A Proof of Concept (POC) Clinical Study to Evaluate the Appearance of Fine Lines and Wrinkles on a Developmental Cosmetic Moisturising Cream in Healthy Subjects Presenting Visible Signs of Ageing
Phase: NA
Conditions: Skin Aging
Sponsor: GlaxoSmithKline

Clinical Protocol
207468
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CONFIDENTIAL
SUMMARY INFORMATION



Title:
A Proof of Concept (POC) Clinical Study to Evaluate 
the Appearance of Fine Lines and Wrinkles on a 
Developmental Cosmetic Moisturising Cream in 
Healthy Subjects Presenting Visible Signs of Ageing.
Protocol Number:
207468
Sponsor:
GlaxoSmithKline Consumer Healthcare (GSKCH)
Trading Limited. 
St George’s Avenue, 
Weybridge, Surrey,
KT13 0DE, UK.
Tel: 
Product Name:
Fine Lines and Wrinkles Moisturising Cream
Development Phase:
N/A
Expert Advice Outside of Normal 
Working Hours:
Tel: 
Key Protocol Authors:
PRIMARY CONTACT
Clinical Research: 
, BSc (Hons), Dip.
GSKCH
St George’s Avenue, Weybridge, Surrey 
KT13 0DE
Tel: 
PRIMARY CONTACT
Clinical Study Manager:
, MSc
Tel: 
Biostatistician:
, MA
Clinical Supplies:
Medical Expert:
 MD, Ph.D.
Principal Investigator:
Stephan Bielfeldt (Dipl. Bio-Ing)
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Study Site Name & Address:
proDERM Institute for Applied 
Dermatological Research 
Kiebitzweg 2
22869 Schenefeld/Hamburg
Germany
Study Site Telephone Number:
Tel: 
Study Examiner(s):
To be assigned per site staff designation 
log at study start.


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PRINCIPAL INVESTIGATOR PROTOCOL AGREEMENT 
PAGE

I confirm agreement to conduct the study in compliance with the protocol and 
any amendments and according to the current International Conference on 
Harmonization of Technical Requirements for Registration of 
Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) 
guidelines.

I acknowledge that I am responsible for overall study conduct. I agree to 
personally conduct or supervise the described study.

I agree to ensure that all associates, colleagues and employees assisting in the 
conduct of the study are informed about their obligations. Mechanisms are in 
place to ensure site staff receives all appropriate information throughout the 
study.

I agree to conduct this study in full conformance with the laws and regulations 
of the country in which the research is conducted and the Declaration of 
Helsinki.
Investigator Name:
Investigator Qualifications:
Investigator Signature:
Date of Signature/ Agreement:
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Table of Content
SUMMARY INFORMATION...............................................2
PRINCIPAL INVESTIGATOR PROTOCOL AGREEMENT 
PAGE ..............................................................................4
Table of Content......................................................................5
PROCESS FOR AMENDING THE PROTOCOL...............9
PROTOCOL AMENDMENT PAGE ....................................10
SCHEDULE OF EVENTS .....................................................13
PROTOCOL SYNOPSIS FOR STUDY 207468 ...................14
1. INTRODUCTION...............................................................22
2. OBJECTIVES AND ENDPOINTS....................................24
3. STUDY PLAN .....................................................................25
3.1. Study Design.......................................................................25
3.2. Subject Restrictions ...........................................................28
3.3. Type and Planned Number of Subjects ............................30
3.4. Study Design and Dose Justification.................................30
4. SELECTION OF STUDY POPULATION AND 
WITHDRAWAL CRITERIA........................................32
4.1. Inclusion Criteria...............................................................32
4.2. Exclusion Criteria..............................................................33
4.3. Screening/ Baseline Failures..............................................35
4.4. Withdrawal/ Stopping Criteria .........................................35
4.5. Subject Replacement..........................................................36
4.6. Subject and Study Completion..........................................36
5. PRODUCT INFORMATION.............................................36
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5.1. Study Product.....................................................................36
5.2. Application Schedule .........................................................37
5.3. Application Modification...................................................38
5.4. Product Compliance ..........................................................38
5.5. Precautions.........................................................................38
5.6. Overdose.............................................................................38
5.7. Rescue Therapy..................................................................39
5.8. Product Assignment...........................................................39
5.8.1 Randomisation....................................................................39
5.8.2 Blinding...............................................................................40
5.8.3 Code Breaks........................................................................40
5.9. Packaging and Labelling ...................................................40
5.9.1. Accountability of Product.................................................41
5.9.2. Storage of Product ............................................................41
6. STUDY ASSESSMENTS AND PROCEDURES ..............42
6.1. Visit 1 - Screening Visit......................................................42
6.1.1 Telephone Screening ..........................................................42
6.1.2. Informed Consent .............................................................42
6.1.3. Demographics....................................................................43
6.1.4. Medical History and Concomitant Medication ...............43
6.1.5. Clinical Fitzpatrick Wrinkle Assessment in Periocular / 
Crow’s Feet Area ..............................................................43
6.2. Visit 2 - Baseline Visit Day 1..............................................44
6.2.1 USR- CliP High Resolution Images...................................44
6.2.2. DermaTOP Technique......................................................46
6.2.3 Transepidermal Water Loss (TEWL)...............................50
6.2.4. Corneometry Assessment..................................................50
6.2.5.Cutometer Assessment.......................................................52
6.3. Visit 3 (Day 15)...................................................................52
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6.4. Visit 4 (Day 29)...................................................................53
7. SAFETY ASSESSMENTS..................................................53
7.1. Definitions of an Adverse Event and Serious Adverse 
Event.................................................................................53
7.1.1. Adverse Events..................................................................54
7.1.2. Serious Adverse Events.....................................................55
7.2. Recording Adverse Events and Serious Adverse Events.56
7.3. Evaluating Adverse Events and Serious Adverse Events 56
7.4. Reporting Adverse Events and Serious Adverse Events..57
7.5. Follow-up of Adverse Events and Serious Adverse Events
..........................................................................................59
7.6. Collection of Pregnancy Information................................60
7.6.1. Time Period for Collecting of Pregnancy Information ...60
7.6.2. Action to be Taken if Pregnancy Occurs .........................60
8. DATA MANAGEMENT ....................................................60
8.1. Source Documents/ Data....................................................61
8.2. Electronic Case Report Form............................................61
8.3. Data Handling ....................................................................62
8.3.1. Data Queries......................................................................62
8.4. External Data .....................................................................62
9. STATISTICAL CONSIDERATIONS AND DATA 
ANALYSES ....................................................................63
9.1 Sample Size Determination.................................................63
9.2. General Considerations .....................................................63
9.2.1. Definition of Analysis Populations ...................................63
9.2.2. Exclusion of Data from Analysis ......................................64
9.2.3. Criteria for Evaluation .....................................................64
9.2.4. Handling of Dropouts and Missing Data .........................64
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9.3. Statistical Methods and Analytical Plan...........................64
9.3.1. Demographic and Baseline Characteristics.....................64
9.3.2. Primary Analysis(es).........................................................65
9.3.3. Secondary Analysis(es) .....................................................65
9.3.4. Safety Analysis(es).............................................................65
10. STUDY GOVERNANCE CONSIDERATIONS.............67
10.1. Posting of Information on Publicly Available Clinical 
Trials Registers................................................................67
10.2. Regulatory and Ethical Considerations, Including the 
Informed Consent............................................................67
10.3. Quality Control (Study Monitoring)...............................68
10.4. Quality Assurance............................................................68
10.5. Conditions for Terminating the Study............................69
10.6. Records Retention............................................................69
10.7. Provision of Study Results to Investigators, posting of 
Information on Publicly Available Clinical Trials 
Registers and Publication................................................70
11. REFERENCES..................................................................72
12. APPENDICES...................................................................74
12.1. Appendix 1 - Abbreviations and Trademarks................74
12.2. Appendix 2 - Fitzpatrick Skin Type................................76
12.3. Appendix 3 – Fitzpatrick Wrinkle Score (Crow’s Feet 
Area).................................................................................77
12.4. Appendix 4 – Texture Ranking Scale..............................79
12.5. Appendix 5 DermaTOPV3 Calculated Parameters.......79
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PROCESS FOR AMENDING THE PROTOCOL

Protocol modifications to ongoing studies which could potentially adversely affect the 
safety of subjects or which alter the scope of the investigation, the scientific quality of 
the study, the experimental design, dosages, duration of therapy, assessment 
variables, the number of subjects treated, or subject selection criteria are considered 
major/substantial amendments and must be made only after appropriate consultation 
between an appropriate representative of GSKCH and the investigator.
Details of amendments to the protocols should be recorded on the following page. 
Protocol modifications must be prepared by a representative of GSKCH.  All changes 
must be justified in the Reason for Amendment section of the following Protocol 
Amendment Page. Approval of amendments will be made by the original protocol 
signatories or their appropriate designees.
All major/substantial protocol modifications must be reviewed and approved by the 
appropriate Independent Ethics Committee (IEC) in accordance with local 
requirements, before the revised edition can be implemented. 
All non-substantial/ minor/ administrative amendments should be submitted to the 
IEC as per country specific requirements. In some countries pre-approval of a minor 
amendment is not required and will just be held on file by the sponsor and 
investigator.
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PROTOCOL AMENDMENT PAGE
Details of all amendments should be recorded in the table below. Affected sections should be listed in the table; the actual 
amendment/ change should be made in the relevant section of the main protocol. 
To highlight the change, the following features will be used: 
To add text: Use of CAPITAL LETTERS, BOLD AND UNDERLINE
To delete text: Use of Strikethrough e.g. strikethrough
Amendment 
No. & New 
Protocol 
Version No.
Type of Amendment
Reason for Amendment
Other 
Documents 
Requiring 
Amendment
Section(s) Amended 
PI Amendment 
Agreement
Signature & 
Date
Amendment 
No.:1
Non-Substantial/Minor    Correction to the details of 
the Corneometry data storage 
system
Clarified that Mascara and 
Lipstick is not to be worn on 
assessment days
Informed 
Consent   
Yes 
No
Safety 
Statement     
Yes 
No
CRF                   
Yes 
No
Section 6.2.4 
Corneometry 
Assessment
Section 3.2 Subject 
restrictions 
Lifestyle/Dietary on 
the day of the site 
visit.
Signature:
Protocol 
Version 
No.: 2.0
Substantial/ Major           
Date:
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Amendment 
No.:2
Non-Substantial/Minor    To delete the word ‘equal 
rating’ in the Inclusion 
Criteria to remove
Interpretation.
Informed 
Consent  
Yes 
No
Safety 
Statement     
Yes 
No
CRF                   
Yes 
No
Synopsis- study 
design
Synopsis- Diagnosis 
and main criteria for 
Inclusion
3.1 Study design
3.3 Type and 
Planned  number of 
subjects
3.4 Study design and 
dose justification
4.1 Inclusion 
Criteria
Signature:
Protocol 
Version 
No.:3.0
Substantial/ Major           
Date:
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Amendment 
No. & New 
Protocol 
Version No.
Type of Amendment
Reason for Amendment
Other 
Documents 
Requiring 
Amendment
Section(s) Amended 
PI Amendment 
Agreement
Signature & 
Date
Amendment 
No.:
Non-Substantial/Minor    
Informed 
Consent  
Yes 
No
Safety 
Statement     
Yes 
No
CRF                   
Yes 
No
Signature:
Protocol 
Version 
No.:
Substantial/ Major           
Date:
Amendment 
No.:
Non-Substantial/Minor    
Informed 
Consent   
Yes 
No
Safety 
Statement     
Yes 
No
CRF                   
Yes 
No
Signature:
Protocol 
Version 
No.:
Substantial/ Major           
Date:
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SCHEDULE OF EVENTS
Procedure/ Assessment
Visit 1
Day -3  
Visit 21
Day 1
Visit 31
Day 15
(+/- 24 hrs)
Visit 41
Day 29
(+/- 24 hrs)
Screening / 
Washout
Baseline
Treatment
Week 2
Treatment
Week 4
Treatment
Informed consent
X
Demographics
X
Medical History
X
Current / Concomitant medication
X
X
X
X
Adverse Events
X
X
X
Fitzpatrick Skin Type Assessment (Appendix 2)
X
Diary Review (Compliance)4
X
X
X
Continued Eligibility
X
X
X
Clinical Fitzpatrick Wrinkle Score in Periocular / 
Crow’s Feet Area (Appendix 3)3
X
X
X
X
Inclusion / Exclusion Criteria
X
X
Subject Eligibility6
X
X
Study Cleanser and Diary Dispensing
X
Randomisation2
X
USR- CliP High Resolution Images Left and 
Right Side of Face 3,5,7
X
X
DermaTOP Measurement3 Periocular / Crow’s 
Feet Area
X
X
X
TEWL Measurement3 in Sub-ocular/ Cheek Area
X
X
X
Corneometer Measurement3 in Sub-ocular/ 
Cheek Area
X
X
X
Cutometer Measurement3 in Sub-ocular/ Cheek 
Area
X
X
X
Test Product(s) Dispensing
X
Supervised Test Product Application
X
X
Test Product, Study Cleanser and Diary Return
X
Subject Discharge from Study
X
1.
On the day of site visit, subjects will be instructed to cleanse their face in the morning with tap water only and not to apply the test product or control. Measurements and assessments will 
be performed at least 12 hours after the last application of test products.
2.
Subjects to be randomised to one of three treatment groups: test product/positive control, test product/no treatment or positive control/no treatment at the baseline visit. 
3.
Subjects will be acclimatised in a controlled environment (temperature 20-22ºC, relative humidity between 40-60%) for a period of at least 30 minutes before the clinical and instrumental 
assessments are performed (EEMCO, 1997). 
4.
Diary to be reviewed by investigator or designee to confirm and encourage subject compliance.
5.
At the end of the study, a blinded lay panel will assess all of the high resolution images for Texture by texture ranking (Appendix 4).
6.
Inclusion criteria 7b to be reviewed at Screening and Baseline.
7.
A 30 minute waiting time will occur in an acclimatised room after the USR-CliP High Resolution Images.
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PROTOCOL SYNOPSIS FOR STUDY 207468

