
 
 
 

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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, in order to conduct evaluations or assessments required to protect the 
well-being of the subject.
Table 1-1
Schedule of Activities
Screening/Baseline
Final Visit
Procedure/Assessment
Visit 1
Day 1
Visit 2
Day 21 (+ 2)
Informed Consent 
(date and time captured)
X
Demographics
X
Medical History
X
Medications Review
X
X
Inclusion/Exclusion Criteria
X
Fitzpatrick Skin Type Assessment
X
Subject Self-Assessment
X a
X
Clinical Assessment by Dermatologist
X
X
Clinical Assessment by Ophthalmologist
X
X
Lactic Acid Sting Test (LAST)
X
Subject Eligibility for Enrollment
X
Randomization
X
Product and Diary Dispensing
X
Supervised Product Application b
X
Adverse Events (AEs) Review c
X
X
Product and Diary Return
X
X
Study Conclusion/Subject Exit from 
Study
X
a. Subject self-assessment on Visit 1 will occur twice; once prior to the LAST and product application 
and once 1-2 hours after first supervised product application.
b. Supervised product application should not occur until at least 30 minutes following the LAST.
c. 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).
Footnotes:
The diary will be used to maintain and record compliance and to capture subject comments.
The diary will be reviewed by the Investigator or their designee at final visit.
First product application will be conducted at the site under the supervision of the investigator or their 
designee.
 
 
 
 
 
 

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2
INTRODUCTION
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 on the market must not cause damage to human health when applied under 
normal or reasonably foreseeable conditions of use, taking into account, in particular, the 
product's presentation, its labelling, and any instructions. (Cosmetics Europe, 2004)
Skin contact with topical products such as cosmetics may trigger different types of reactions 
including eczema, contact dermatitis, urticaria, acne and spots.  Contact dermatitis can arise 
from two mechanisms: primary irritation, through the action of irritant substances; or 
sensitization, in the presence of an allergenic ingredient (Birmingham, 1965).
Clinical studies to evaluate the irritation and sensitization potential of a product must consider 
a number of variables including the components used in the formulation, ingredient 
concentration, absorption, amount applied, skin condition, application directions and frequency, 
as well as the cumulative effect (Dooms-Goossens, 1993). The most common form of 
intolerance to cosmetics is characterized by irritation, burning sensation, redness, pruritus and 
erythema at the application site (Lumelsky et al., 2001). 
Skin is characterized as ‘sensitive’ if it commonly presents a non-inflammatory response to 
application of topical products, as realized through subjective sensations such as 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 objective 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 clinically diagnose sensitive skin is a lactic acid sting test (LAST), 
whereby an aqueous solution of lactic acid is applied to the nasolabial fold to attempt to trigger 
a sensorial response, often alongside a placebo such as saline. The stinging sensation 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 clinical diagnosis and enrollment of 
subjects with sensitive skin into clinical trials to enable the local tolerance of an investigational 
product to be evaluate in this population. 
2.1
Study Rationale
GSK CH has developed a new cosmetic facial serum intended to be suitable for use by adult 
consumers with sensitive facial skin. Clinical data are required to demonstrate that the 
developmental formulation has a favorable local tolerance profile in the target population under 
normal conditions of use, prior to commercialization. 
Complete information for the developmental cosmetic facial serum and the comparator 
cosmetic facial serum may be found in the single reference safety document (SRSD), which for 
this study is the Safety Statement.
 
 
 
 
 
 

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2.2
Background
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 with which 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.
The investigational product is a developmental formulation intended to be used as a cosmetic 
serum by healthy adult consumers with sensitive facial skin. The formulation has been designed 
to provide topical moisturization while minimizing the quantity of known irritants and allergens. 
The objective of this clinical study is to determine the local cutaneous and ocular tolerance of 
a developmental facial serum product in healthy females with clinically confirmed sensitive 
facial skin under normal conditions of use.
2.3
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 product is a cosmetic facial 
serum that is intended to be applied topically by healthy female subjects with sensitive skin, 
immediately after cleansing.
Serum is a skincare product applied directly to the skin after cleansing but before moisturizing 
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 
odors and/or protecting or keeping in good condition (European Commission (EC), 2009). 
3
STUDY OBJECTIVES AND ENDPOINTS
Table 3-1
Study Objectives and Endpoints
Objective(s)
Endpoint(s)
Primary
To determine the local cutaneous tolerance
profile of the investigational product in 
healthy females with sensitive facial skin 
under normal conditions of use.
Change from baseline (prior to any product 
application) in dermatologist visual 
assessment scores of signs and symptoms 
of cutaneous irritation to 21 (+2) days of 
product use.
Secondary
To determine the local ocular tolerance 
profile of the investigational product in 
healthy females with sensitive facial skin 
under normal conditions of use.
Change from baseline (prior to any product 
application) in ophthalmologist visual 
assessment scores of signs and symptoms 
of ocular irritation to 21 (+2) days of product 
use.
To determine the local cutaneous and 
ocular tolerance of the investigational 
Change from baseline in subject self-
assessment scores of signs and symptoms 
 
 
 
 
 
 

