Clinical trial NCT02735421
Conditions: Acne Vulgaris Atrophic Acne Scars
Keywords: acne scars
Sponsor: Galderma R&D
Start date: 2016-05-13; Completion date: 2017-11-23
Enrollment: 67 participants; Allocation: RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
This was a multi-centre, randomized, investigator blinded, vehicle controlled trial using intra-individual comparison (right half-face versus left half-face).

Participants with each half-face randomized to one of the two following treatments:

* Adapalene 0.3 percent (%) - benzoyl peroxide (BPO) 2.5% gel (TactuPump® Forte).
* Vehicle gel

The main objective of this trial was to evaluate the effect of Adapalene 0.3% - BPO 2.5% (ABPO Forte) gel versus vehicle gel on the risk of formation of atrophic acne scars in moderate to severe acne participants.

Detailed description:

Arms: arm 1: None arm 2: None arm 3: None arm 4: None
Interventions: intervention 1: ABPO Forte Gel intervention 2: Vehicle gel
Intervention descriptions: intervention 1: Participants applied Adapalene 0.3% - Benzoyl peroxide (BPO) 2.5% gel (ABPO Forte) topically to the affected areas once daily for 24 weeks in Part 1 and for 48 weeks in Part 2. intervention 2: Participants applied placebo matched to ABPO Forte gel topically to the affected areas once daily for 24 weeks in Part 1 and 48 weeks in Part 2.

Protocol documents:
Prot_000.pdf: 
Effect of Adapalene 0.3% - Benzoyl Peroxide 2.5% Gel Versus Vehicle Gel on the Risk of Formation of 
Atrophic Acne Scars in Moderate to Severe Acne Subjects
NCT Number: NCT02735421
Date: 06 July 2016


GALDERMA RESEARCH & DEVELOPMENT 
Protocol N° RD.03.SPR.105061 
Page 1 of 99 
CONFIDENTIAL 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
CLINICAL TRIAL PROTOCOL 
PROTOCOL NUMBER: RD.03.SPR.105061 
CONFIDENTIAL 
This document contains confidential, proprietary information 
All the information provided to the investigator and his/her staff and all data obtained through 
this GALDERMA R&D clinical trial protocol are confidential.  The sponsor reserves all 
proprietary rights. No information may be disclosed to any third party without prior written 
consent from GALDERMA R&D. 


GALDERMA RESEARCH & DEVELOPMENT 
Protocol N° RD.03.SPR.105061 
Page 2 of 99 
CONFIDENTIAL 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
TITLE PAGE 
Title: Effect of Adapalene 0.3% - benzoyl peroxide 2.5% gel versus vehicle gel on the risk of 
formation of atrophic acne scars in moderate to severe acne subjects 
Product Name:  
Project Number: 
Clinical Trial Phase: 
CD0271 0.3%/CD1579 Gel, 
named Tactupump™ Forte in
Canada 
816 
IV 
EUDRACT n°: 2016-002666-31 
IND n°: 067801 
Version Number: 02 FR 
Sponsor Contact details: 
Name 
GALDERMA R&D SNC 
Address 
Les Templiers 
2400, Route des Colles 
06410 Biot - France 
Tel 
+33 (0) 4 93 95 70 68 
Fax 
+33 (0) 4 93 95 71 64 


GALDERMA RESEARCH & DEVELOPMENT 
Protocol N° RD.03.SPR.105061 
Page 3 of 99 
CONFIDENTIAL 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
For any urgent medical questions, including safety reason, please use the contact details 
provided in Section 8.4. 
This clinical trial will be performed in compliance with applicable regulations, Good Clinical 
Practice (GCP) and the ethical principles that have their origin in the Declaration of Helsinki. 
This clinical trial protocol follows guidelines outlined by the International Conference on 
Harmonization (ICH) and the GALDERMA R&D Phase IV department template 


GALDERMA RESEARCH & DEVELOPMENT 
Protocol N° RD.03.SPR.105061 
Page 4 of 99 
CONFIDENTIAL 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
Clinical Trial Administrative Structure 
The following table contains the details of the sponsor’s employees involved in the conduct of the 
trial. 
SPONSOR PERSONNEL 
Name/Title 
Affiliation/Address/Tel./Fax/Email 
Responsibilities 
 