Brief Summary
This is a single-site, 3-arm, randomised, evaluator-blind, positive controlled (Olay 
ProX Wrinkle Smoothing Cream) and no-treatment controlled split-face POC study to 
evaluate the cosmetic appearance of fine lines and wrinkles delivered following 4
weeks of twice-daily application of the test product in healthy subjects presenting 
visible signs of ageing.  
It is hypothesised that the test product, which contains humectants to moisturise the 
stratum corneum (SC), will help to reduce the appearance of fine lines and wrinkles 
caused by skin dryness. It is also hypothesised that by moisturising the skin and 
depositing lipids on the skin surface, that skin elasticity and barrier function will also 
be improved.
The chosen application site for the treatment period is the face, to include the 
Periocular / Crow’s Feet Area for fine lines and wrinkles, the whole face for texture, 
and the Sub-ocular/ Cheek Area for barrier function, hydration and elasticity. There 
are three treatment groups included in this study; Test Product/ No Treatment, Test 
Product/Positive Control and Positive Control/No Treatment. Treatment groups will 
be further randomised to which side of the face treatment is to be applied.  
The objective of this POC clinical study is to evaluate the cosmetic appearance of fine 
lines and wrinkles delivered following 4 weeks of twice-daily application of the test 
product compared to no treatment in healthy subjects presenting visible signs of 
ageing. 
To measure the appearance, clinical and instrumental assessments will be performed 
throughout the study:  clinical assessments of fine lines and wrinkles by clinical 
Fitzpatrick wrinkle score in Periocular / Crow’s Feet Area, clinical assessments of 
texture by ranking high resolution images by a lay panel, instrumental assessments of 
fine lines and wrinkles by DermaTOP, skin barrier function measured by 
Transepidermal Water Loss (TEWL) (using a Tewameter), skin moisturisation using 
a Corneometer, and elasticity using a Cutometer.
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Objectives and Endpoints
Objectives
Endpoints
Primary
Evaluation of wrinkle dimensions 
(change from baseline) of test product 
compared to no treatment on the 
Periocular / Crow’s Feet Area.  
DermaTOP parameter Ra at 4 weeks.
Secondary
Evaluation of wrinkle dimensions 
(change from baseline) of test product 
and positive control compared to no 
treatment in the Periocular / Crow’s Feet 
Area.  
DermaTOP parameter Ra at 2 weeks and 
4 weeks (positive control only)
DermaTOP parameters Rz, Sa and Stm at 2 
and 4 weeks
Clinical Fitzpatrick Wrinkle Score at 2 
and 4 weeks
Evaluation of skin moisturisation (change 
from baseline) of test product and 
positive control compared to no treatment 
on the Sub-ocular/ Cheek Area. 
Instrumental Corneometer values at 2 and 
4 weeks
Evaluation of texture (change from 
baseline) of test product and positive 
control compared to no treatment on the 
full face. 
Texture ranking at 4 weeks
Evaluation of skin elasticity (change 
from baseline) of test product and 
positive control compared to no treatment 
on the Sub-ocular/ Cheek Area. 
Instrumental Cutometer parameters R5 
and R7 at 2 and 4 weeks
Evaluation of skin barrier (change from 
baseline) of test product and positive 
control compared to no treatment on the 
Sub-ocular/ Cheek Area. 
Instrumental Trans-Epidermal Water 
Loss (TEWL) values at 2 and 4 weeks
To evaluate the general safety of the 
study products
Assessment of frequency and severity of 
Adverse Events (AEs)
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Study Design
Overall Design
This is a single-site, 3-arm, randomised, evaluator-blind, positive controlled (Olay 
ProX Wrinkle Smoothing Cream) and no-treatment controlled split-face POC study to 
evaluate the cosmetic appearance of fine lines and wrinkles provided by 4 weeks of 
twice-daily application of the test product in healthy subjects presenting visible signs 
of ageing.
Subjects will give their written consent prior to any study procedures taking place.
At the Screening Visit, only healthy female subjects aged 30 to 65 (inclusive), with a 
Fitzpatrick phototype I-IV, a visual Clinical Fitzpatrick Wrinkle Score of 3-6 in the 
Periocular / Crow’s Feet Area with an equal rating on both sides of the face 
(Appendix 3), with self-reported sensitive skin will be considered eligible to continue 
in the study. 
Eligible subjects will undergo a 3 day washout period, where they will be asked to 
avoid using any other skin care products (moisturisers, lotions, creams, soaps, 
cleansing products, foundations etc.) on their face from the screening visit until Visit 
2 (Day 1) other than the study cleanser provided (SimpleTM Kind to Skin Moisturising 
Facial Wash™). Subjects will be asked to use the cleanser mornings and evenings in 
the washout period and during the study. On clinic days, subjects will use the cleanser 
in the evenings only and wash their face in the morning with tap water.
Subjects successfully completing the washout phase and who continue to be eligible,
will have their wrinkles assessed using the Clinical Fitzpatrick Wrinkle Score.  
Subjects who meet all the inclusion/exclusion criteria will be randomised to one of 
three treatment groups: test product/positive control, test product/no treatment or 
positive control/no treatment at the baseline visit. Product application within 
treatment group will be further randomised to either the right or left side of the face.
Diary Cards will be provided and reviewed at each site visit by the Investigator or 
designee to confirm and encourage subject compliance.  Subjects will be required to 
                                               
™Simple Kind to Skin Moisturising Facial Wash is a trademark of Unilever.
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complete the diary card every day to record application of test and study cleanser 
products.
Subjects will be instructed to apply each test product to the assigned side of the face, 
as applicable, (approximately 2 mg / cm2) twice-daily (morning and evening, 
approximately 8-12 hours apart), for 4 weeks (28 days).  Subjects will return to the 
site on Day 15 (Visit 3) and 29 (Visit 4) without applying the test product at home 
that morning.
After randomisation, subjects who consent will have high resolution images taken on 
the left and right side of their face. Instrumental measures will follow in the following 
order: DermaTOP (Periocular / Crow’s Feet Area), TEWL (Sub-ocular/ Cheek Area); 
Corneometer (Sub-ocular/ Cheek Area); Cutometer (Sub-ocular/ Cheek Area). The 
same schedule of events (except randomisation and high resolution photos) will be 
repeated for Day 15 (Visit 3). Day 29 (Visit 4) will be a repeat of Visit 2 (Day 1) 
(except randomisation).
Prior to all instrumental measurements and clinical assessments, subjects will be 
acclimatised in a controlled environment (temperature 20-22ºC, relative humidity
between 40-60%) for a period of at least 30 minutes [EEMCO, 1997].
On Day 1 (Visit 2) and Day 15 (Visit 3) on-site application of product will be 
supervised by the study site staff and will be performed only after the clinical and 
instrumental measurements are completed.
After the study has completed, all of the high resolution images will be evaluated by 
blinded lay persons to rank the appearance of texture.  
Visit 1 - Screening / Washout Visit
1. Informed consent
2. Demographics
3. Medical History
4. Current / Concomitant medication
5. Fitzpatrick Skin Type assessment (Appendix 2)
6. Clinical Fitzpatrick Wrinkle Score (Appendix 3)
7. Inclusion / Exclusion Criteria
8. Subject Eligibility
9. Study Cleanser and Diary Dispensing
Visit 2 - Baseline Visit
The following assessments will be conducted in the order written:
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1. Current / Concomitant medication
2. Adverse Events 
3. Diary Review (Compliance)
4. Continued Eligibility
5. Clinical Fitzpatrick Wrinkle Score (Appendix 3)
6. Inclusion / Exclusion Criteria
7. Subject Eligibility
8. Randomisation
9. High Resolution Photos for Texture Assessment (Appendix 4)
10. DermaTOP Assessment
11. TEWL Assessment
12. Corneometer Assessment
13. Cutometer Assessment
14. Test Product(s) Dispensing
15. Supervised Test Product Application
Visit 3- Day 15 (Week 2)
The following assessments will be conducted in the order written:
1. Current / Concomitant medication
2. Adverse Events 
3. Diary Review (Compliance)
4. Continued Eligibility
5. Clinical Fitzpatrick Wrinkle Score (Appendix 3)
6. DermaTOP Assessment
7. TEWL Assessment
8. Corneometer Assessment
9. Cutometer Assessment
10. Supervised Test Product Application
Visit 4 – Day 29 (Week 4)
The following assessments will be conducted in the order written: 
1. Current / Concomitant medication
2. Adverse Events
3. Diary Review (Compliance)
4. Continued Eligibility
5. Clinical Fitzpatrick Wrinkle Score (Appendix 3)
6. High Resolution Photos for Texture Assessment (Appendix 4)
7. DermaTOP Assessment
8. TEWL Assessment
9. Corneometer Assessment
10. Cutometer Assessment
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11. Test Product, Subject Cleanser and Diary Return
12. Subject Discharge from Study
Type and Planned Number of Subjects

Approximately 90 healthy subjects will be screened to randomise at least 72 subjects 
to ensure 66 subjects complete the entire study. This will ensure approximately 44 
subjects per treatment arm (test product, positive control, no treatment) or 22 per 
treatment group (test product/no treatment, test product/positive control, positive 
control/no treatment).
The sample size is based on clinical considerations.  With 40 subjects, a difference 
between test product and no treatment in the change from baseline in Ra of at least 
46% of the magnitude of the within-subject standard deviation of the difference 
would be detectable at two-sided alpha=0.05 with approximately 80% power.
Diagnosis and Main Criteria for Inclusion
Healthy female volunteers, aged 30 to 65 (inclusive) with a Fitzpatrick phototype 
score of I-IV, presenting visible signs of ageing with a visual Clinical Fitzpatrick 
Wrinkle Score of Score 3-6 in the Periocular / Crow’s Feet Area with an equal rating
on both sides of the face (Appendix 3), with self-reported sensitive skin will be 
considered eligible to continue in the study. 
Product Information
Test Product 
Reference Product 
Product Name 
Developmental Cosmetic 
Moisturising Cream 
Olay ProX Wrinkle 
Smoothing Cream
Product Formulation 
Code (MFC)
Commercially Available 
(UK)
Application Quantity
approx. 2 mg /cm2
approx. 2 mg /cm2
Route of Application
Dermal Topical
Dermal Topical
Application Instructions
Dispense two pumps of 
product (equating to 
approximately 0.6 mL) 
onto your fingertips and 
apply evenly to the 
randomly assigned side of 
the face, to include, the 
crow’s feet area, cheek, 
Subjects will be instructed 
to apply a pea-sized amount 
of the positive control 
product (equating to 
approximately 0.5g) onto 
your fingertips and apply 
evenly to the randomly 
assigned side of the face, to 
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CCI