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product from the perspective of the subject 
in healthy females with sensitive facial skin 
under normal conditions of use.
of cutaneous and ocular irritation to 1-2 
hours after first product application and 
following 21 (+2) days of use.
Safety
To evaluate the general safety of two 
cosmetic facial serums.
Frequency and severity of Adverse Events.
The objective of this clinical study is to determine the local tolerance profile of a developmental 
facial serum product in healthy females with sensitive facial skin under normal conditions of 
use, following 21 (+2) days twice daily application.
This study will be considered a success if at least 90% of completed subjects do not have a 
significant increase (i.e. a unit increase score of 1 in the total score) from baseline in 
dermatologist assessed signs and symptoms of cutaneous irritation following 21 (+2) days of 
investigational product use.
4
STUDY DESIGN 
4.1
Overall Design
This is a randomized, evaluator-blind (dermatologist and ophthalmologist), 2-arm, parallel-
group, single-center, non-comparative clinical ‘in-use’ study to determine the local cutaneous 
and ocular tolerance of a developmental cosmetic facial serum formulation in healthy female 
subjects aged 18 to 65 years (inclusive) with clinically evaluated sensitive skin, as determined 
by a positive response to a LAST, with minimal signs or symptoms of cutaneous irritation and 
no signs or symptoms of ocular irritation. A reference product, proven to be suitable for use in 
a sensitive skin population is included to enable the study to be conducted in a randomized and 
blinded manner, rather than as a single-arm or open-label study, to minimize bias and ensure a 
robust outcome. 
A sufficient number of subjects will be screened (approximately 180) to randomize 90 subjects 
to ensure that at least 60 subjects (30 per arm) complete the study. 
At Visit 1 (screening), subjects who agree to participate in the study by signing the informed 
consent will be assessed by a qualified dermatologist for baseline clinical assessments of the 
signs and symptoms of cutaneous irritation and by a qualified ophthalmologist for baseline 
clinical assessments of the signs and symptoms of ocular irritation. Following these 
assessments, a LAST will be conducted in the nasolabial region to confirm whether the subject 
has sensitive skin. Subjects will only be considered eligible to continue in the study if they 
present a positive response to the LAST. Medical history, Fitzpatrick skin type assessment, 
prior, current and concomitant medication will also be recorded at this visit. Subjects will be 
asked to self-assess baseline signs and symptoms of cutaneous and ocular irritation prior to the 
LAST and any product application.
Subjects will only be considered eligible to continue in the study if they have a dermatologist 
signs and symptoms cutaneous irritation score of greater than or equal to 0.5 (very slight) for 
erythema and a score of greater than or equal to 0.5 (very slight) for dryness, a score of 0 (none) 
or 0.5 (very slight) for scaling and 0 (none) or 0.5 (very slight) for edema. Any subject with a 
score of 3 (severe) in any cutaneous irritation attribute will exclude the subject from the study, 
as this does not reflect the target population for the product. Any ophthalmologist signs and 
symptoms attribute score of greater than 0 (none) will exclude the subject from the study. 
For subjects who continue to be eligible to participate in the study, the first application of their 
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Subjects will be asked to answer further self-assessment questions of the signs and symptoms 
of cutaneous and ocular irritation they are experiencing, 1-2 hours after first application. 
Subjects will then be instructed to apply their assigned product at home again the same evening 
and twice-daily for 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. The final application of product will be at home 
on the morning of the final visit (Visit 2).
At Visit 2 (final visit), 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 a final self-assessment of the signs and symptoms of cutaneous 
and ocular irritation. Subjects will return their completed diary and supplied product and will 
subsequently be discharged from the study.
4.2
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. 
The investigational product being evaluated is a developmental formulation intended to be used 
as a cosmetic facial serum by adult consumers with sensitive facial skin. The formulation has 
been designed to provide topical moisturization while minimizing the quantity of known 
irritants and allergens. A reference product, proven to be suitable for use in a sensitive skin 
population is included to enable the study to be conducted in a randomized and blinded manner, 
rather than as a single-arm or open-label study, to minimize bias and ensure a robust outcome. 
Subjects will only be considered eligible to continue in the study if they have a dermatologist 
signs and symptoms cutaneous irritation score of greater than or to equal 0.5 (very slight) for 
erythema and a score of greater than or equal to 0.5 (very slight) for dryness, as this is 
representative of the target consumer for the finished product. Subjects presenting a score 
greater than 0.5 (very mild) for edema and scaling are excluded from the study as they do not 
represent the target population for the product.
Any subject with a score of 3 (severe) in any cutaneous irritation attribute will exclude the 
subject from the study, as this does not reflect the target population for the product. 
Per ANVISA guidelines, acceptability studies are indicated to be conducted for a 3-week period 
of use, taking into account the normal conditions of use.
No formal statistical comparison between the reference product and investigational product is 
required in order to evaluate the local tolerance of the investigational product. 
4.3
Justification for Dose
The first administration will be supervised by a trained technician when the subjects are at the 
site at for Screening/Visit 1.
Subjects will be instructed to use the product twice-daily (morning and evening) as part of their 
normal facial care regimen, post cleansing and prior to moisturization (if appropriate), 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: “Apply twice daily to freshly cleansed skin in place of your current serum and before 
your moisturizer”.
Subjects who already use a facial serum will be instructed to replace their current serum with 
the product they have been assigned to use for the duration of the study. 
 