 
 
GALDERMA R&D SNC, 
 
 
  
 
 
 
 
Responsible for clinical 
management and monitoring of 
clinical trial and for overall 
coordination of clinical project 
 
 
 
GALDERMA R&D SNC, 
Same as above 
 
 
 
Responsible for 
administrative follow-up and 
management of Trial Master File 
 
 
GALDERMA R&D SNC, 
Same as above 
 
 
 
Responsible for medical 
management and safety 
surveillance 
 
 
GALDERMA R&D SNC, 
Same as above 
 
 
 
Responsible for the coordination 
of all data management activities 
 
 
GALDERMA R&D SNC, 
Same as above 
 
 
 
Responsible for the management 
of all statistical activities 
 
 
 
GALDERMA R&D SNC, 
Same as above 
 
 
 
Responsible for quality assurance 
and audits  


GALDERMA RESEARCH & DEVELOPMENT 
Protocol N° RD.03.SPR.105061 
Page 5 of 99 
CONFIDENTIAL 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
 
 
GALDERMA R&D SNC, 
Same as above 
 
 
 
Responsible for safety surveillance 
 
 
 
GALDERMA R&D SNC, 
Same as above 
 
 
Responsible for the management 
of all clinical supplies activities for 
France 
 
 
 
Galderma Laboratories, L.P. 
 
 
 
 
Responsible for the management 
of all clinical supplies activities for 
Canada 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 6 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
SIGNATURE PAGE 
INVESTIGATOR'S AGREEMENT 
 
I agree to: 
 
Implement and conduct this clinical trial diligently and in strict compliance with the protocol, Good 
Clinical Practices and all applicable laws and regulations. 
 
Accurately record all required data on each patient’s electronic Case Report Forms (eCRFs) in a 
timely manner on an ongoing basis. 
 
Use the investigational products for this clinical trial only. Maintain a complete and accurate inventory 
during and at the completion of the clinical trial. Maintain records of all investigational product units 
received, dispensed, returned by the subjects, and the number of product units returned to the Sponsor. 
 
Allow authorised representatives of GALDERMA R&D or regulatory authorities to conduct on-site 
visits to review, audit, and copy clinical trial documents. I will personally meet these representatives 
at mutually convenient times to answer any clinical trial-related questions. 
 
Comply strictly with the agreement signed for the carrying out of my services within the scope of this 
protocol, especially with the provisions regarding confidentiality and intellectual property (results and 
publications). 
 
I have read this protocol in its entirety, including the above statement, and I agree to all aspects. 
 
PRINCIPAL INVESTIGATOR 
PRINTED NAME: 
SIGNATURE  
DATE 
 
 
 
 
GALDERMA R&D 
 
SPONSOR REPRESENTATIVE  
PRINTED NAME: 
 
SIGNATURE  
DATE 
 
 
SPONSOR MEDICAL EXPERT 
PRINTED NAME: 
 
SIGNATURE  
DATE 
 
 
 
 
RETURN THE ORIGINAL SIGNED COPY TO GALDERMA R&D AND KEEP A COPY AT YOUR SITE 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 7 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
DISTRIBUTION 
 
Copy of the Protocol 
 
All signatories and, 
 
, GALDERMA R&D 
, GALDERMA R&D 
, GALDERMA R&D 
, GALDERMA R&D 
, GALDERMA R&D 
, Galderma Laboratories, L.P. 
, GALDERMA R&D 
, GALDERMA Canada Inc. 
 GALDERMA France 
, GALDERMA R&D 
, GALDERMA Canada Inc. 
, GALDERMA International – Operations France 
, GALDERMA International 
, GALDERMA International 
 GALDERMA International 
, GALDERMA R&D 
, GALDERMA R&D 
 
Copy of the Synopsis: 
 
 
 GALDERMA R&D 
 
, GALDERMA International 
, GALDERMA International 
 
 GALDERMA Canada Inc. 
, GALDERMA R&D 
 
Original Protocol: 
 