forehead and chin  twice 
daily, (morning and 
evening), after cleansing. 
Daily applications should 
be approximately 8-12 
hours apart.
Subjects will be reminded 
that as with all facial skin 
care products, care should 
be taken to avoid getting 
into the eyes. If contact 
does occur, then rinse 
thoroughly with water.
include the crow’s feet area, 
cheek, forehead and chin , 
twice daily (in the morning 
and evening), after 
cleansing. 
Daily applications should be 
approximately 8-12 hours 
apart.
Subjects will be reminded 
that as with all facial skin 
care products, care should 
be taken to avoid getting 
into the eyes. If contact does 
occur, then rinse thoroughly 
with water.
Other items to be supplied by the Clinical Supplies Department, GSKCH:
Name of Item
Purpose
SimpleTM Kind to Skin Moisturising 
Facial Wash
Study Cleanser (Subjects will be asked to 
use the study cleanser mornings and 
evenings in the washout period and 
during the study. On the clinic days, 
subjects will use the cleanser in the 
evenings only and to wash their face in 
the morning with tap water).
Statistical Methods
A formal statistical analysis plan (SAP) will be prepared by GSKCH prior to database 
finalisation.
All efficacy analyses will be performed on the intent to treat (ITT) population defined 
as all subjects randomised with at least one post-baseline study assessment. 
Additional analyses will be performed using the per-protocol (PP) population defined 
as all subjects in the ITT population without a major protocol violation.  All major 
protocol violations, including treatment use compliance, will be identified prior to 
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database finalisation. Safety analyses will be based on the safety population defined 
as all subjects with at least one product application on either side of the face.
Baseline and change from baseline in DermaTOP parameters Ra, Rz, Sa and Stm will be 
summarised (N, mean, standard deviation, median, minimum and maximum) by 
treatment arm (test product, Olay ProX Wrinkle Smoothing Cream, no treatment) for 
each study visit (weeks 2 and 4). For each parameter, test product versus no treatment 
and positive control versus no treatment will be compared for the change from 
baseline at 2 weeks, and 4 weeks (primary endpoint), using analysis of covariance 
(ANCOVA) with subject (random effect), treatment, and side of face as main effects 
and baseline value as covariate. This approach allows for the  inclusion of data from 
all subjects treated with a given treatment arm (test product, positive control or no 
treatment) regardless of the treatment group (test product/no treatment, test 
product/positive control, positive control/no treatment) to which they were 
randomised to derive estimates of treatment effect. If the assumption of normality is 
rejected, an appropriate transformation to the data will be performed to facilitate the 
above method of analysis. In the absence of an appropriate data transformation, non-
parametric analyses will be performed. Least square means from the ANCOVA 
model for the change from baseline will be presented for each treatment arm and 
pairwise treatment comparison, together with the 95% confidence intervals.  
The same presentation and analysis methods, as outlined above, will be performed 
using change from baseline for other parameters; clinical Fitzpatrick wrinkle score 
assessment, TEWL values, Corneometer values and Cutometer parameters R5 and 
R7, separately for the Sub-ocular/ Cheek Area. The texture assessment resulting from 
the ranking of photos will inherently be an assessment of change from baseline. As 
such, the data resulting from these rankings will be tabulated by treatment arm as 
proportions with baseline image better and Day 29 image better and analysed using a 
logistic regression.
As this is a POC study, there will be no adjustment to the critical alpha level of 0.05 
to account for inflation due to multiplicity. P-values resulting from inferential testing 
will be considered primarily as summary statistics. 
Adverse events will be summarised by treatment arm.
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1. INTRODUCTION
Wrinkle development, as a direct consequence of skin ageing, has important social 
and psychological impacts which have become exaggerated with longer life 
expectancy and changing social values. The skin ageing process can be separated into 
two simultaneous processes – chronological (or intrinsic) ageing and extrinsic ageing 
(induced by cumulative exposures to environmental factors, especially UV light) 
[Abella ML, 2006]. 
There are many factors at play in skin ageing, one of which involves free radicals, 
which are both generated internally through normal metabolic processes and 
produced as a consequence of external factors, including UV exposure.
As the protective anti-oxidant mechanisms decline in age, free radicals accumulate in 
the body and alter both the proteins and the DNA in the skin. The chronic 
inflammatory state compromises skin health and accelerates the aging process; for 
example, proteolytic enzymes are produced, resulting in collagen degradation 
[Bennett MF, 2007].
Other changes resulting from the intrinsic and extrinsic factors that impact the 
appearance of fine lines, wrinkles and texture include the following, thickness of the 
epidermis, cellular turnover rate of both the epidermis and the SC declines, and 
epidermal differentiation is altered [Gilchrest BA, 1983, Wulf HC, 2004]. The dermis 
becomes thinner as major structural molecules including collagen, elastin and 
glycosaminoglycan decrease in amount [West MD 1989, Millis AJ 1992, and Wick M 
1994]. Metalloproteinase activity also decreases in photodamaged skin and the 
structure of these molecules becomes disorganised and crosslinked [Varani J 2000, 
Francis C 1984, Lavker RM 1987, Uitto J 1989, Kligman LH 1986].
Convolution of dermal-epidermal junction (Rete ridges) flattens with age, resulting in 
a loss of mechanical strength. This also leads to decreased microcirculation to the 
upper dermis and, thus, decreased nourishment to the epidermis [Quan T 2004, 
Lohwasser C 2006].
Age-related changes in inter- and intra-cellular signalling lead to decreases in 
collagen synthesis. Changes in hyaluronic acid content within the skin varies with 
age. Hyaluronic acid is a natural moisturiser within the skin binding up to 1000 times 
its weight in water. Age-related declines result in compromised moisturisation and 
firmness [Ghersetich I, 1994, Schachtschabel DO 1978]. Decrease in intracellular 
energy sources including Adenosine Tri-Phosphate (ATP) and Nicotinamide adenine 
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dinucleotide phosphate (NADH) lead to an inability of skin cells to sustain youthful 
skin biochemistry, thereby reducing the skin’s ability to maintain and restore youthful 
skin structure [Bisset DL, 2005].
Collectively, the changes, work together to compromise skin’s elasticity, firmness 
and structure, which contributes to areas of collapse and irregularity and ultimately 
manifests as fine lines, wrinkles and texture problems.
A key wrinkle-prone region of concern is the periorbital area; this is where the first 
signs of ageing usually appear [Kaczvinsky JR, 2009]. The periorbital area includes 
not only the crow’s feet region but also the intraorbital/ infraorbital region [Bissett
DL, 2005]. 
Skin Texture can be found on many areas of the face, which include bumpy texture 
and enlarged pores. Areas of concern are usually found on nose and cheek area. 
It is hypothesised that the test product, which contains humectants to moisturise the 
SC, will help to reduce the appearance of fine lines and wrinkles caused by skin 
dryness. It is also hypothesised that by moisturising the skin and depositing lipids on 
the skin surface, that skin elasticity, barrier function and texture will also be 
improved.
Stratum Corneum (SC) hydration state has profound influence on its biomechanical 
properties, bulk rheology, turgor and, thus, resulting micro- and macro-topography 
where, in simple terms, increased hydration promotes a smoother, less wrinkled SC 
surface. Moreover, when SC hydration is elevated for days or weeks, enhanced 
specific activity of SC desquamatory enzymes contributes to further incremental 
smoothing of SC surface topography [Berardesca E, 2015].
A clinical study, which explored the suggested link between excessive sebum 
secretion and an increased appearance of pores, as well as the effects of a 2% 
niacinamide containing facial moisturiser,  showed that twice-daily use of the 
moisturiser reduced both sebum production and pore parameter compared to baseline 
measures. Overall, self-assessed facial skin appearance improved after using the 
niacinamide-containing moisturiser. Women reported a noticeable decrease in 
oiliness, large/open pores and balanced oily and dry areas of the face [Osborne R, 
2003]. 
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A method for evaluating changes in skin surface profiles is fringe projection by 
DermaTOP, in which phase-shifted fringe patterns are projected onto the skin by a 
computer-controlled digital projection system. These images are used to retrieve the 
3-Dimensional (3D) surface contour of the skin [Callaghan T.M, 2008].
Quality standardised high resolution digital photography can also visibly demonstrate 
facial lines and wrinkles with accuracy.  Coupled with image ranking it is particularly
useful in providing before and after images [Callaghan T.M, 2008].
Of the many undesirable changes in the skin with age, the loss of skin resilience and 
skin sagging as a consequence of both intrinsic and extrinsic ageing is very apparent. 
The cutometer, a method based on skin deformation can measure elasticity by 
distortion of the skin via suction [Wilhelm K.-P, 2008].
The objective of this POC clinical study is to evaluate the cosmetic appearance of fine 
lines and wrinkles benefit delivered by 4 weeks of twice-daily application of the test 
product on fine lines and wrinkles, texture, barrier function, hydration and elasticity 
to subjects presenting visible signs of ageing. 
2. OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary
Evaluation of wrinkle dimensions 
(change from baseline) of test product 
compared to no treatment on the 
Periocular / Crow’s Feet Area.  
DermaTOP parameter Ra at 4 weeks.
Secondary
Evaluation of wrinkle dimensions 
(change from baseline) of test product 
and positive control compared to no 
treatment in the Periocular / Crow’s Feet 
Area.  
DermaTOP parameter Ra at 2 weeks and 
4 weeks (positive control only)
DermaTOP parameters Rz, Sa and Stm at 2 
and 4 weeks
Clinical Fitzpatrick Wrinkle Score at 2 
and 4 weeks
Evaluation of skin moisturisation (change 
from baseline) of test product and 
positive control compared to no treatment 
Instrumental Corneometer values at 2 and 
4 weeks
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on the Sub-ocular/ Cheek Area. 
Evaluation of texture (change from 
baseline) of test product and positive 
control compared to no treatment on the 
full face. 
Texture ranking at 4 weeks
Evaluation of skin elasticity (change 
from baseline) of test product and 
positive control compared to no treatment 
on the Sub-ocular/ Cheek Area. 
Instrumental Cutometer parameters R5 
and R7 at 2 and 4 weeks
Evaluation of skin barrier (change from 
baseline) of test product and positive 
control compared to no treatment on the 
Sub-ocular/ Cheek Area. 
Instrumental Trans-Epidermal Water 
Loss (TEWL) values at 2 and 4 weeks
To evaluate the general safety of the 
study products
Assessment of frequency and severity of 
Adverse Events (AEs)
3. STUDY PLAN
3.1. Study Design
Overall Design
This is a single-site, 3-arm, randomised, evaluator-blind, positive controlled (Olay 
ProX Wrinkle Smoothing Cream) and no-treatment controlled split-face POC study to 
evaluate the cosmetic appearance of fine lines and wrinkles provided by 4 weeks of 
twice-daily application of the test product in healthy subjects presenting visible signs 
of ageing.
Subjects will give their written consent prior to any study procedures taking place.
At the Screening Visit, only healthy female subjects aged 30 to 65 (inclusive), with a 
Fitzpatrick phototype I-IV, a visual Clinical Fitzpatrick Wrinkle Score of 3-6 in the 
Periocular / Crow’s Feet Area with an equal rating on both sides of the face 
(Appendix 3), with self-reported sensitive skin will be considered eligible to continue 
in the study. 
Eligible subjects will undergo a 3 day washout period, where they will be asked to 
avoid using any other skin care products (moisturisers, lotions, creams, soaps, 
cleansing products, foundations etc.) on their face from the screening visit until Visit 
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2 (Day 1) other than the cleanser provided (SimpleTM Kind to Skin Moisturising 
Facial Wash™). Subjects will be asked to use the study cleanser mornings and 
evenings in the washout period and during the study. On clinic days, subjects will use 
the cleanser in the evenings only and wash their face in the morning with tap water.
Subjects successfully completing the washout phase and who continue to be eligible, 
will have their wrinkles assessed using the Clinical Fitzpatrick Wrinkle Score.  
Subjects who meet all the inclusion/exclusion criteria will be randomised to one of 
three treatment groups: test product/positive control, test product/no treatment or 
positive control/no treatment at the baseline visit. Product application within 
treatment group will be further randomised to either the right or left side of the face.
Diary Cards will be provided and reviewed at each site visit by the Investigator or 
designee to confirm and encourage subject compliance.  Subjects will be required to 
complete the diary card every day to record application of test and study cleanser 
products.
Subjects will be instructed to apply each test product to the assigned side of the face, 
as applicable, (approximately 2 mg / cm2) twice-daily (morning and evening, 
approximately 8-12 hours apart), for 4 weeks (28 days).  Subjects will return to the 
site on Day 15 (Visit 3) and 29 (Visit 4) without applying the test product at home 
that morning.
After randomisation, subjects who consent will have high resolution images taken on 
the left and right side of their face. Instrumental measures will follow in the following 
order: DermaTOP (Periocular / Crow’s Feet Area), TEWL (Sub-ocular/ Cheek Area); 
Corneometer (Sub-ocular/ Cheek Area); Cutometer (Sub-ocular/ Cheek Area). The 
same schedule of events (except randomisation and high resolution photos) will be 
repeated for Day 15 (Visit 3). Day 29 (Visit 4) will be a repeat of Visit 2 (Day 1) 
(except randomisation).
Prior to all instrumental measurements and clinical assessments, subjects will be 
acclimatised in a controlled environment (temperature 20-22ºC, relative humidity
between 40-60%) for a period of at least 30 minutes [EEMCO, 1997].
On Day 1 (Visit 2) and Day 15 (Visit 3) on-site application of product will be 
supervised by the study site staff and will be performed only after the clinical and 
                                               