 
 
 
 
 

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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. 
5
STUDY POPULATION
5.1
Type and Planned Number of Subjects
Healthy female subjects, aged 18 to 65 years with clinically assessed sensitive skin and no 
ophthalmological conditions will be enrolled into this study. Female subjects with sensitive skin 
have been selected as they are the target consumers for the finished product with greater 
familiarization and habitual use of facial products.
A sufficient number of subjects will be screened (approximately 180) to randomize 90 subjects 
to ensure that at least 60 subjects (30 per arm) complete the study. It is deemed that 30 subjects 
per arm are considered sufficient to assess the primary endpoint: dermatologist assessment of 
signs and symptoms of cutaneous irritation total score. 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
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 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 of 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 
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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. A subject with sensitive facial skin, defined as a positive response to a lactic acid sting test 
in the nasolabial area.
6. A subject with a dermatologist signs and symptoms of cutaneous irritation score of greater 
than or equal to 0.5 (very slight) for erythema.
7. A subject with a dermatologist signs and symptoms of cutaneous irritation score of greater 
than or equal to 0.5 (very slight) for dryness.
8. A subject with a dermatologist signs and symptoms of cutaneous irritation score of 0 (none) 
or 0.5 (very sight) for scaling.
9. A subject with a dermatologist signs and symptoms of cutaneous irritation score of 0 (none) 
or 0.5 (very sight) for edema.
10. A subject with an ophthalmologist total signs and symptoms of ocular irritation score of 0 
(none).
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 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.
4. A subject who is pregnant (self-reported).
5. A subject who is breastfeeding.
6. A subject with known or suspected intolerance or hypersensitivity to the study materials (or 
closely related compounds) or any of their stated ingredients. 
7. A subject who, in the opinion of the investigator or medically qualified designee, should 
not participate in the study.
8. A subject unwilling or unable to comply with the Lifestyle Considerations required by this 
study, as described in this protocol. 
9. A subject with current or recent (within last 6 months before the start of the study) history 
of atopic lesions and/or eczema
10. A subject with a history of allergic reactions to topical-use products, cosmetics or 
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11. 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.
12. A subject presenting open sores, pimples, or cysts at the application site (face). 
13. A subject with an active dermatosis (local or disseminated) that might interfere with the 
results of the study.
14. A subject with a dermatologist signs and symptoms of cutaneous irritation score of 3 (severe) 
for erythema, edema, scaling or dryness.
15. A subject considered immune-compromised. 
16. A subject currently using any medication which in the opinion of the investigator, may 
affect the evaluation of the investigational product, or place the subject at undue risk
17. 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.
18. 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.
19. A subject who has been vaccinated up to 1 month before the screening visit or who are 
intending to receive a vaccination during their participation in the study.
20. A subject with a recent history (within the last 5 years) of alcohol or other substance abuse.
21. 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).
22. Subjects with corneal ulcers, keratoconus, blepharitis, meibomitis, pterygium, chemosis, 
moderately or severe hyperemia or other active ocular diseases.
23. A subject who has previously been enrolled in this study. 
5.4
Randomization Criteria
Subjects will be randomized into the study provided they have satisfied all subject selection 
criteria. 
5.5
Lifestyle Considerations
Following consent to participate in the study by completing the ICF, subjects may be asked to 
remove any leave on cosmetics (including make-up) prior to the visit assessments.
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, other than as defined in this protocol.

Introduction of new home care products which may come into contact with the skin, 
including laundry detergent, shower gel, shampoo, bath soap.

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
Undergoing any non-invasive, minimally-invasive or invasive cosmetic or surgical 
procedures on the face, e.g. waxing, bleaching etc. 
Visit 2:

Prior to the final visit (Visit 2), subjects must not apply any topical products (including 
leave-on 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 visit.

Subjects must refrain from drinking caffeinated drinks (e.g. coffee, tea, cola etc.) prior to 
Visit 2.
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 or incidents 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.  
5.8
Clinical Assessor Qualifications 
All clinical assessments will be made by a single qualified dermatologist and a single qualified 
ophthalmologist for all subjects throughout the study. Each assessor will visually assess subjects 
for eligibility to continue in the trial and at the end of the 21 (+2) day product use period.
The intensity of any visual signs of dermal irritation will be recorded according to the grade of 
the reactions in 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. The same dermatologist will be used to 
evaluate all subjects in the study. 
The intensity of any visual signs of ocular irritation will be recorded according to the grade of 
the reactions in the Ophthalmological Evaluation (Safety and Other Assessments). The 
 
 
 
 
 
 

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ophthalmologist is responsible for grading the reactions, their opinion on the classification of 
the ocular irritation scores is final. The same ophthalmologist will be used to evaluate all 
subjects in the study.
Any observed cutaneous or 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 the clinical expert, will these reactions and the consequences observed upon 
evaluation be documented as AEs.
6
INVESTIGATIONAL/STUDY PRODUCTS
For the purposes of this study, per International Conference on Harmonization (ICH) guidelines, 
and GSK policy, investigational product is defined as a pharmaceutical form of an active 
ingredient, a non-medicinal product (marketed or investigational), or a placebo, being tested or 
used as a reference (positive or negative control), in a clinical trial. This includes a product with 
a marketing authorization when used or assembled (formulated or packaged) in a way different 
from the approved form, or when used for an unapproved indication, or when used to gain 
further information about an approved use. 
6.1
Investigational/Study Product Supplies
The following study products will be supplied by the Clinical Supplies Department, GSK CH:
Table 6-1
Investigational/Study Product Supplies
Investigational Product
Reference Product
Product Name
Developmental Serum
Physiogel Calming Relief Anti-
Redness Serum
(Korean market place product)
Product 
Formulation Code 
(MFC)
Product Format
30 ml Bottle with piston pump
Dispensing Details
A kit will be dispensed to each subject containing 2 bottles 
Application 
Quantity
To be used as per normal home use application
Route of 
Administration
Topical dermal (facial) application
Application 
Instructions
Apply twice daily to freshly cleansed skin in place of your current serum and 
before your moisturizer
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.
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 Buds - For LAST 
 
 
 
 
 