Archives (GALDERMA R&D – Sophia Antipolis) 
 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 8 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
TABLE OF CONTENTS 
SIGNATURE PAGE .............................................................................................................................. 6 
DISTRIBUTION .................................................................................................................................... 7 
TABLE OF CONTENTS ....................................................................................................................... 8 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................................................... 13 
1 
SYNOPSIS .................................................................................................................................... 15 
2 
BACKGROUND AND RATIONALE ........................................................................................ 21 
2.1 
MEDICAL BACKGROUND AND SHORT RATIONALE FOR THE CLINICAL TRIAL .............. 21 
2.2 
INVESTIGATIONAL PRODUCT PROFILE ........................................................................ 23 
2.3 
RISK/BENEFIT ASSESSMENT ...................................................................................... 23 
2.3.1 
Risk-benefit statement related to the clinical trial drugs ............................. 23 
2.3.2 
Risk-benefit statement related to the clinical trial ....................................... 23 
3 
CLINICAL TRIAL OBJECTIVES AND CLINICAL HYPOTHESIS ................................... 24 
3.1 
CLINICAL TRIALS OBJECTIVES .................................................................................... 24 
3.2 
CLINICAL HYPOTHESIS .............................................................................................. 24 
4 
SELECTION AND DISPOSITION OF CLINICAL TRIAL POPULATION ....................... 25 
4.1 
NUMBER OF SUBJECTS ............................................................................................... 25 
4.2 
CLINICAL TRIAL POPULATION CHARACTERISTICS ...................................................... 25 
4.2.1 
Inclusion criteria .......................................................................................... 25 
4.2.2 
Exclusion criteria ......................................................................................... 27 
4.3 
PRIOR AND CONCOMITANT THERAPIES ...................................................................... 28 
4.3.1 
Definition ...................................................................................................... 28 
4.3.2 
Categories..................................................................................................... 29 
4.3.3 
Recording ..................................................................................................... 29 
4.3.4 
Authorized therapies during the clinical trial .............................................. 29 
4.3.5 
Prohibited therapies during the clinical trial ............................................... 30 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 9 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
4.4 
PROCEDURES / REASONS FOR DISCONTINUATION ....................................................... 30 
5 
INVESTIGATIONAL PLAN ...................................................................................................... 32 
5.1 
OVERALL CLINICAL TRIAL DESIGN ............................................................................ 32 
5.2 
DISCUSSION OF CLINICAL TRIAL DESIGN .................................................................... 32 
5.3 
CLINICAL TRIAL DURATION AND TERMINATION ......................................................... 33 
5.4 
CLINICAL TRIAL FLOW CHART ................................................................................... 34 
5.5 
CLINICAL TRIAL VISIT DESCRIPTION AND PROCEDURES ............................................. 36 
5.5.1 
Visit 1 (baseline) (part I) .............................................................................. 36 
5.5.2 
Visit 2 (week 1) (part I) ................................................................................ 37 
5.5.3 
Visit 3 (week 4), 4 (week 8), 6 (week 16) and 7 (week 20)  (part I) ............. 38 
5.5.4 
Visit 5 (week 12) (part I) .............................................................................. 39 
5.5.5 
Visit 8 (week 24) (end of part I, beginning of part II) .................................. 40 
5.5.6 
Visit 9 (week 36) (part II) ............................................................................. 41 
5.5.7 
Visit 10 (week 48) (part II) ........................................................................... 42 
5.5.8 
Early termination visit .................................................................................. 43 
6 
CLINICAL SUPPLIES ................................................................................................................ 44 
6.1 
INVESTIGATIONAL PRODUCT IDENTIFICATION AND USE ............................................. 44 
6.1.1 
Product identity ............................................................................................ 44 
6.1.2 
Method of treatment assignment .................................................................. 45 
6.1.3 
Subject Identification Number (SIN) ............................................................ 46 
6.1.4 
Instructions for use and administration ....................................................... 46 
6.1.5 
Non-investigational products ....................................................................... 47 
6.2 
INVESTIGATIONAL PRODUCT PACKAGING AND LABELING .......................................... 48 
6.3 
INVESTIGATIONAL PRODUCT MANAGEMENT .............................................................. 49 
6.3.1 
Accountability ............................................................................................... 49 
6.3.2 
Dispensing .................................................................................................... 49 
6.3.3 
Investigational product compliance management and record ..................... 50 
6.3.4 
Storage of investigational product ............................................................... 51 
6.3.5 
Return of investigational product ................................................................. 51 
6.4 
DOSE MODIFICATION ................................................................................................. 51 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 10 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
6.5 
BLINDING .................................................................................................................. 52 
6.5.1 
Verification of blinding................................................................................. 52 
6.5.2 
Clinical trial unblinding ............................................................................... 52 
7 
EFFICACY AND SAFETY ASSESSMENT .............................................................................. 54 
7.1 