™Simple Kind to Skin Moisturising Facial Wash is a trademark of Unilever.
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instrumental measurements are completed.
After the study has completed, all of the high resolution images will be evaluated by 
blinded lay persons to rank the appearance of texture.  
Visit 1 – Screening / Washout Visit
The following assessments will be conducted in the order written:
1. Informed consent
2. Demographics
3. Medical History
4. Current / Concomitant medication
5. Fitzpatrick Skin Type assessment (Appendix 2)
6. Clinical Fitzpatrick Wrinkle Score (Appendix 3)
7. Inclusion / Exclusion Criteria
8. Subject Eligibility
9. Study Cleanser and Diary Dispensing
Visit 2 – Baseline Visit
The following assessments will be conducted in the order written:
1. Current / Concomitant medication
2. Adverse Events 
3. Diary Review (Compliance)
4. Continued Eligibility
5. Clinical Fitzpatrick Wrinkle Score (Appendix 3)
6. Inclusion / Exclusion Criteria
7. Subject Eligibility
8. Randomisation
9. High Resolution Photos for Texture Assessment (Appendix 4)
10. DermaTOP Assessment
11. TEWL Assessment
12. Corneometer Assessment
13. Cutometer Assessment
14. Test Product(s) Dispensing
15. Supervised Test Product Application
Visit 3- Day 15 (Week 2)
The following assessments will be conducted in the order written:
1. Current / Concomitant medication
2. Adverse Events 
3. Diary Review (Compliance)
4. Continued Eligibility
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5. Clinical Fitzpatrick Wrinkle Score (Appendix 3)
6. DermaTOP Assessment
7. TEWL Assessment
8. Corneometer Assessment
9. Cutometer Assessment
10. Supervised Test Product Application
Visit 4 – Day 29 (Week 4)
The following assessments will be conducted in the order written:
1. Current / Concomitant medication
2. Adverse Events
3. Diary Review (Compliance)
4. Continued Eligibility
5. Clinical Fitzpatrick Wrinkle Score (Appendix 3)
6. High Resolution Photos for Texture Assessment (Appendix 4)
7. DermaTOP Assessment
8. TEWL Assessment
9. Corneometer Assessment
10. Cutometer Assessment
11. Test Product, Study Cleanser and Diary Return
12. Subject Discharge from Study
3.2. Subject Restrictions
Lifestyle/ Dietary
During the entire study (screening – LSLV):
Subjects are not permitted to join any other cosmetic or therapeutic study.
Subjects must not be planning on taking holiday outside of their home country.
Subjects must avoid water sports including sailing, diving, swimming and winter 
sports including skiing and snowboarding.
Subjects must not smoke or start smoking during the study (including use of e-
cigarettes).
Subjects will not be permitted to use any other skin care products (moisturisers, 
moisturising foundations, lotions, creams, sunscreens, soaps, cleansing, exfoliation 
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products, etc.) or begin the use of any new facial products on their face following the 
screening visit and for the duration of the study, other than the study cleanser 
SimpleTM Kind to Skin Moisturising Facial Wash and the assigned test products 
provided.
Subjects will be asked to use the study cleanser mornings and evenings in the 
washout period and during the study. 
On the day of site visit:
Subjects will be required to attend the screening and baseline visit wearing no make-
up. Mascara and lipstick are permitted to be worn.
Subjects must cleanse their face with only tap water on the morning of the visit at 
least 2 hours prior to the visit. 
Subjects will use the cleanser in the evenings only and wash their face in the morning 
with tap water.
Subjects must not apply any other cosmetic or medicated treatment on the face, 
including the test products provided (Subjects will be instructed to apply the test 
product at least 12 hours before the study appointment).
Subjects must bring their test products with them to the study site.
Subjects must not consume coffee or any product containing caffeine or alcohol 2 
hours priors to the scheduled visit until the end of their visit.
No hard physical exercises (with heavy sweating), sauna, swimming within 24 hrs of 
the site visit.
Medications and Treatments
During the entire study (screening – LSLV):
Subjects must not use any study prohibited medication as specified in the exclusion 
criteria.
Subjects must not use any other cosmetic or medicated treatment on the face, other 
than the test products provided. 
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Female subjects of child-bearing potential must use effective contraception
Subjects must not change any hormonal treatment or contraception that they may be 
receiving and must have used the same contraception for 3 months prior to screening.
Subjects must not undergo any aesthetic, cosmetic or dermatological treatment in the 
treatment area (face or eyes) including facial hair removal, except for plucked eye 
brows.
Subjects must avoid photodynamic therapy, laser therapy, microdermabrasion for 
acne.
Subjects must avoid exposure to artificial ultraviolet (UV) light or cosmetic 
procedures (includes tanning beds, Intense Pulsed Light (IPL), etc.) for the duration 
of the study.
3.3. Type and Planned Number of Subjects
Healthy female volunteers, aged 30 to 65 (inclusive) with a Fitzpatrick phototype 
score of I-IV, presenting visible signs of ageing with a visual Clinical Fitzpatrick 
Wrinkle Score of Score 3-6 in the Periocular / Crow’s Feet Area with an equal rating
on both sides of the face (Appendix 3), with self-reported sensitive skin will be 
considered eligible to continue in the study. 
Approximately 90 healthy subjects will be screened to randomise at least 72 subjects 
to ensure 66 subjects complete the entire study. This will ensure approximately 44 
subjects per treatment arm (test product, positive control, no treatment) or 22 per 
treatment group (test product/no treatment, test product/positive control, positive 
control/no treatment).
The sample size is based on clinical considerations.  With 40 subjects, a difference 
between test product and no treatment in the change from baseline in Ra of at least 
46% of the magnitude of the within-subject standard deviation of the difference 
would be detectable at two-sided alpha=0.05 with approximately 80% power.

3.4. Study Design and Dose Justification
This is a single-site, 3-arm, randomised, evaluator-blind, positive controlled (Olay 
ProX Wrinkle Smoothing Cream) and no-treatment controlled split-face POC study to 
evaluate the cosmetic appearance of fine lines and wrinkles provided by 4 weeks of 
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twice-daily application of the test product in healthy subjects presenting visible signs 
of ageing.
A split-face design has been selected to enable each subject to act as their own 
control. Subjects will be recruited to ensure they present the same wrinkle grades on 
both sides of their face at screening and baseline and a left-right treatment 
randomisation will be employed to ensure a consistent baseline between groups.
A positive control has been included in the design to help validate the trial results. 
Olay ProX Wrinkle Smoothing Cream has been selected as the positive control in 
light of favourable literature data concerning the wrinkle benefits of formulations 
containing similar cosmetic ingredients [Kaczvinsky 2009] and clinically proven 
claims made under the manufacturer.
It is hypothesised that the test product, which contains humectants to moisturise the 
SC, will help to reduce the appearance of fine lines and wrinkles caused by skin 
dryness. It is also hypothesised that by moisturising the skin and depositing lipids on 
the skin surface, that skin elasticity and barrier function will also be improved.
The application quantity of the study product(s) has been selected to reflect typical 
consumer usage of these types of products approximately 2 mg/cm2 [Simion, 2006].
The inclusion criteria number 7, “Skin Type, of Visual Clinical Fitzpatrick Wrinkle 
Score Wrinkle Score 3-6 in the Periocular / Crow’s Feet Area with an equal rating on 
both sides of the face”, (a mild to moderate population for fine lines and wrinkles) has 
been selected based on clinical considerations to ensure a homogeneous population.
A common technique to measure periorbital wrinkles is the DermaTOP system. The 
technique is a non-invasive, fringe projection technique that allows 3-D information 
to be gathered from the skin’s surface and has been evaluated in several studies as a 
sensitive approach with which to precisely demonstrate the effects of topical 
preparations on the topography of human skin [Kaczvinsky 2009].
The Sub-ocular/ Cheek Area will also be evaluated using a variety of other well 
established instrumental measures (TEWL, Corneometer, Cutometer) in order to 
inform future study design. 
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4. SELECTION OF STUDY POPULATION AND 
WITHDRAWAL CRITERIA
Specific information regarding warnings, precautions, contraindications, adverse 
events, and other pertinent information on the GSK investigational product or other 
study treatment that may impact subject eligibility is provided in the Safety 
Statement.
Deviations from inclusion and exclusion criteria are not allowed because they can 
potentially jeopardize the scientific integrity of the study, regulatory acceptability or 
subject safety. Therefore, adherence to the criteria as specified in the protocol is 
essential.
4.1. Inclusion Criteria
A subject will be eligible for inclusion in this study only if all of the following criteria 
apply:
1. CONSENT
Demonstrates understanding of the study procedures, restrictions and willingness to 
participate as evidenced by voluntary written informed consent and has received a 
signed and dated copy of the informed consent form. 
2. AGE
Aged between 30 and 65 years inclusive.
3. GENDER
Subject is female.
4. GENERAL HEALTH
Good general and mental health with, in the opinion of the investigator or medically 
qualified designee, no clinically significant and relevant abnormalities in medical 
history or upon physical examination.
5. CONTRACEPTION
Females of childbearing potential who are, in the opinion of the investigator, 
practising a reliable method of contraception.  Adequate contraception is defined as 
abstinence, oral contraceptive, either combined or progestogen alone OR injectable 
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progestogen OR implants of levonorgestrel OR estrogenic vaginal ring OR 
percutaneous contraceptive patches OR intrauterine device or intrauterine system OR 
double barrier method (condom or occlusive cap [diaphragm or cervical vault caps] 
plus spermicidal agent [foam, gel, film, cream, suppository]) OR male partner 
sterilization prior to the female subject’s entry into the study, and this male is the sole 
partner for that subject.
6. COMPLIANCE
Willingness to actively participate in the study and to attend all scheduled visits.
7. SKIN TYPE
a) Fitzpatrick phototype I-IV (Appendix 2)
b) Visual Clinical Fitzpatrick Wrinkle Score 3- 6 in the eye (crow’s feet) area 
with an equal rating on both sides of the face (Table 1/Appendix 3) at 
screening and baseline.
c) Subjects with self-reported sensitive skin
4.2. Exclusion Criteria
A subject will not be eligible for inclusion in this study if any of the following criteria 
apply:
1. PREGNANCY
Women who are known to be pregnant or who are intending to become pregnant over 
the duration of the study.

2. BREAST-FEEDING
Women who are breast-feeding.
3. CONCURRENT MEDICATION/ MEDICAL HISTORY 
a)
Any history of significant dermatological diseases or conditions or medical 
conditions known to alter skin appearance or physiologic response (e.g. 
diabetes,) which could, in the opinion of the Investigator, preclude topical 
application of the investigational products and/or interfere with the evaluations. 
b)
Change in contraception within the last 3 months.
c)
Presence of open sores, pimples, cysts, irritated skin, hairs or tattoos at the 
application site.
d) Active dermatosis (local or disseminated) that might interfere with the results of 
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the study.
e) Considered immune compromised. 
f)
Currently using any medication which in the opinion of the investigator, may 
affect the evaluation of the study product, or place the subject at undue risk. 
g) Use of the following topical or systemic medications: immunosuppressants, 
antihistamines, non-hormonal anti-inflammatory drugs, and corticosteroids up to 
2 weeks before screening visit.
h) Intention of using any oral or topical steroids 
i)
Regular use of inhaled steroids (occasional use is permitted)
j)
Regular use of topical anti-itch medications (occasional use permitted; the product 
should be applied with an applicator but not to the proposed application areas.
k) Use of any topical drug or medication in the proposed application areas.
l)
Intention of being vaccinated during the study period or has been vaccinated 
within 3 weeks of the screening visit.
m) Currently receiving allergy injections, or received an allergy injection within 7 
days prior to Visit 1, or expects to begin injections during study participation.
n) Blepharitis, conjunctivitis, uveitis.
o) Topical ocular treatment within the last month.
p) Aesthetic, cosmetic or dermatological treatment on the face within the last 3 
months. 
q) Intense sun exposure, UV-treatments or tanning salon visit within the last 2 
weeks.
4. ALLERGY/ INTOLERANCE
Known or suspected intolerance or hypersensitivity to the study materials (or closely 
related compounds) or any of their stated ingredients.
5. CLINICAL STUDY/ EXPERIMENTAL PRODUCT
a) Participation in another clinical study (including cosmetic studies) or receipt 
of an investigational drug within 14 days of the screening visit.
b) Previous participation in this study.
6. SUBSTANCE ABUSE
Recent history (within the last 5 years) of alcohol or other substance abuse.
7. PERSONNEL
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An employee of the sponsor or the study site or members of their immediate family.
8. LIFESTYLE
A smoker
4.3. Screening/ Baseline Failures
Screen failures are defined as subjects who consent to participate in the study but are 
never subsequently randomised, In order to ensure transparent reporting of screen 
failure subjects, a minimal set of screen failure information is required including 
Demography, Screen Failure details, Eligibility Criteria, and any Serious Adverse 
Events. Re-screening of subjects will not be allowed in this study.
4.4. Withdrawal/ Stopping Criteria
A subject may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioural or 
administrative reasons.
If the reason for removal of a subject from the study is an AE or an abnormal 
laboratory test result, the principal specific event or test will be recorded on the 
electronic case report form (CRF).  If a subject is withdrawn from the study because 
of a product limiting AE, thorough efforts should be clearly made to document the 
outcome. Any AEs ongoing at the final visit will be followed up until resolved, the 
condition stabilizes, is otherwise explained, or the subject is lost to follow-up.
The following actions must be taken in relation to a subject who fails to attend the 
clinic for a required study visit:

The site must attempt to contact the subject and re-schedule the missed visit as 
soon as possible where possible. 