 
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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 will be provided by GSKCH during the course of the study in time 
for study close out visit.
6.1.1
Dosage Form and Packaging
Both the developmental serum and the comparator serum will be supplied to the clinical site as 
labelled packaged bottles for dispensing by the site staff. The commercial bottles will have the 
commercial labels removed. 
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 
Both the investigational product and the reference product will be dispensed by qualified 
unblinded site personnel according to the randomization schedule. These staff members will 
not be involved in any safety or other aspects of the study that could be influenced by the 
knowledge of product a subject has been assigned to. An additional site member of site staff, 
should ensure the dispensing procedures are completed accurately.
Subjects will be assigned to products in accordance with the randomization schedule generated 
by an approved GSK CH vendor, prior to the start of the study, using validated software.
6.2
Administration
The first application of product will be under supervision at the study site at Visit 1 (Day1) 
following baseline subject self-assessment questions, dermatologist and ophthalmologist 
assessments and the LAST.
Subjects will be instructed to self-administer their assigned product per the usage instructions.
6.2.1
Dosing Errors
Dosing errors may result, in this study, from the administration or consumption of: 

the wrong product,

by the wrong subject, 

at the wrong time, 

or at the wrong dosage. 
Dosing errors occurring to a study subject are to be captured in the Case Report Form (CRF).  
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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. 
6.3
Investigational/Study Product Storage 
The investigator, or designee, will ensure that all 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 (as detailed on the clinical supplies 
checklist) 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. 
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 products must be received by a designated person at the study site, 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.
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 
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Subjects should return all products to the study site at the end of the study (LSLV) or before if 
a subject withdrawals/is withdrawn.
6.4.1
Destruction of Investigational/Study Product Supplies 
At the conclusion 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 investigational/study product accountability record for returned study 
products will then be completed. All study product (used and unused) for this clinical study will 
be returned for destruction to the GSK CH Clinical Supplies Department or designated vendor 
using the return instructions provided. 
6.5
Blinding and Allocation/Randomization
All subjects will be centrally randomized to one of the two 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.
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 particular 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 received). The study statistician, data 
management staff, other employees of the Sponsor and vendors acting on behalf of the sponsor, 
who may influence study outcomes will also be blinded to the product allocation. 
To ensure the examiners remain blinded throughout the study, staff involved in the preparation 
and dispensing of study products will work in a separate area. The examiners are not permitted 
in any area where study product is stored, dispensed, or in use. 
Subjects will be instructed not to remove study products from the opaque bags outside of the 
dispensing room, while at the study site. Dispensing staff will not be involved in any safety 
assessment procedures during the study.  
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. 
 
 
 
 
 
 

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6.7
Subject Compliance
Study products will be administered under the supervision of investigator site personnel for the 
first application.  
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. Any additional details relevant to efficacy or safety must be reviewed by the 
investigator (or suitably qualified designee) with the subjects, and transcribed to the CRF 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 re-instructed in the correct usage 
requirements and diary completion as needed.
6.8
Concomitant Medication/Treatment(s)
Any medications, treatments or vaccines (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 concomitant 
medication/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 signing the 
informed consent form will be documented as concomitant medication/treatments.
Subjects should abstain from all concomitant treatments, except for contraceptives and those 
used for the treatment of adverse events.
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. 
 
 
 
 
 
 

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7.2
Lost to Follow up
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. 
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 or not the subject 
wishes to and/or should continue in the study. 
Final safety assessments should be carried out wherever possible when the subject returns to 
the study site, which will include the following:

Dermatologist assessment of cutaneous irritation

Ophthalmologist assessment of ocular irritation

Subject self-assessment questions
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 request that the subject return for a final visit, and follow-up with the 
subject regarding any unresolved adverse events (AEs), and follow-up assessments 
(dermatologist and ophthalmologist assessments and 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. 
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 also 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 section.
Adherence to the study design requirements, including all procedures are essential and required 
for study conduct.
8.1
Visit 1 (Day 1) Screening/Baseline
Screening and baseline procedures will be conducted by the Investigator, or suitably qualified 
designee.
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 
 
 
 
 
 
 

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the study. Two copies of the informed consent form (ICF) signature page 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 signature page 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 captured on the Informed 
Consent Form (signature page) as this is the point at which all Adverse Events will be captured 
from. The date and time of consent will be transcribed into 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.
e-Consent is a tool that assists in the consent process by using multimedia components delivered 
by an electronic system (e.g. iPad/tablet). The multimedia components consist of video, audio, 
knowledge review, dictionary and electronic signature.
The site staff can use the system to consent the subject with the benefit of helping the subject 
understand the research they are taking part in and to control the consent process.
The system will allow for a copy of the consent to be printed and given to the subject and for 
consent documents to be retained by the site in PDF format.
A GSK CH approved vendor will be used to provide the system and training and a help desk 
will be provided as needed.
If the country and/or site does not have approval to use the e-Consent system, or the subject 
does not want to use the e-Consent system, then the conventional paper process will be followed. 
It is possible to use the e-Consent system to educate the subject while using paper to obtain 
signatures.
After signing the ICF, subjects will undergo the screening assessments to confirm that they 
meet all 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.
8.1.2
Demographics
The following demographic information will be recorded in the CRF: year of birth, gender and 
race. Fitzpatrick skin type assessment (Appendix 2 - Fitzpatrick Skin Type Grading) will also 
be conducted by a trained evaluator and recorded on the CRF.
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 and Prior Medication/Treatment
Details of relevant medical and surgical history (in the last year), including allergies or drug 
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Prior medications/treatments, including prescription and non-prescription drugs, dietary 
supplements and herbal remedies, taken in the last 30 days and prior to signing the informed 
consent form, will be documented in the CRF.
8.1.4
Inclusion/Exclusion Criteria
Inclusion and exclusion criteria information will be documented in the CRF.
8.1.5
Subject self-assessment
Subjects will be asked to answer the self-assessment questions as per section Safety and Other 
Assessments prior to the LAST, randomization and any product application (baseline).
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.
8.1.6
Dermatologist Assessment
A qualified dermatologist will visually assess the subject at Visit 1 (baseline) prior to 
randomization to determine their 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, 
2008).  For inclusion into the study each subject should have a dermatologist signs and 
symptoms cutaneous irritation score of equal to or greater than 0.5 (very slight) for erythema 
and a score of greater than or equal to 0.5 (very slight) for dryness, a score of 0 (none) or 0.5 
(very slight) for scaling and 0 (none) or 0.5 (very slight) for edema. Any attribute score of 3 
(severe) will exclude the subject from the study as this is not the intended population for the 
product. 
The intensity of any visual signs of dermal irritation will be recorded according to the grade of 
the reactions according to 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. 
Any subject with a score of 3 (severe) in any attribute will exclude the subject from the study, 
as this does not reflect the target population for the product.
8.1.7
Ophthalmologist Assessment
A qualified ophthalmologist will assess the subject at Visit 1 (baseline) prior to randomization 
to determine their eligibility to continue in the study. This will ensure the subject is free of any 
preexisting ophthalmological pathology prior to using the study products. (Edward, 2008). For 
inclusion into the study each subject should have a total ocular irritation score of 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.
 