EFFICACY ASSESSMENTS ........................................................................................... 54 
7.1.1 
Atrophic acne scar count .............................................................................. 54 
7.1.2 
Investigator’s scar global assessment (SGA) ............................................... 55 
7.1.3 
Investigator’s preference in terms of overall scar severity .......................... 55 
7.1.4 
Acne lesion count .......................................................................................... 56 
7.1.5 
Investigator’s global assessment of acne severity (IGA) ............................. 56 
7.1.6 
Investigator’s assessment of the skin roughness .......................................... 57 
7.1.7 
Investigator’s assessment of the skin texture change ................................... 57 
7.1.8 
Quantitative evaluation of skin microrelief (skin replica) ........................... 58 
7.2 
SAFETY ASSESSMENTS ............................................................................................... 58 
7.2.1 
Local tolerability assessment ....................................................................... 58 
7.2.2 
Adverse events .............................................................................................. 60 
7.3 
PATIENT RELATED OUTCOMES ................................................................................... 60 
7.3.1 
Questionnaire on acne scar appearance ...................................................... 60 
7.3.2 
Subject satisfaction questionnaire ................................................................ 60 
7.4 
OTHERS ..................................................................................................................... 61 
7.4.1 
Photographs ................................................................................................. 61 
7.5 
APPROPRIATENESS OF MEASUREMENTS ..................................................................... 61 
8 
ADVERSE EVENTS .................................................................................................................... 62 
8.1 
DEFINITIONS .............................................................................................................. 62 
8.1.1 
Adverse Events (AE) ..................................................................................... 62 
8.1.2 
Serious Adverse Events (SAE) ...................................................................... 63 
8.1.3 
Unexpected adverse drug reaction ............................................................... 64 
8.1.4 
Adverse event reporting period .................................................................... 64 
8.1.5 
Severity ......................................................................................................... 64 
8.1.6 
Relationship to the investigational product .................................................. 65 
8.2 
PROCEDURES FOR REPORTING ADVERSE EVENTS ....................................................... 65 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 11 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
8.3 
PROCEDURE FOR SUSPECTED ALLERGIC CONTACT REACTION .................................... 66 
8.3.1 
In case of suspicion of allergic contact dermatitis ....................................... 66 
8.3.2 
In case of suspicion of immediate contact skin reaction (such as urticaria) 68 
8.4 
PROCEDURE FOR REPORTING A SERIOUS ADVERSE EVENT ......................................... 69 
8.5 
PROCEDURES FOR REPORTING PREGNANCIES ............................................................. 70 
9 
STATISTICAL METHODS PLANNED ................................................................................... 72 
9.1 
STATISTICAL AND ANALYTICAL PLANS ...................................................................... 72 
9.1.1 
Variables to be statistically analyzed ........................................................... 72 
9.1.2 
Populations analyzed, evaluability and limitations / evaluation of bias ...... 73 
9.1.3 
Data presentation and graphics ................................................................... 74 
9.1.4 
Statistical analyses ....................................................................................... 74 
9.1.5 
Interim analysis ............................................................................................ 75 
9.2 
SAMPLE SIZE DETERMINATION .................................................................................. 75 
9.2.1 
Historical data and assumptions .................................................................. 75 
9.2.2 
Sample size calculation ................................................................................ 75 
10 TRAINING / MONITORING / DATA MANAGEMENT / QUALITY ASSURANCE ........ 76 
10.1 PERSONNEL TRAINING ............................................................................................... 76 
10.2 CLINICAL MONITORING ............................................................................................. 76 
10.3 DATA MANAGEMENT ................................................................................................. 77 
10.4 QUALITY ASSURANCE / AUDIT / INSPECTION .............................................................. 77 
11 ETHICS AND GENERAL CLINICAL TRIAL CONDUCT CONSIDERATIONS ............. 78 
11.1 INSTITUTIONAL REVIEW BOARD (IRB) OR ETHICS COMMITTEE (EC)........................... 78 
11.2 ETHICAL CONDUCT OF THE CLINICAL TRIAL .............................................................. 78 
11.3 SUBJECT INFORMATION SHEET / INFORMED CONSENT ................................................ 78 
11.4 CONTRACTUAL REQUIREMENTS................................................................................. 79 
11.5 DATA COLLECTION AND ARCHIVING .......................................................................... 79 
11.5.1 
Data Collection ............................................................................................ 79 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 12 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
11.5.2 
Source documentation .................................................................................. 79 
11.5.3 
Archives ........................................................................................................ 80 
11.6 INSURANCE ............................................................................................................... 80 
12 REFERENCE LIST ..................................................................................................................... 81 
13 ATTACHMENTS ......................................................................................................................... 83 
13.1 APPENDIX 1 ............................................................................................................... 83 
13.2 APPENDIX 2 ............................................................................................................... 89 
13.3 APPENDIX 3 ............................................................................................................... 95 
 