The site must counsel the subject on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the subject wishes to 
and/or should continue in the study. 

In cases where the subject is deemed ‘lost to follow up’, the investigator or 
designee must make every effort to regain contact with the subject (where
possible, at least 2 telephone calls). The contact attempt should be 
documented in the subject’s record. 
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
Should the subject continue to be unreachable, only then will he/she be 
considered to have withdrawn from the study with a primary reason of “Lost 
to Follow-up”.
4.5. Subject Replacement
Subjects who withdraw from the study post-randomisation will not be replaced.
4.6. Subject and Study Completion
A completed subject is one who has completed all phases of the study. The end of the 
study is defined as the date of completion of the texture image ranking exercise.
5. PRODUCT INFORMATION
5.1. Study Product
The following study products will be supplied by the Clinical Supplies Department, 
GSKCH:
Test Product 
Reference Product 
Product Name 
Skin Care fine lines and 
wrinkles Chassis
Olay ProX Wrinkle 
Smoothing Cream
Product Formulation 
Code (MFC)
Commercially Available 
(UK)
Application Quantity
approx. 2 mg /cm2
approx. 2 mg /cm2
Route of Application
Dermal Topical
Dermal Topical
Application Instructions
Dispense two pumps of 
product (equating to 
approximately 0.6 mL) 
onto your fingertips and 
apply evenly to the 
randomly assigned side of 
the face, to include, the 
crow’s feet area, cheek, 
forehead and chin twice 
daily, (morning and 
evening), after cleansing. 
Daily applications should 
be approximately 8-12 
Subjects will be instructed 
to apply a pea-sized amount 
of the positive control 
product (equating to 
approximately 0.5g) onto 
your fingertips and apply 
evenly to the randomly 
assigned side of the face, to 
include the crow’s feet area, 
cheek, forehead and chin , 
twice daily (in the morning 
and evening), after 
cleansing. 
Daily applications should be 
approximately 8-12 hours 
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hours apart.
Subjects will be reminded 
that as with all facial skin 
care products, care should 
be taken to avoid getting 
into the eyes. If contact 
does occur, then rinse 
thoroughly with water.
apart.
Subjects will be reminded 
that as with all facial skin 
care products, care should 
be taken to avoid getting 
into the eyes. If contact does 
occur, then rinse thoroughly 
with water.
Other items to be supplied by the Clinical Supplies Department, GSKCH:
Name of Item
Purpose
SimpleTM Kind to Skin Moisturising 
Facial Wash
Study cleanser (Subjects will be asked to 
use the study cleanser mornings and 
evenings in the washout period and 
during the study. On the clinic days, 
subjects will use the cleanser in the 
evenings only and to wash their face in 
the morning with tap water).
5.2. Application Schedule
The usage instructions for the study has been selected to reflect typical consumer 
usage; approximately 2 mg/cm2 (Simion FA, 2006).
A washout period is included to standardise each subject’s skin care regimen prior to 
entering the test phase. During the washout period, subjects will be requested to 
replace their current facial cleanser with the (SimpleTM Kind to Skin Moisturising 
Facial Wash) cleanser. Subjects will be asked to use the cleanser mornings and 
evenings in the washout period and during the study. On the day of the site visit, 
subjects will use the cleanser in the evenings only and to wash their face in the 
morning with tap water.
Subjects will be instructed to apply the study product(s) to clean and dry skin. 
During the test phase, subjects will be instructed to apply two pumps of test product 
(equating to approximately 0.6 mL) and/or a pea-sized amount (equating to 
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approximately 0.5g) of the positive control product to the randomly assigned side of 
the face, to include, cheeks, forehead and chin (approximately 2 mg/cm2) twice daily, 
(morning and evening), after cleansing. 
The first use of the products will be under supervision at the study site at Baseline 
(Day 1). Subsequent use of study products will be applied by the subject at home, as 
instructed by site staff. Subjects will bring their allocated study products with them to 
each post-baseline visit, having applied test and/or reference product at least 12 hrs 
prior to their appointment time.
Subjects will need to be reminded to bring all their study products (test/reference 
product and cleanser) with them to the study site for the subsequent visits. Study 
Product will be returned at Day 29 (Visit 4).
5.3. Application Modification
No modification of product application is permitted in this study.
5.4. Product Compliance
Subjects will be supervised when using the study product at the Baseline (Day 1) visit 
for the first time and at Visit 3 (Day 15) at the site to ensure compliance.  A record of 
the dispensing and administration of the study products will be kept using the 
dispensing and administration log and the eCRF.
Diary Cards will be used to promote compliance and familiarisation during the study
days. Subjects will not be excluded due to over or under use in applications but will 
be reminded to use the study products as per the instructions provided and to 
complete the diary card on a daily basis to encourage compliance.
5.5. Precautions
No special precautions are necessary provided the study is carried out in accordance 
with this protocol.
5.6. Overdose
An overdose is a deliberate or inadvertent administration of a study product at a dose 
higher than specified in the protocol.
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Overdose is not likely to occur in this study.  Limited quantities of the study products
will be supplied, and closely monitored by the site for each subject.
Overdose per se is not an AE.  However, any clinical sequelae of an overdose should 
be reported as an AE (and serious adverse event (SAE), if appropriate).  For 
reporting, follow the AE and SAE reporting instructions.
5.7. Rescue Therapy
No rescue therapy is required in this study.
5.8. Product Assignment
Subjects will be randomised to one of 3 treatment groups in accordance with the 
randomisation schedule generated by the Biostatistics Department, GSKCH, prior to 
the start of the study, using validated internal software: 
Test product/no treatment
Test product/positive control 
Positive control /no treatment 
Randomisation will further include specification of which side of the face to which 
each of the treatments is to be applied. This will ensure that each treatment will be 
applied to each side of the face across all subjects.
5.8.1 Randomisation
A unique screening number will identify each subject screened for study 
participation.  Screening numbers will be assigned in ascending numerical order as 
each subject signs their consent form.  Subjects who meet all inclusion and exclusion 
criteria will be randomised according to the randomisation schedule.  Randomisation 
numbers will be assigned in ascending numerical order as each subject is determined 
to be fully eligible.
The randomisation number will be associated with the treatment group and which 
side of face (either right and/or left) to which study product is to be applied.
The high resolution images will be randomised offline (in advance) using a standard 
block-wise randomisation algorithm on a standard PC (Dell Optiplex 9010). The 
randomisation algorithm is saved in order to reproduce the randomisation, if 
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necessary. The PC is not linked to the rater screens. The randomisations are stored as 
text file which are directly used by the presentation software (proDERM Onlinescore, 
used by the grader). There will be a single randomisation file per grader, so that the 
images will be presented to every grader in a different sequence.
5.8.2 Blinding
The study statistician and other employees of the Sponsor who may influence study 
outcomes will be blinded to the random assignments of product. 
Investigators or designee dispensing the product will be aware of the treatment group 
randomisation including side of face to which treatment will be applied and must not 
divulge information to the other study staff or assessors. 
The assessor performing the measurements will be blinded to the treatment group 
randomisation.
5.8.3 Code Breaks
The blind must only be broken in an emergency where it is essential to know which 
side of the face product(s) have been applied in order to give the appropriate medical 
care.  Wherever possible the Investigator (or designee) must contact the Sponsor prior 
to breaking the blind.  The investigator must document the reason for breaking the 
code and sign and date the appropriate document.
The study blind must be returned to GSKCH at the end of the study.
5.9. Packaging and Labelling
The contents of the label will be in accordance with all applicable regulatory 
requirements and will be the responsibility of the Clinical Supplies Department, 
GSKCH.
The study cleanser (Simple Kind to Skin Moisturising Facial Wash) to be used 
throughout the study will be supplied in commercial packs that will be over-wrapped 
in opaque vinyl to obscure any commercial branding as much as possible. The tubes 
will be supplied with a study label affixed by the Sponsor. Each study label will 
contain, but not be limited to, protocol number and directions for storage.
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The Test product 
 will be supplied in pump tubes with a study label 
affixed by the Sponsor. Each study label will contain, but not be limited to, protocol 
number, treatment group code, application side (Right or Left) and directions for 
storage.
The Reference product (Olay ProX Wrinkle Smoothing Cream) will be supplied in 
commercial packs that will be over-wrapped with opaque vinyl to obscure any 
commercial branding as much as possible. The jars will be supplied with a study label 
affixed by the Sponsor. Each study label will contain, but not be limited to, protocol 
number, treatment group code, application side (Right or Left) and directions for 
storage.
Care should be taken with the supplied products and their labels so that they are 
maintained in good condition. It is important that all labels remain intact and legible 
for the duration of the study. 
5.9.1. Accountability of Product
All products supplied are for use only in this clinical study and should not be used for 
any other purpose.
The investigator or designee will maintain a full record of study product 
accountability. A Product Dispensing Log must be kept current and will contain the 
following information:

The identification of the subject to whom the study product was dispensed.

The date(s) and quantity of the study product dispensed to the subject.

The date(s) and quantity of the study product returned by the subject (if 
applicable).
The inventory must be available for inspection by the study monitor during the study. 
At the end of the study, study product supplies will be verified by the monitor.  Study 
product supplies will then be either collected by the study monitor or returned by the 
investigator or designee to the GSKCH Clinical Supplies Department or designated 
vendor.
5.9.2. Storage of Product
Study product supplies must be stored in compliance with the label requirements in a 
secure place with limited or controlled access.
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6. STUDY ASSESSMENTS AND PROCEDURES
This section lists the procedures and parameters of each planned study assessment.  
The exact timing of each assessment is listed in the Schedule of Events section.
Adherence to the study design requirements, including all assessments and 
procedures are essential and required for study conduct.
6.1. Visit 1 - Screening Visit
6.1.1 Telephone Screening
Prior to the screening visit, telephone screening of interested subjects may be 
conducted. This will be conducted by the site recruitment staff or designee.
Prior to the screening visit potential subjects may be provided with the Subject 
Information Sheet and given the opportunity to ask any questions with the 
Dermatologist prior to signing the Informed Consent form at the screening visit.
6.1.2. Informed Consent
The investigator, or designee, must obtain written (signed and dated by the subject) 
informed consent from each subject participating in this study after adequate 
explanation of the aims, methods, objectives, and potential hazards of the study.
The investigator, or designee, must also explain to the subjects that they are 
completely free to refuse to enter the study, to refuse the high resolution images even 
if they choose to enter the trial, or to withdraw from the trial at any time.  Appropriate 
forms for documenting a written consent will be provided by the investigator or by 
GSKCH.  The investigator, or designee, should sign and date the consent form to 
confirm that the consent process was completed correctly.  The subject, will be 
provided with a copy of their signed and dated consent form and any other written 
information which they should be instructed to retain.
If, during a subject’s participation in the study, any new information becomes 
available that may affect the subject’s willingness to participate in the study, each 
ongoing subject should receive a copy of this new information and be re-consented 
into the study. Subjects should be provided with a copy of the signed and dated 
amended consent form. The date of consent will be recorded on the CRF.
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Subjects may be contacted ahead of the screening visit and provided with the 
Informed Consent to read and consider in advance to give sufficient opportunity to 
discuss with the Investigator prior to consenting.
6.1.3. Demographics
The following demographic parameters will be captured by the Investigator or 
designee and recorded on the CRF: year of birth, gender, race and Fitzpatrick skin 
type. 
6.1.4. Medical History and Concomitant Medication
Medical history will be assessed as related to the inclusion/exclusion criteria by the 
Investigator or medically qualified designee.  Details of any relevant medical or 
surgical history (within the last year), including allergies or drug sensitivity, will be 
recorded on the CRF.  Any concomitant therapy taken in the 30 days prior to the 
Screening Visit and throughout the study will also be recorded.
6.1.5. Clinical Fitzpatrick Wrinkle Assessment in Periocular / Crow’s Feet 
Area 
Subjects will be acclimatised in a controlled environment (temperature 20-22ºC,
relative humidity between 40-60%) for a period of at least 30 minutes before the
clinical assessments are performed [EEMCO, 1997].
A blinded, trained and qualified examiner will perform Clinical Fitzpatrick Wrinkle 
Score assessments by visually grading the crow’s feet area under standard conditions 
of illumination. Non-polarised lighting (LED panels with a colour temperature of 
6000 Kelvin and a colour rendering index of 96, Eva Lux Bench, by Orion Techno 
Lab), which causes a shine (by turning on only the upper light source) that enhances 
topographic features (fine lines and wrinkles). Subjects will have their hair and 
clothing covered with black drapes. Conditions (lighting, distance and head position) 
will be fixed by using a chin rest fixed on the Eva Lux Bench at all time points for the 
same subject. These assessments will be performed at Visit 1 (day -3), Visit 2 (day 1), 
Visit 3 (Day 15) and Visit 4 (Day 29).
Refer to Table 1 below for the 9-point visual rating scale (VRS) used in this 
assessment [Elsner P, 2011]. Refer to Wrinkle Score according to Fitzpatrick at the 
end of Appendix 3 for a visual differentiation of each score/class.
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Table 1: Fitzpatrick Wrinkle Score Periocular / Crow’s Feet Area 
Fitzpatrick Wrinkle Score
 
 
 
 
 
 
 
 
 
6.2. Visit 2 - Baseline Visit Day 1
Subjects will be randomised to a treatment group and side of face (Left or Right) to 
which each product should be applied after all the assessments below are performed 
(baseline). First use of the product(s) will be supervised by site staff as per directions 
provided, however this will be after all clinical and instrumental measures have been 
taken on the day.
Subjects will be acclimatised in a controlled environment (temperature 20-22ºC,
relative humidity between 40-60%) for a period of at least 30 minutes before the
instrumental and clinical assessments are performed (at each time point) [EEMCO, 
1997].
6.2.1 USR- CliP High Resolution Images
 
 
 
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Informed consent will be sought from the subjects for the use of photographs taken of 
their face during this study and for the purpose of Ad-hoc analysis by the sponsor 
company.
After the study has completed, all of the high resolution images will be assessed by 
24 lay raters at one time to evaluate texture (pores, smoothness and unevenness). 
The lay raters will come to the study site on image assessment days and will be 
informed about the assessment and will give their written informed consent to 
participate, which includes the following inclusion/exclusion criteria (Inclusion: 18 to 
70 years; knowledge how to use a computer, Exclusion: problems with the eyes; 
change of lenses or glasses within the last 7 days before the start of the study; 
migraine or headache on the assessment day).
 