 
 
 
 
 

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8.1.8
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 or 0.9M NaCl) will be applied concurrently to either the 
right or the left nasolabial fold and corresponding infraorbital cheek of the subject, according 
to a randomization scheme provided by the Sponsor, using a cotton-tipped swab. After dipping 
the swab into each of the test substances, each will be applied to the upper end of the nasolabial 
fold, about 3 cm under the inner corner of the eye, and moved in a rotating motion of the swab 
across the infraorbital part of the cheek to about 3 cm under the outer corner of the eye and back 
along the fold of the nostrils and back, and along the nasolabial fold to the side of the corner of 
the mouth and back, ending at the point where the application started. The complete movement 
will be repeated once more. The applied test substances should not extend beyond this area. For 
each application a fresh swab will be used.
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 over the screened subjects. 
Subjects will be asked to report any sensations of discomfort 2-3 minutes and 5-6 minutes after 
application on a 4-point scale (Christensen et al., 1995; 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. 
At this time or after 6 minutes, the subject will be instructed to remove the solution 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 greater 
than or equal to 2 in the difference between lactic acid and saline 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 to start but should intensify up to 5-6 minutes. 
The test will be suspended after 6 minutes if no local sensation is reported, or immediately upon 
any subject reported score of 3. At this time, or after 6 minutes, the subject will be instructed to 
remove the solution by thoroughly washing with water and drying their face with a paper towel.
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.
8.1.9
Subject Eligibility
The investigator and/or medically qualified designee will review inclusion/exclusion criteria, 
medical history, prior medications 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 
and any Concomitant Medication/Treatment(s) requirements of the protocol.
8.1.10
Randomization
Each eligible subject will be randomized to one of the two serum products under investigation 
and given instructions on how to apply the product.
8.1.11
Supervised Product Application
Sufficient product will be provided to last the complete study period. Subjects will use the 
product at home, twice a day during the study period 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. 
Subjects will be dispensed a paper diary alongside their assigned product to be completed at 
home to record product use. 
Spontaneous reporting of adverse events 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.
8.2
Visit 2/Day 21 (Final Visit)
Any changes in concomitant medication or non-drug treatments/procedures will be documented 
in the CRF. 
Spontaneous reporting of adverse events 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.
8.2.1
Dermatologist Assessment
A final assessment by the same dermatologist, will be completed at the end of the 21 (+2) day 
product use period (Visit 2). 
The intensity of any visual signs of dermal irritation will be recorded according to the grade of 
the reactions according to 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.
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. 
 
 
 
 
 
 

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8.2.2
Ophthalmologist Assessment
A final assessment by the same ophthalmologist, will be completed at the end of the 21 (+2) 
day product use period (Visit 2). 
The intensity of any visual signs of ocular irritation will be recorded according to the grade of 
the reactions according to the Objective 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.
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 the 
qualified ophthalmologist, will these reactions and the consequences observed upon evaluation 
be documented as AE’s.
8.2.3
Subject self-assessment
Subjects will be asked to answer the self-assessment questions as per section Safety and Other 
Assessments at the end of the 21 (+2) day product use period. Subject responses will be directly 
entered into the CRF by site staff. 
8.3
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. 
8.4
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 conclusion 
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. 
8.5
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 assessments). If needed, additional examinations may be carried out at such visits.
 
 
 
 
 
 

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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 infeasible 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 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 Study Procedures 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 
based on erythema, dryness, scaling and edema.  The following grades and their respective 
numerical equivalent scores will be used to record the response observed at the time of clinical 
examination.
Table 9-1
Dermatological Evaluation
Dermal responses that can be accurately described by a dermal response score will not be 
considered adverse events. Only in the case of unusual reactions in the opinion of the 
dermatologist will these reactions and the consequences observed upon evaluation be 
documented as AE’s.
Any subject with a score of 3 (severe) in any attribute at the Screening visit (Visit 1) will exclude 
the subject from the study, as this does not reflect the target population for the product.
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.
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)
 
 
 
 
 
 

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Table 9-2
Ophthalmological Evaluation
Ocular responses that can be accurately described by an ocular irritation score will not be 
considered adverse events. Only in the case of unusual reactions in the opinion of the 
ophthalmologist will these reactions and the consequences observed upon evaluation be 
documented as AE’s.
9.2.3
Subject Self-Assessment of Signs and Symptoms of Cutaneous and 
Ocular Irritation
Subjects will be instructed to self-assess any sensations of cutaneous or ocular discomfort that 
they are currently experiencing per the below scales. 
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)
10
ADVERSE EVENT AND SERIOUS ADVERSE EVENTS
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), 
whether or not considered related to the study product, including any washout or lead-in product 
(or medical device).
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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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.