List of Tables 
Table 1: Investigator’s Scar Global Assessment (SGA) ..................................................................... 55 
Table 2: Investigator’s preference in terms of overall scar severity ................................................... 55 
Table 3: Investigator’s global assessment of acne (IGA) .................................................................... 57 
Table 4: Skin roughness score ............................................................................................................. 57 
Table 5: Skin texture change score ...................................................................................................... 58 
 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 13 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
AE 
Adverse Event 
APT 
All Patients Treated (Safety Population) 
BPO 
Benzoyl peroxide 
CDMS 
Clinical Data Management System 
CPM 
Clinical Project Manager 
CRA 
Clinical Research Associate 
eCRF 
Electronic Case Report Form 
CRO 
Contract Research Organization 
DMP 
Data Management Plan 
EC 
Ethics Committee 
EDC 
Electronic Data Capture 
FSI 
First Subject In (first subject who signs the Informed Consent Form) 
GCP 
Good Clinical Practice 
GPRS 
General Packet Radio Service 
hCG 
Human chorionic gonadotropin 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IGA 
Investigator’s Global Assessment 
i.e. 
That is (Latin: id est) 
IRB 
Institutional Review Board 
ISF 
IUD 
Investigator Site File 
Intra Uterine Device 
ITT 
Intent-To-Treat 
LOCF 
LSI 
LSO 
Last Observation Carried Forward 
Last Subject In (Last subject who signs the Informed Consent Form) 
Last Subject Out (last subject last visit) 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMP 
Matrix-degrading metalloproteinases 
N/A 
Not Applicable 
OTC 
Over-The-Counter 
PIH 
Post-Inflammatory Hyperpigmentation 
PP 
Per Protocol 
PRO 
Patient Reported Outcome 
QA 
Quality Assurance 
QR code 
Quick Response code 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 14 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis  System (SAS Institute Inc., Cary, NC) 
SCARS 
Self-assessment of Clinical Acne-Related Scars 
SD 
Standard Deviation 
SGA 
Scars Global Assessment 
SIN 
Subject Identification Number 
SOC 
System Organ Class 
SOP 
SPF 
Standard Operating Procedure 
Sun Protection Factor 
UPT 
Urine Pregnancy Test 
UV 
Ultraviolet 
w 
Week 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 15 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
1 
SYNOPSIS 
 