 
The 24 lay raters will be recruited from ProDERMs database.  Once the ‘rater’ 
Informed Consent is signed, proDERM are to explain the imaging assessment process 
(2 images on the same screen that have to ranked), and how the scale works and how 
the subjects are to use the software. 
 
 
 
 
 
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. 
 
 
 
 
  
 
 
 
 
6.2.2. DermaTOP Technique
 
 
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Please see below for definitions and formulas for the assessed DermaTOP 
parameters:
 
 
 
 
 
 
 
 
 
 
 
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6.2.3 Transepidermal Water Loss (TEWL)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6.2.4. Corneometry Assessment
 
 
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.
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6.2.5.Cutometer Assessment
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6.3. Visit 3 (Day 15)
Subjects will return to the study site without having applied product that morning.
                                               
® Cutometer is a registered trademark of Courage + Khazaka electronic GmbH 
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Subjects will repeat assessments as per Baseline, Visit 2 (Day 1), except for
randomisation, product dispensing and USR CliP High Resolution Images.
Following clinical and instrumental assessments, subjects will apply product under 
site supervision.
6.4. Visit 4 (Day 29)
Subjects will return to the study site without having applied product that morning, no 
product will be applied on this day.
Subjects will repeat assessments as per Baseline, Visit 2 (Day 1) except for 
randomisation and product dispensing as this will occur on Baseline, Visit 2, and 
(Day 1) only.
Subjects will return the test product(s), cleanser and diary card. Subjects will be 
evaluated to determine if they completed all study procedures or if they were 
discontinued from the study early.  If the subject discontinued at any point during the 
study, the primary reason for withdrawal should be recorded on the Study Conclusion 
page of the CRF by selecting one of the options below.
1.
Subject did not meet study criteria
2.
Adverse Event
3.
Lost to Follow Up
4.
Protocol Violation
5.
Withdrawal of Consent
6.
Other
7. SAFETY ASSESSMENTS
7.1. Definitions of an Adverse Event and Serious Adverse Event 
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7.1.1. Adverse Events
The investigator or site staff will be responsible for detecting, documenting and 
reporting events that meet the definition of an AE or SAE.
Adverse Event Definition:

An AE is any untoward medical occurrence in a patient or clinical 
investigation subject, temporally associated with the use of an investigational 
or washout product, whether or not considered related to the investigational or 
washout product.

NOTE: An AE can therefore be any unfavourable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease (new or 
exacerbated) temporally associated with the use of an investigational or 
washout product.
Events meeting AE definition include:

Any abnormal laboratory test results (if applicable) or other safety 
assessments, including those that worsen from baseline, and felt to be 
clinically significant in the medical and scientific judgment of the 
investigator.

Exacerbation of a chronic or intermittent pre-existing condition including 
either an increase in frequency and/or intensity of the condition.

New condition(s) detected or diagnosed after study product administration 
even though it may have been present prior to the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either 
study product or a concomitant medication (overdose per se will not be 
reported as an AE/SAE).
Events NOT meeting definition of an AE include:

Any clinically significant abnormal laboratory findings (if applicable) or other 
abnormal safety assessments which are associated with the underlying disease, 
unless judged by the investigator to be more severe than expected for the 
subject’s condition. 

The disease/disorder/ condition being studied or expected progression, signs, 
or symptoms of the disease/disorder being studied, unless more severe than 
expected for the subject’s condition.. 

Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition 
that leads to the procedure is an AE.

Situations where an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen.
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7.1.2. Serious Adverse Events
Serious Adverse Event is defined as any untoward medical occurrence that, at 
any dose:
A. Results in death
B. Is life-threatening
NOTE: The term 'life-threatening' in the definition of 'serious' refers to an 
event in which the subject was at risk of death at the time of the event.  It does 
not refer to an event, which hypothetically might have caused death, if it were 
more severe.
C. Requires hospitalization or prolongation of existing hospitalization
NOTE: In general, hospitalization signifies that the subject has been detained 
(usually involving at least an overnight stay) at the hospital or emergency 
ward for observation and/or treatment that would not have been appropriate in 
the physician’s office or out-patient setting.  Complications that occur during 
hospitalization are AEs.  If a complication prolongs hospitalization or fulfils
any other serious criteria, the event is serious.  When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered 
serious.
Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE.
D. Results in disability/incapacity
NOTE: The term disability means a substantial disruption of a person’s ability 
to conduct normal life functions.
This definition is not intended to include experiences of relatively minor 
medical significance such as uncomplicated headache, nausea, vomiting, 
diarrhoea, influenza, and accidental trauma (e.g. sprained ankle) which may 
interfere or prevent everyday life functions but do not constitute a substantial 
disruption.
E. Is a congenital anomaly/birth defect
F. Other Situations

Medical or scientific judgment should be exercised in deciding 
whether reporting is appropriate in other situations, such as important 
medical events that may not be immediately life-threatening or result 
in death or hospitalization but may jeopardize the subject or may 
require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These should also be 
considered serious.

Examples of such events are invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, 
blood dyscrasias or convulsions that do not result in hospitalization or 
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development of drug dependency or drug abuse or reports of 
spontaneous abortion.
7.2. Recording Adverse Events and Serious Adverse Events
Recording of adverse events and serious adverse events:

The investigator or site staff will be responsible for detecting, documenting 
and reporting events that meet the definition of an AE or SAE. 

The investigator or site staff will then record all relevant information 
regarding an AE/SAE in the CRF.

There may be instances when copies of medical records for certain cases are 
requested by GSK.  In this instance, all subject identifiers, with the exception 
of the subject number, will be blinded on the copies of the medical records 
prior to submission to GSK.

The investigator will attempt to establish a diagnosis of the event based on 
signs, symptoms, and/or other clinical information.  In such cases, the 
diagnosis will be documented as the AE/SAE and not the individual 
signs/symptoms. Clinical AEs will be described by diagnosis and not by 
symptoms when possible (e.g., upper respiratory tract infection, seasonal 
allergy, etc. instead of runny nose).

AEs will be collected from the start of the washout product and until 5 days 
following last administration of the study product.

SAEs will be collected over the same time period as stated above for AEs.  
However, any SAEs assessed as related to study participation (e.g., 
investigational product, protocol mandated procedures, invasive tests, or 
change in existing therapy) or related to a GSK concomitant medication will 
be recorded from the time a subject consents to participate in the study up to 
and including any follow-up contact.  

Medical conditions reported prior to the time period for reporting AEs/SAEs 
should be recorded as part of the subject’s medical history.
7.3. Evaluating Adverse Events and Serious Adverse Events
Assessment of Intensity:
The investigator or designee will make an assessment of intensity for each AE and 
SAE reported during the study and will assign it to one of the following categories:

Mild:  An event that is easily tolerated by the subject, causing minimal 
discomfort and not interfering with everyday activities.

Moderate:  An event that is sufficiently discomforting to interfere with normal 
everyday activities

Severe:  An event that prevents normal everyday activities. - an AE that is 
assessed as severe will not be confused with an SAE. Severity is a category 
utilized for rating the intensity of an event; and both AEs and SAEs can be 
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assessed as severe.
Note: An event is defined as ‘serious’ when it meets at least one of the pre-defined 
outcomes as described in the definition of an SAE.
Assessment of Causality:

The investigator is obligated to assess the relationship between study product 
and the occurrence of each AE/SAE.

A "reasonable possibility" is meant to convey that there are facts/evidence or 
arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as natural history of the underlying diseases, 
concomitant therapy, other risk factors, and the temporal relationship of the 
event to the study product will be considered and investigated.

The investigator will also consult the Investigator Brochure (IB) and/or 
Product Information, for marketed products, in the determination of his/her 
assessment.

For each AE/SAE the investigator must document in the medical notes 
(source document) or CRF that he/she has reviewed the AE/SAE and has 
provided an assessment of causality.

There may be situations when an SAE has occurred and the investigator has 
minimal information to include in the initial report to GSK.  However, it is 
very important that the investigator always make an assessment of 
causality for every event prior to the initial transmission of the SAE data 
to GSK.

The investigator may change his/her opinion of causality in light of follow-up 
information, amending the SAE data collection tool accordingly.

The causality assessment is one of the criteria used when determining 
regulatory reporting requirements.
7.4. Reporting Adverse Events and Serious Adverse Events
AE Reporting to GSKCH:

AEs will be recorded in the AE section of the CRF. 

Medical conditions recorded by the subject on a diary card or similar 
document that meet the definition of an AE must also be recorded in the AE 
section of the CRF, if not previously well-characterized by the investigator in 
the subject’s medical history. 

AEs elicited by the investigator in a standard manner at the study visits should 
also be recorded in the AE section of the CRF.  The investigator or designee 
must ask the subject the following question during each visit including any 
follow-up visits:  “Have you felt unwell, experienced any symptoms or taken 
any medication (since your last visit) (today) (since your last dose) (since the 
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last session)?”

The medically qualified investigator should review adverse events in a timely 
manner; this review should be documented in writing in the source document 
or in the CRF. 

After the study is completed at a given site, and the site has received their 
study data on Compact Discs (CDs), the electronic data collection tool will be 
removed from the internet to prevent the entry of new data or changes to 
existing data.
SAE Reporting to GSKCH:
A paper copy of the SAE form provided in the investigator study master file should 
be completed as fully as possible. 
It is essential to enter the following information: 

Protocol and subject identifiers

Subject’s demography

Description of events, with diagnosis if available

Investigator opinion of relationship to study product (see section 7.3)

Criterion for seriousness.
The following are desirable and are of particular relevance for investigator and 
GSKCH 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 on study product

Outcome if known
The SAE form, completed as fully as possible, and SAE fax cover sheet must be 
faxed or e-mailed to the appropriate GSKCH Study Manager as soon as possible, but 
not later than 24 hours after study site personnel learn of the event. The GSKCH 
Study Manager should be notified of the situation by telephone or email.
Fax Serious Adverse Events to:
UK: 
The GSKCH Study Manager will be responsible for forwarding the SAE form to the 
Case Management Group, Global Clinical Safety and Pharmacovigilance, the 
Medical Director responsible for the study and other GSKCH personnel as 
appropriate via email.
The initial report will be followed up with more information as relevant, or as 
requested by the GSKCH study manager.
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PPD

7.5. Follow-up of Adverse Events and Serious Adverse Events
Follow-up of AEs and SAEs:

After the initial report, the investigator is required to proactively follow up 
with each subject and provide further information on the subject’s condition.

All AEs/SAEs will be followed until resolution, until the condition stabilizes, 
until the event is otherwise explained, or until the subject is lost to follow-up.  

The investigator is obligated to perform or arrange for the conduct of 
supplemental measurements and/or evaluations as may be indicated or as 
requested by GSK to elucidate as fully as possible the nature and/or causality 
of the AE or SAE.

Investigators are not obliged to actively seek AEs or SAEs in former subjects.  
However, if the investigator learns of any SAE, including the death, at any 
time after a subject has been discharged from the study, and considers the 
event reasonably related to the investigational product or study participation, 
the investigator will promptly notify GSKCH.