The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be 
reported as AE if they fulfill the definition of an AE. Also, "lack of efficacy" or 
"failure of expected pharmacological action" constitutes an AE.
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) 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.
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).
 
 
 
 
 
 

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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.
10.3
Reporting of Adverse Events
10.3.1
Reporting Period 
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.
 
 
 
 
 
 

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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. 
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. 
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, with the exception of the subject number, will be 
redacted on the copies of the medical records prior to submission to GSK CH.
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 
 
 
 
 
 
 

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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 
hours after study site personnel learn of the event. The investigator will submit any updated 
SAE data to the sponsor, immediately and under no circumstance should this exceed 24 
hours of it being available. The GSK CH Study Manager should also be notified of the situation 
by telephone or email.
Email Serious Adverse Events to:
The GSK CH Study Manager or designee will be responsible for forwarding the SAE form to 
the Case Management Group, Global Clinical Safety and Pharmacovigilance mailbox 
(
).
The initial report will be followed up with more information as relevant, or as requested by the 
GSK CH study manager.
10.5
Evaluating Adverse Events 
10.5.1
Assessment of Intensity
The investigator or medically qualified designee will make an assessment of intensity for each 
AE 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 and 
not interfering with everyday activities.

Moderate:  An event that is sufficiently discomforting to interfere with normal everyday 
activities
 
 
 
 
 
 
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
Severe:  An event that prevents normal everyday activities. 
NOTE: An AE that is assessed as severe should not be confused with an SAE. Severe is a 
category utilized for rating the intensity of an event; and both non-serious AEs and SAEs can 
be assessed as severe. For example, a headache may be severe (interferes significantly with the 
subject's usual function) but would not be classified as serious unless it met one of the criteria 
for SAEs, listed above. An event is defined as ‘serious’ when it meets at least 1 of the predefined 
outcomes as described in the definition of an SAE, NOT when it is rated as severe.
10.5.2
Assessment of Causality
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. For each AE (serious and non-serious), the investigator must provide an 
assessment of causality on the AE CRF page and the SAE form (subject to the classification of 
the AE). The investigator will also document in the medical notes that he/she has reviewed the 
AE and assessed causality, where applicable. 
A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
Generally, the facts (evidence) or arguments to suggest a causal relationship should be provided.
The investigator will use clinical judgment to determine the relationship and will also consult 
the Safety Statement and/or Product Information, for marketed products, in the determination 
of his/her assessment.  Alternative causes, such as underlying disease(s), concomitant therapy, 
other risk factors, and the temporal relationship of the event to the study product will be 
considered and investigated.
For each AE/SAE, the investigator must document in the medical notes that he/she has reviewed 
the AE/SAE and has provided an assessment of causality.
The investigator’s assessment of causality must be provided for all AEs (serious and non-
serious); the investigator must record the causal relationship in the CRF, as appropriate, and 
report such an assessment in accordance with the SAE reporting requirements if applicable.
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 CH. The investigator may change his/her opinion of 
causality in light of follow-up information and send an SAE follow-up report with the updated 
causality assessment. 
10.6
Follow-up of Adverse Events 
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 (serious and non-serious) 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 CH to elucidate 
as fully as possible the nature and/or causality of the AE. This may include additional laboratory 
tests or investigations, histopathological examinations, or consultation with other health care 
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New or updated information will be recorded on the AE CRF page and on the SAE form (subject 
to the classification of the AE).
The investigator will submit any updated SAE data to GSK CH within 24 hours of receipt of 
the information.
Investigators are not obliged to actively seek AEs in former subjects.  However, if the 
investigator learns of a SAE, including death, at any time after a subject has been discharged 
from the study, and considers the event reasonably related to the study product or study 
participation, the investigator will promptly notify GSK CH by emailing the information to the 
GSK CH Clinical Operations Safety Reporting email box (
). 
The GSK CH Study Manager or designee will be responsible for forwarding the information to 
the Case Management Group, Global Clinical Safety and Pharmacovigilance group mailbox at 
GSK (
).
The investigator will submit any updated SAE data to GSK CH within the designated reporting 
time frames.
10.7
Withdrawal Due to an Adverse Event 
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, according 
to the definition of an AE noted earlier, and recorded on the appropriate AE CRF page. 
When a subject withdraws because of an SAE, the SAE must be reported in accordance with 
the reporting requirements defined.
10.7.1
Sponsor’s Reporting Requirements to Regulatory Authorities and 
Ethics Committees
GSK CH 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 GSK CH is essential so that legal obligations and 
ethical responsibilities towards the safety of subjects are met.
GSK CH will comply with country specific regulatory requirements relating to safety reporting 
to the regulatory authority, IRB/EC and investigators.
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
(SUSAR) according to local regulatory requirements and sponsor policy and forwarded to 
investigators as necessary.
An investigator who receives an investigator safety report describing a SAE or other specific 
safety information e.g. summary or listing of SAE from the sponsor will review and then file it 
along with the Investigator’s Brochure in the investigator study master file, and will notify the 
IRB/IEC, if appropriate according to local requirements.
10.8
Pregnancy
10.8.1
Time Period for Collecting Pregnancy Information
Pregnancy information will be collected on all pregnancies reported while a female subject is 
participating in the study from the signing of informed consent until 5 days after last 
administration of study product.
 
 
 
 
 
 
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10.8.2
Action to be Taken if Pregnancy Occurs
The investigator will record pregnancy information on the appropriate form scan and e-mail it 
to the GSK CH Clinical Operations Safety Reporting email box (
) within 24 hours of learning of the subject becoming pregnant. The GSK CH 
Study Manager or designee will be responsible for forwarding the pregnancy form to the Case 
Management 
Group, 
Global 
Clinical 
Safety 
and 
Pharmacovigilance 
mailbox 
(
). Original pregnancy information forms will be retained in the 
investigator study master file. 
The subject will be followed to determine the outcome of the pregnancy. Information on the 
status of the mother and infant / neonate (including concomitant medications taken by the 
mother during the pregnancy) will be forwarded by the investigator to the GSK CH Clinical 
Operations Safety Reporting email box and the GSK CH Study Manager or designee will 
forward this information to the Case Management Group, Global Clinical Safety and 
Pharmacovigilance group mailbox at GSK (
). 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, 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 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, dispensing records, subject 
files and records, etc.) which contain the source of data recorded in the CRF should be specified.
The CRF 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.
 
 
 
 
 
 
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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. 
11.2
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.
Adverse events will be coded using Medical Dictionary for Regulatory Activities (MedDRA) 
and any concomitant medications terms (if applicable) using an internal validated medication 
dictionary, GSKDrug.  
11.2.1
Data Queries
Programmed edit checks will be generated automatically, as the data are being entered into the 
system. Reports and listings on the CRF data will also be run, in addition to the queries already 
programmed and generated by the system, to raise manual queries as needed for site 
clarification or correction. The Clinical Dictionary Development and Management Group will 
raise queries as needed on safety data to code the terms (AEs and Drugs or concomitant 
medication) appropriately. 
The study monitor will perform ongoing review the of the CRFs in accordance with the 
monitoring plan, to confirm that data entered into the CRF by authorized site personnel are 
accurate, complete, and verifiable from source documents; that the safety and rights of 
participants are being protected; and that the study is being conducted in accordance with the 
currently approved protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements.
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. The study monitor can also 
run reports and listings on the CRFs, to raise manual queries as needed for site clarification or 
correction.
11.3
Processing Patient Reported Outcomes
Paper based patient reported outcome (PRO) data may be collected from a diary, questionnaires, 
or other specified document, etc. and entered into the data management system (DMS).  
Electronic Patient reported outcome (ePRO) data may be collected using electronic devices and 
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All PRO source data should be reviewed by the Study Staff and the Study Monitor in order to 
ensure accurate transcription of data and that any potential AEs or concomitant medications 
reported on these documents are discussed with the subject and transcribed accurately to the 
CRF and/or DMS.  PROs that are classed as source data will be retained by the investigator and 
true/certified copies may be sent to a designated vendor or GSK CH as required.
To protect the privacy of subjects, no Personal Information (PI) (including the subject's name 
or initials or birth date) is to be recorded on any PRO/ePRO that will be forwarded to GSK CH 
or third-party Vendor.
In this study subjects will be provided with a diary card to complete during the home use period, 
following first supervised product use and diary completion. Subject self-assessment responses 
will be collected directly in the CRF.
12
STATISTICAL CONSIDERATIONS AND DATA ANALYSES
12.1
Sample Size Determination
A sufficient number of subjects will be screened (approximately 180) to randomize 90 subjects 
to ensure that at least 60 subjects (30 per arm) complete the study. It is deemed that 30 subjects 
per arm are considered sufficient to assess the primary endpoint of the dermatologist assessment 
of signs and symptoms of cutaneous irritation total score. 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 which mandates an investigational 
product be tested on at least 30 subjects.
12.2
Statistical Methods and Analytical Plan
Additional details of the proposed statistical analysis will be documented in the statistical 
reporting and analysis plan (RAP), which will be written by a GSK approved vendor following 
finalization of the protocol and prior to study unblinding/analysis (as appropriate).
12.2.1
Definition of Analysis Populations
The Safety population will comprise all randomized subjects who receive at least one dose of 
the study product. This population will be based on the product the subject actually received.
All assessments of safety will be based on the safety population. 
12.2.2
Exclusion of Data from Analysis 
Exclusion of any data from the analyses will be determined during a Blind Data Review 
Meeting prior to database lock. Any reasons for exclusion from an analysis population will be 
listed, if applicable. No data will be excluded from any analysis post database lock. No decisions 
regarding data exclusions from any analysis will be made post database lock.
12.2.3
Demographic and Baseline Characteristics
Age will be summarized using descriptive statistics such as means, medians and standard 
deviations. Gender, race and Fitzpatrick skin type will be summarized using frequency counts 
and percentages for the safety population.
12.2.4
Study Drug/Product Compliance
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12.2.5
Prior and Concomitant Medications
Prior medications, concomitant medications and significant non-drug therapies taken during 
treatment will be listed for the safety population. 
12.2.6
Primary Analysis(es) 
The primary endpoint will be the change from baseline (prior to any product application) in 
dermatologist signs and symptoms of cutaneous irritation total score following 21 (+2) days of 
product use. The primary analysis will be performed using the Safety population.
The dermatologist assessment of signs and symptoms of cutaneous irritation total score will be 
calculated as the sum of the individual dermal response attributes (erythema, dryness, scaling, 
and edema). The change from baseline in the total score will be summarised by number and 
percentage of subjects by visit for each treatment group.  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.
12.2.7
Secondary Analysis(es)
The key secondary endpoint will be the change from baseline (prior to any product application) 
in the ophthalmologist signs and symptoms of ocular irritation total score following 21 (+2) 
days of product use. 
The ophthalmologist assessment of signs and symptoms of ocular irritation total score will be 
calculated as the sum of the individual ocular response scores (eczema of the eyelid, 
conjunctivitis, follicles, chemosis conjunctivae). The change from baseline in the total score 
will be summarised by number and percentage of subjects by visit for each treatment group. 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 and 21 (+2) days of product use.
All secondary analyses will be performed using the Safety population.
12.2.8
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.
12.2.9
Other Analysis(es)
No other analyses will be performed for this study. 
12.2.10
Handling of Dropouts and Missing Data 
Missing data will not be replaced or imputed. Dropouts will be included in analyses up to the 
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12.2.11
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 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.
 