The investigator will submit any updated SAE data to GSK within the 
designated reporting time frames.
Regulatory and ethics reporting requirements for SAEs:

The investigator will promptly report all SAEs to GSKCH within the 
designated reporting timeframes (within 24 hours of learning of the event).  
GSKCH has a legal responsibility to notify, as appropriate, the local 
regulatory authority and other regulatory authorities about the safety of a 
product under clinical investigation.  Prompt notification of SAEs by the 
investigator to GSKCH is essential so that legal obligations and ethical 
responsibilities towards the safety of subjects are met.

GSKCH will comply with country specific regulatory requirements relating to 
safety reporting to the regulatory authority, IEC and investigators.

Investigator safety reports are prepared according to GSKCH policy and are 
forwarded to investigators as necessary.  An investigator safety report is 
prepared for a SAE(s) that is both attributable to investigational product and 
unexpected.  The purpose of the report is to fulfil specific regulatory and GCP 
requirements, regarding the product under investigation.

An investigator who receives an investigator safety report describing a SAE(s) 
or other specific safety information (e.g., summary of listing of SAEs) from 
GSKCH will file it with the Investigator Brochure (or safety statement) and 
will notify the IEC, if appropriate according to local requirements.
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7.6. Collection of Pregnancy Information
7.6.1. Time Period for Collecting of Pregnancy Information
Collection of Pregnancy Information:

Pregnancy information will be collected on all pregnancies reported following 
administration of washout product. Information on pregnancy identified 
during the screening phase and prior to washout product administration does 
not need to be collected.
7.6.2. Action to be Taken if Pregnancy Occurs
Action to be Taken:

The investigator will collect pregnancy information on any subject who 
becomes pregnant while participating in the study after administration of the 
washout product. The investigator will record pregnancy information on the 
appropriate form and submit it to GSKCH within 2 weeks of learning of the 
subject becoming pregnant. The subject will be followed to determine the 
outcome of the pregnancy. Information on the status of the mother and infant / 
neonate (including concomitant medications taken by the mother during the 
pregnancy) will be forwarded to GSKCH. Generally, follow-up will be no 
longer than 6 to 8 weeks following the estimated delivery date. Any 
termination of the pregnancy will be reported.

While pregnancy itself is not considered to be an AE, any pregnancy 
complication or elective termination for medical reasons will be recorded as 
an AE or SAE.

A spontaneous abortion is always considered to be an SAE and will be 
reported as such. An SAE occurring in association with a pregnancy, brought 
to the investigator’s attention after the subject completed the study and 
considered by the investigator as possibly related to the investigational 
product, must be promptly forwarded to GSK.

While the investigator is not obliged to actively seek this information in 
former study participants, he or she may learn of an SAE through spontaneous 
reporting.

If the subject becomes pregnant during the study they should be withdrawn 
from the study and this should be recorded in the appropriate section of the 
CRF.
8. DATA MANAGEMENT
Data Management will be performed by GSKCH. For this study subject data will be 
entered into an electronic case report form, using a GSKCH validated data system. 
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8.1. Source Documents/ Data
The source documents (e.g. hospital records, clinical and office charts, laboratory 
notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing 
records, recorded data from automated instruments, microfiches, photographic 
negatives, microfilm or magnetic media, x-rays, subject files and records kept at the 
pharmacy, at the laboratory and at the medico-technical departments involved in the 
clinical study) which contain the source of data recorded in the CRF should be 
specified in the Source Document Designation Form. In some cases the CRF can be 
used as a source document.
Each subject will be assigned and identified by a unique Screening Number. Any 
reference made to an individual subject within the study must be done using the 
unique Screening Number.
8.2. Electronic Case Report Form
A CRF is a printed, optical, or electronic document designed to record all of the 
protocol required information to be reported to the sponsor on each trial subject.
For each subject who has given informed consent/assent and has been screened, CRF 
must be completed and signed by the Principal Investigator (or authorized designee) 
to certify that the data are complete and correct.  
Management of clinical data will be performed in accordance with applicable 
GSKCH standards and data cleaning procedures to ensure the integrity of the data e.g. 
removing errors and inconsistencies in the data. 
In order to protect the privacy of subjects, no Personally Identifiable Information 
(PII) (including the subject's name or initials or birth date) is to be recorded in the 
CRF or as part of the query text.
Adverse events and concomitant medications terms (if applicable) will be coded 
using MedDRA (Medical Dictionary for Regulatory Activities) and an internal 
validated medication dictionary, GSKDrug.  
Subject data will be entered into GSKCH defined CRFs and transmitted electronically 
to GSKCH in a validated (21 CFR Part 11 compliant) web-based electronic data 
capture system (InFormTM).
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All CRF pages should be completed during a subject assessment when the CRF has 
been designated as the source.  Data that is sourced elsewhere should be entered into 
the CRF in an agreed upon timeframe between the Investigator and Sponsor.  
The CRFs (including queries, query responses and audit trails) will be retained by 
GSKCH. Site data archived compact discs (CD(s)) prepared by a third party will be 
sent to the investigator to maintain as the investigator copy following the 
decommissioning of the study.
8.3. Data Handling
Documentation of all data management activities should allow step-by-step 
retrospective assessment of data 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.
8.3.1. Data Queries
Programmed edit checks will be generated automatically, as the data is being entered 
into the system. Data Management will also run reports and listings on the CRF data, 
in addition to the queries already programmed and generated by the system, to raise 
manual queries as needed for site clarification or correction. The Clinical Dictionary 
Development and Management Group will raise queries as needed on safety data to 
code the terms (Adverse Events and Drugs) are reported appropriately. 
The study monitor at the study site will review the CRFs in accordance with the 
monitoring plan, and any queries will be generated in the EDC System to the 
Investigator or designee, enabling the errors to be addressed in parallel with Data 
Management review. Monitor can also run reports and listings on the CRFs, to raise 
manual queries as needed for site clarification or correction
8.4. External Data
External Data are subject data obtained externally to the CRF. These data are 
generated from laboratory instruments, computers or other sources and then 
transcribed into a file and format agreed upon by GSKCH to identify the subject and 
time point referenced in the CRF and/or protocol. 
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An agreed upon quality control process is performed against the transcribed data to 
the source to ensure the accuracy of the transcription. The transcribed data is 
transmitted in an agreed upon format to GSKCH via secured web portal or CD/DVD 
via mail carrier with tracking capabilities.
Proper reconciliation will be performed between the transcribed data and the clinical 
database to ensure subject and time point referenced in the Clinical Database match 
before Clinical Database Freeze (locking of the database) can occur.
9. STATISTICAL CONSIDERATIONS AND DATA 
ANALYSES
9.1 Sample Size Determination
Approximately 90 healthy subjects will be screened to randomise at least 72 subjects 
to ensure 66 subjects complete the entire study. This will ensure approximately 44 
subjects per treatment arm (test product, positive control, no treatment) or 22 per 
treatment group (test product/no treatment, test product/positive control, positive 
control/no treatment).The sample size is based on clinical considerations.  With 40 
subjects, a difference between test product and untreated in the change from baseline 
in Ra of at least 46% of the magnitude of the within-subject standard deviation of the 
difference would be detectable at two-sided alpha=0.05 with approximately 80% 
power.
9.2. General Considerations
9.2.1. Definition of Analysis Populations
The ‘Intent to treat’ (ITT) population includes all subjects who are randomised into 
the study and have at least one post-baseline clinical assessment available. All 
efficacy analyses will be based on the ITT population.
The Per Protocol (PP) population will consist of the subset of ITT subjects which 
excludes those subjects with significant protocol deviations. Protocol deviations will 
be identified prior to database unblinding and will include, but not be limited to, non-
compliance with the protocol or product application and use of prohibited 
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concomitant medications. Confirmatory analyses of at least the primary efficacy 
endpoint of DermaTOP Ra will be performed on the PP population.
The Safety population will include all subjects with at least one product application to 
either side of the face. All safety analyses will be performed using the Safety 
population.
9.2.2. Exclusion of Data from Analysis
No data will be excluded from any analysis.
9.2.3. Criteria for Evaluation
The primary objective will be to evaluate the change from baseline in wrinkle 
dimensions in the crow’s feet area for the test product compared to no treatment after 
4 weeks of twice daily product application. Given that this is a POC study, the study 
will be considered a success if at least a trend in favour of the test product is 
observed. There will be no adjustment to the critical alpha level of 0.05 to account for 
inflation due to multiplicity. P-values resulting from inferential testing will be 
considered primarily as summary statistics.
9.2.4. Handling of Dropouts and Missing Data
Missing data will not be replaced or imputed. Dropouts will be included in analyses 
up to the point of discontinuation.
9.3. Statistical Methods and Analytical Plan
Additional details of the proposed statistical analysis will be documented in the 
statistical analysis plan (SAP), which will be written following finalisation of the 
protocol and prior to study unblinding / analysis (as appropriate) and performed by 
GSK.
9.3.1. Demographic and Baseline Characteristics
Age and baseline Fitzpatrick wrinkle assessment scores will be summarised 
descriptively using means, medians and standard deviations. Race and Fitzpatrick 
skin type scores will be summarised using frequency counts and percentages.
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9.3.2. Primary Analysis(es)
All efficacy analyses will be performed on the intent to treat (ITT) population.
Baseline and change from baseline in DermaTOP parameters Ra, Rz, Sa and Stm will be 
summarised (N, mean, standard deviation, median, minimum and maximum) by 
treatment arm (test product, Olay ProX Wrinkle Smoothing Cream, no treatment) for 
each study visit (weeks 2 and 4). For each parameter, test product versus no treatment 
and positive control versus no treatment will be compared for the change from 
baseline at 2 weeks, and 4 weeks (primary endpoint), using analysis of covariance 
(ANCOVA) with subject (random effect), treatment, and side of face as main effects 
and baseline value as covariate. This approach allows for the  inclusion of data from 
all subjects treated with a given treatment arm (test product, positive control or no 
treatment) regardless of the treatment group (test product/no treatment, test 
product/positive control, positive control/no treatment) to which they were 
randomised to derive estimates of treatment effect. 
If the assumption of normality is rejected, an appropriate transformation to the data 
will be performed to facilitate the above method of analysis. Least square means from 
the ANCOVA model for the change from baseline will be presented for each 
treatment arm and pairwise treatment comparison, together with the 95% confidence 
intervals. In the absence of an appropriate data transformation, non-parametric 
analysis will be performed.
9.3.3. Secondary Analysis(es)
The same presentation and analysis methods, as outlined above, will be performed 
using change from baseline for other parameters; clinical wrinkle assessment, TEWL 
values, Corneometer values and Cutometer parameters R5 and R7. The texture 
assessment resulting from the ranking of photos will inherently be an assessment of 
change from baseline. As such, the data resulting from these rankings will be 
tabulated by treatment arm as proportions with baseline image better and Day 29 
image better and analysed using a logistic regression.
9.3.4. Safety Analysis(es)
Adverse Events (AE) will be tabulated according to the current version of the 
Medical Dictionary for Regulatory Activities (MedDRA). Frequencies and 
percentages will be presented by treatment arm overall, for each system organ class, 
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and for each preferred term. Summaries of treatment-emergent AE’s, treatment-
related AEs, AEs leading to discontinuation, and serious AEs will be completed.
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10. STUDY GOVERNANCE CONSIDERATIONS
10.1. Posting of Information on Publicly Available Clinical Trials 
Registers
Study information from this protocol will be posted on publicly available clinical trial 
registers before enrolment of subjects begins.
10.2. Regulatory and Ethical Considerations, Including the Informed 
Consent
The study will be conducted in accordance with all applicable regulatory 
requirements, and with GSK policy.
The study will also be conducted in accordance with ICH Good Clinical Practice 
(GCP), all applicable subject privacy requirements, and the guiding principles of the 
current version of the Declaration of Helsinki.  This includes, but is not limited to, the 
following:

Before initiating a trial, the investigator/institution should have written and
dated approval/favourable opinion from the IEC for the trial protocol 
(including amendments), written informed consent form, consent form 
updates, subject recruitment procedures (e.g., advertisements), investigator 
brochure/ safety statement (including any updates) and any other written 
information to be provided to subjects. A letter or certificate of approval will 
be sent by the investigator to the sponsor prior to initiation of the study, and 
also when subsequent amendments to the protocol are made.