 
 
 
 
 

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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 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 consent 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.
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. 
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 
 
 
 
 
 
 

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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.
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 
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Where permitted by local laws/regulations or institutional policy, some or all of these records 
can be maintained in a format other than hard copy (e.g. microfiche, scanned, electronic); 
however, caution needs to be exercised before such action is taken. 
The investigator must ensure that all reproductions are legible and are a true and accurate copy 
of the original and meet accessibility and retrieval standards, including re-generating a hard 
copy, if required.  Furthermore, the investigator must ensure there is an acceptable back-up of 
these reproductions and that an acceptable quality control process exists for making these 
reproductions.
The investigator must assure that the subject’s anonymity will be maintained.  On CRFs or other 
documents submitted to 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 for 25 years 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 serum at any time. 
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 CRFs 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
 
 
 
 
 
 

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3. ICH Topic E6(R2) Guideline for Good Clinical Practice, Nov 2016.
4. World Medical Association Declaration of Helsinki, 59th General Assembly, Seoul 2008.
5. Berardesca E, Farage M, Maibach H. Sensitive skin: an overview. Int J Cosmet Sci.2013 
Feb;35(1):2-8.
6. Birmingham, J. Clinical Aspects of Cutaneous Irritation and Sensitization, Toxicology and 
Applied Pharmacology 7:(54-59)
7. Christensen M, Klingman A M. An improved procedure for conducting lactic acid 
stinging tests on facial skin. J. Soc. Cosmetic. Chem. 1996; 47:1-11.
8. COSMETICS EUROPE: Guidelines for the Safety Assessment of a Cosmetic Product, 
2004.
9. De Groot A C, White IR, Flyvholm L MA, Lensen G & Coenraads, PJ. Formaldehyde-
releasers in cosmetics: relationship to formaldehyde contact allergy. Contact dermatitis 
2010; 62:2-17
10. Dooms-Goossens A. Cosmetics as causes of allergic contact dermatitis. Cutis 1993; 52: 
316-320
11. Edward, M. Jackson, and FMT Robillard Norman. "The controlled use test in a cosmetic 
product safety substantiation program." Journal of Toxicology: Cutaneous and Ocular 
Toxicology1.2 (1982): 117-132
12. European Commission (EC), Regulation No. 1223/2009
13. Farage, M. A., Katsarou, A. & Maibach, H. I. Sensory, clinical and physiological factors 
in sensitive skin: a review. Contact dermatitis 2006; 55:1-14.
14. Fitzpatrick TB, Pathak M, Parrish JA. Protection of human skin against the effects of the 
sunburn ultraviolet (290-320 nm). In: Fitzpatrick TB et al. (eds). Sunlight and man, 
normal and abnormal photobiological responses. Tokyo, p. 751-755.
15. Loretz LJ, Exposure data for cosmetic products: Facial cleanser, hair conditioner, and eye 
shadow. Food and Chemical Toxicology, 2008, 0278-6915, 46(5):1516
16. Lumelsky V J, Shur M S & Wagner S. Sensitive skin. Sensors Journal, IEEE. 2001; 1:41-
51
17. Lundov, M. D., Johansen, J. D., Carlsen, B. C., Engkilde, K., Menne, T. & Thyssen, J. P. 
Formaldehyde exposure and patterns of concomitant contact allergy to formaldehyde and 
formaldehyde-releasers. Contact dermatitis 2010; 63:31-36
18. National Health Surveillance Agency Brazil (ANVISA). Guideline for the Safety 
Evaluation of Cosmetic Products. Brasília; 2012.
19. Wilhelm KP, Surfactant-induced stratum corneum hydration in vivo: prediction of the 
irritation potential of anionic surfactants Journal of Investigative Dermatology, 1993, 
0022-202X, 101(3):310
20. Wilkinson, D. S., et al. “Terminology of contact dermatitis.” Acta Derm Venereol 50.4 
(1970): 287-292.
21. World Medical Association Declaration of Helsinki, 64th General Assembly, Fortaleza 
2013.
15
APPENDICES
15.1
APPENDIX 1 - ABBREVIATIONS
The following is a list of abbreviations that may be used in the protocol.
 
 
 
 
 
 

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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
N/A
not applicable
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
SOP
standard operating procedure
SRSD
single reference study document
SS
safety statement
UK
United Kingdom
UV
Ultraviolet
15.2
APPENDIX 2 – 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). 
Table 15-2
FITZPATRICK SKIN TYPE GRADING
Skin Type
Sunburn and Tanning History
 
 
 
 
 
 

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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)