Signed informed consent  to be obtained for each subject before participation 
in the study (and for amendments as applicable)

Investigator reporting requirements (e.g. reporting of AEs/SAEs/protocol 
deviations to IEC)

GSK will provide full details of the above procedures, either verbally, in 
writing, or both.
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10.3. Quality Control (Study Monitoring)
In accordance with applicable regulations including GCP, and GSK procedures, GSK 
or designee (i.e. third party vendor) monitors will contact the site prior to the start of 
the study to review with the site staff the protocol, study requirements, and their 
responsibilities to satisfy regulatory, ethical, and GSK requirements.
When reviewing data collection procedures, the discussion will include identification, 
agreement and documentation of data items for which the CRF will serve as the 
source document.
GSK or designee will monitor the study and site activity to verify that the:

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 GSKCH. The investigator (or designee) agrees to allow the monitor direct 
access to all relevant documents and agrees to co-operate with the monitor to ensure 
that any problems detected in the course of these monitoring visits are resolved.
10.4. Quality Assurance
To ensure compliance with GCP and all applicable regulatory requirements, GSK 
may conduct a quality assurance assessment and/or audit of the site records, and the 
regulatory agencies may conduct a regulatory inspection at any time during or after 
completion of the study. 
In the event of an assessment, audit or inspection, the investigator (and institution) 
must agree to grant the advisor(s), auditor(s) and inspector(s) direct access to all 
relevant documents and to allocate their time and the time of their staff to discuss the 
conduct of the study, any findings/relevant issues and to implement any corrective 
and/or preventative actions to address any findings/issues identified.
The sponsor will be available to help investigators prepare for an inspection.
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10.5. Conditions for Terminating the Study
Upon completion or premature discontinuation of the study, the GSKCH monitor will 
conduct site closure activities with the investigator or site staff, as appropriate, in 
accordance with applicable regulations including GCP, and GSKCH Standard 
Operating Procedures.
Both GSKCH and the Investigator reserve the right to temporarily suspend or 
prematurely discontinue this study at any time for reasons including, but not limited 
to, safety or ethical issues or severe non-compliance. For multicenter studies (if 
applicable), this can occur at one or more or at all sites.  
If the trial is prematurely terminated or suspended for any reason, the investigator site 
should promptly inform the trial subjects and should assure appropriate therapy/ 
follow-up for the subjects. Where required by the applicable regulatory requirements, 
GSKCH should inform the regulatory authority (ies). 
In addition: 

If the investigator terminates or suspends a trial without prior agreement of 
GSKCH, the investigator site should promptly inform the sponsor and the 
IEC, and should provide the sponsor and the IEC a detailed written 
explanation of the termination or suspension.

If the GSKCH terminates or suspends a trial, the investigator should promptly 
inform the IEC and provide the IEC a detailed written explanation of the 
termination or suspension. 

If the IEC terminates or suspends its approval/favourable opinion of a trial, the 
investigator should promptly notify the GSKCH and provide GSKCH with a 
detailed written explanation of the termination or suspension.
10.6. Records Retention
Following closure of the study, the investigator must maintain all site study records 
(except for those required by local regulations to be maintained elsewhere), in a safe 
and secure location.  
The records (study/ site master file) must be maintained to allow easy and timely 
retrieval, when needed (e.g., for a GSK audit or regulatory inspection) and must be 
available for review in conjunction with assessment of the facility, supporting 
systems, and relevant site staff.
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Where permitted by local laws/regulations or institutional policy, some or all of these 
records can be maintained in a format other than hard copy (e.g., microfiche, scanned, 
electronic); however, caution needs to be exercised before such action is taken. 
The investigator must ensure that all reproductions are legible and are a true and 
accurate copy of the original and meet accessibility and retrieval standards, including 
re-generating a hard copy, if required.  Furthermore, the investigator must ensure 
there is an acceptable back-up of these reproductions and that an acceptable quality 
control process exists for making these reproductions.
The investigator must assure that the subject’s anonymity will be maintained.  On 
CRFs or other documents submitted to GSKCH, subjects should not be identified by 
their names or initials, but by an identification code. The investigator should keep a 
separate log of subjects’ codes, names and addresses.  Documents not for submission 
to GSKCH, e.g. subjects’ written consent forms, should be maintained by the 
investigator in strict confidence.
GSK will inform the investigator of the time period for retaining these records to 
comply with all applicable regulatory requirements (GSKCH recommends that 
documents be kept for 10 years). The investigator is also required to keep subject 
identification codes on file for at least 15 years after completion or discontinuation of 
the study. The minimum retention time will meet the strictest standard applicable to 
that site for the study, as dictated by any institutional requirements or local laws or 
regulations, GSK standards/procedures, and/or institutional requirements.  
No study document should be destroyed without a prior written agreement between 
GSKCH and the investigator. The investigator must notify GSK of any changes in the 
archival arrangements, including, but not limited to, archival at an off-site facility or 
transfer of ownership of the records in the event the investigator is no longer 
associated with the site.
10.7. Provision of Study Results to Investigators, posting of 
Information on Publicly Available Clinical Trials Registers 
and Publication
Where required by applicable regulatory requirements, an investigator signatory will 
be identified for the approval of the clinical study report. The investigator will be 
provided reasonable access to statistical tables, figures, and relevant reports and will 
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have the opportunity to review the complete study results at a GSK site or other 
mutually-agreeable location.
GSK will also provide the investigator with the full summary of the study results.  
The investigator is encouraged to share the summary results with the study subjects, 
as appropriate.
The procedures and timing for public disclosure of the results summary and for 
development of a manuscript for publication will be in accordance with GSK Policy.
A manuscript will be progressed for publication in the scientific literature if the 
results provide important scientific or medical knowledge.
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11. REFERENCES
Abella ML International Journal of Cosmetic Science, 2006, 28, 447-451
Berardesca E, Ardigo M, Cameli N, Mariano M, Agozzino M, Matts PJ, International 
Journal of Cosmetic Science, 2015, 37, 606–612.
Bennett MF, Robinson MK, Baron ED, Cooper KD. Skin immune systems and 
inflammation: Protector of the skin or promoter of aging? Pending publication. 2007.
Bissett DL, Oblong JE, Berge CA, Dermatologic Surgery, 2005, 31: 860–866.
Bissett DL, Oblong JE, Saud A, Berge CA, Trejo AV, Biedermann KA. Topical 
niacinamide provides skin aging appearance benefits while enhancing barrier 
function. In: Baran R, Maibach HI, eds. Textbook of Cosmetic Dermatology. 
Abingdon, Oxon, UK: Taylor & Francis Group. 2005: 57-62
Biedermann KA. Topical niacinamide provides skin aging appearance benefits while 
enhancing barrier function. In: Baran R, Maibach HI, eds. Textbook of Cosmetic 
Dermatology. Abingdon, Oxon, UK: Taylor & Francis Group. 2005: 57-62.
Callaghan T. M., Wilhelm K.-P, A review of ageing and an examination of clinical 
methods in the assessment of ageing skin. Art 2: Clinical perspectives and clinical 
methods in the evaluation of ageing skin, International Journal of Cosmetic Science, 
2008, 30, 323-332.
DermaTOP V3.0 Calculated Parameters.
EEMCO Guidance for the assessment of stratum corneum moisturisation: electrical 
methods, Berardesca E, The European Group on Efficacy Measurement of Cosmetics 
and other Topical Products. 1997
EEMCO Guidance for the assessment of transepidermal water loss in cosmetic 
sciences, Rogiers, V, Skin Pharmacology and Applied Skin Physiology, 2001 
Elsner P, W.Fluhr J, Gehring W, J. Kerscher  M, Krutmann J, Lademann J, 
Makrantonaki E, Wilhelm KP, C. Zouboulis C, Anti-ageing Data Support Claims-
Consensus Statement  Journal of the German Society of Dermatology 2011,
Francis C, Robert L. Elastin and elastic fibres in normal and pathologic skin. Int J 
Dermatol 1984; 23: 166-179.
Flament F, Bazin R, Laquieze S, Rubert V, Simonpietri E, Piot B, Effects of the sun 
on visible clinical signs of ageing in Caucasian Skin. Clinical, Cosmetic and 
Investigational Dermatology 2013:6 221-232.
Gabiel Koeller (EOTECH) 3D Eotech Training January 12, 2017.
Ghersetich I, Lotti T, Campanile G, Grappone C, Dini G. Hyaluronic acid in 
cutaneous intrinsic aging. Int J Dermatol 1994; 33: 119-122.
Gilchrest BA. In vitro assessment of keratinocyte ageing. J Invest Dermatol 1983; 81: 
184s-189s.
Gilchrest BA. Age associated changes in the skin. J Am Geriatr Soc 1982; 30: 139-
142.
Hatcher RA, Trussell J, Nelson AL, Cates W Jr, Stewart F, Kowal D, editors. 
Contraceptive Technology. 19th edition. New York: Ardent Media, 2007(b): 28.
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ICH Topic 6 Guideline for Good Clinical Practice CPMP/ICH/135/95 17th July 1996.
Varani J, Warner RL, Gharaee-Kermani M, Phan SH, Kang S, Chung JH, et al. 
Vitamin A antagonizes decreased cell growth and elevated collagen-degrading matrix 
metalloproteinases and stimulates collagen accumulation in naturally aged human 
skin. J Invest Dermatol 2000; 114: 480-6.
Kaczvinsky JR, Griffiths CEM, Schnicker MS, Li J, Journal of Cosmetic 
Dermatology, 2009, 8: 228–233.
Kligman LH, Kligman AM. The nature of photoageing: its prevention and repair. 
Photodermatology 1986; 3: 215–227.
Lavker RM, Zheng P, Doug G. Aged skin: a study by light transmission electron and 
scanning electron microscopy. J Invest Dermatol 1987; 88: 44s-51s.
Lohwasser C, Neureiter D, Weigle B, Kirchner T, Schuppan
D. The receptor for advanced glycation end products is highly expressed in the skin 
and upregulated by advanced glycation end products and tumor necrosis factor-alpha. 
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Leigh Mummery 1992. Surface Texture Analysis – The Handbook. Hommelswerke 
GmbH. 
Millis AJ, Hoyle M, McCue HM, Martini H. Differential express of metalloproteinase 
and tissue inhibitor of metalloproteinase genes in aged human fibroblasts. Exp Cell 
Res 1992; 201: 373-379.
Osborne R, Matsubara A, Biedermann K, Hillebrand G, Schnell B, Miyamoto K. 
Improvement in facial surface sebum and pore appearance with niacinamide. Poster 
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collagen-degrading matrix metalloproteinases and stimulates collagen accumulation 
in naturally aged human skin. J Invest Dermatol 2000; 114: 480-6.
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their return. International Journal of Cosmetic Science 2006; 28(3):232
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effect of 2 % niacinamide on facial sebum production 2006
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associated connective tissue alterations in the dermis. J Am Acad Dermatol 1989; 
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activity. Exp. Cell Res 1989; 184: 138–
Wick M, Burger C, Brusselbach S, Lucibello FC, Muller R. A novel member of 
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12. APPENDICES
12.1. Appendix 1 - Abbreviations and Trademarks
Abbreviations
µl
Microlitres
AE
Adverse Event
ANCOVA
Analysis of Covariance
ATP
Adenosine Tri-Phosphate
AUC
Area under Curve
CCD
charge coupled device
CD
Compact Disc
cm2
Centimetre squared
CFR
Code of Federal Regulations
CRF
Case Report Form
DVD
Digital Versatile Disc
EDC
Electronic Data Capture
EEMCO
European Expert Group on Efficacy Measurement of Cosmetics and 
Other Topical Products
DIN EN 
ISO
Deutsches Institut für Normung (German institute for norms) EN= 
European Norm; ISO= International Organization for Standardisation
FOV
Field Of View
GCP
Good Clinical Practice
g
Gram
GSKCH
GlaxoSmithKline Consumer Healthcare
ICH
International Conference on Harmonization of Technical Requirements
for Registration of Pharmaceuticals for Human Use
ICF
Informed Consent Form
IEC
Independent Ethics Committee
ITT
Intention to Treat
LCD
Liquid Crystal Display
LSLV
Last Subject Last Visit
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hr
Hour
mg
milligrams
mL
millilitre
mm
millimetre
MYSQL
Michael Widenius Structured Query Language
NADH
Nicotinamide adenine dinucleotide phosphate
OTC
Over The Counter
PC
Personal Computer
PII
Personally Identifiable Information
PP
Per Protocol
POC
Proof of Concept
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SC
Stratum Corneum
TEWL
Transepidermal Water Loss
VRS
Visual Rating Scale
UV
Ultraviolet
3D
Three Dimensional
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12.2. Appendix 2 - Fitzpatrick Skin Type
 
 
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CCI
CCI

12.3. Appendix 3 – Fitzpatrick Wrinkle Score (Crow’s Feet Area)
Fitzpatrick Wrinkle Score
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12.4. Appendix 4 – Texture Ranking Scale
 
 
 
 
 
             
            
 
             
            
 
 
12.5.Appendix 5 DermaTOPV3 Calculated Parameters
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C
C
I
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SIGNATURE PAGE 
 
  
 
Date 
Signed By
 
Justification 
 
 
 
Date 
Signed By
 
Justification 
 
 
 
Date 
Signed By
 
Justification 
 
 
 
Date 
Signed By
 
Justification 
 
 
 
Date 
Signed By
 
 
Justification 
 
 
 
Date 
Signed By
 
 
Justification 
 
 
 
22-Mar-2017 11:13:21
Approved
24-Mar-2017 07:31:25
Clinical Operations Approval
22-Mar-2017 10:04:09
Biostatistics Approval
Approved
Clinical Protocol 207468.doc
22-Mar-2017 09:34:38
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PPD
PPD
PPD
PPD