Clinical trial title: Effect of Adapalene 0.3% - benzoyl peroxide 2.5% gel versus vehicle gel on 
the risk of formation of atrophic acne scars in moderate to severe acne subjects 
 
Short title: Adapalene 0.3% - benzoyl peroxide 2.5% gel and risk of formation of atrophic acne 
scars 
Project number: 
816 
Clinical trial phase: 
IV 
Clinical trial period 
(planned): 
Q2 2016 – Q4 2017 
Objective(s): 
 
The main objective of this trial is to evaluate the effect of 
Adapalene 0.3% - benzoyl peroxide (BPO) 2.5% gel versus 
vehicle gel on the risk of formation of atrophic acne scars in 
moderate to severe acne subjects. 
Methodology: 
 
This trials is composed of 2 parts: 
 
Part I: This is a multi-centre, international, randomized, 
investigator blinded, vehicle controlled trial using intra-
individual comparison (right half-face versus left half-face). 
 
 
All eligible subjects will have each half-face randomized to one 
of the two following treatments: 
- once-daily Adapalene 0.3% - BPO 2.5% gel (CD0271 
0.3%/CD1579 2.5% Gel, named Tactupump™ Forte in Canada, ). 
- once-daily “Adapalene 0.3% - BPO 2.5%” vehicle gel (Vehicle 
gel) 
 
Part II: This is an open-label trial. At the decision of the 
investigator based on his/her medical assessment of efficacy 
during part I (effect on acne lesions and/or acne scars) and if the 
subject agrees, the subjects will have the possibility to continue 
to be treated with once-daily Adapalene 0.3% - BPO 2.5% gel 
(CD0271 0.3%/CD1579 2.5% Gel / Tactupump™ Forte) for up to 
24 additional weeks on the whole face. 
 
 
Total number of planned 
subjects/sites:  
Approximate number of 
subjects/site:  
A total of 60 subjects will be enrolled at approximately 7 sites 
(8-15 subjects per site). 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 16 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
Clinical trial title: Effect of Adapalene 0.3% - benzoyl peroxide 2.5% gel versus vehicle gel on 
the risk of formation of atrophic acne scars in moderate to severe acne subjects 
 
Short title: Adapalene 0.3% - benzoyl peroxide 2.5% gel and risk of formation of atrophic acne 
scars 
Country(ies) involved: 
Canada, France 
Population and main 
inclusion criteria: 
 
Male or female subjects with moderate to severe acne vulgaris, 
age of 16 to 35 years inclusive, meeting specific 
inclusion/exclusion criteria. 
Clinical trial duration per 
subject 
  
The maximum trial duration for a subject is 48 weeks: 
Part I: 24 weeks 
Part II: 24 weeks 
 
 
Number of visits: 
 
Part I (8 visits): Baseline, W1, W4, W8, W12, W16, W20 and 
W24 
Part II (2 visits): W36 and W48 
Investigational product 
Name: 
 
Pharmaceutical form: 
Dose/concentration: 
Total daily dose: 
Mode and frequency of 
administration: 
Location of treated area: 
Duration of treatment: 
 
Tactupump™ Forte (in Canada) / CD0271 0.3%/CD1579 2.5% 
Gel 
Gel  
Adapalene 0.3% - BPO 2.5% 
2 pea-sized amounts for one half-face 
 
Topical, once-daily in the evening after washing 
Face 
24 weeks (part I) + 24 additional weeks (part II) 
Investigational comparator 
product: 
Name: 
Pharmaceutical form: 
Strength/concentration: 
Total daily dose: 
Mode and frequency of 
administration: 
Location of treated area: 
Duration of treatment:  
 
 
 
Vehicle gel (used only during part I) 
Gel 
N/A 
2 pea-sized amounts for one half-face 
 
Topical, once-daily in the evening after washing 
Face 
 
24 weeks  
Non-investigational product 
to be provided for the 
clinical trial: 
Cetaphil® DermaControl™ Oil Control Foam Wash, twice daily 
(once in the morning, once in the evening). 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 17 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
Clinical trial title: Effect of Adapalene 0.3% - benzoyl peroxide 2.5% gel versus vehicle gel on 
the risk of formation of atrophic acne scars in moderate to severe acne subjects 
 
Short title: Adapalene 0.3% - benzoyl peroxide 2.5% gel and risk of formation of atrophic acne 
scars 
 
Cetaphil® DermaControl™ Oil Control Moisturizer SPF 30 once 
daily in the morning after using Cetaphil® DermaControl™ Oil 
Control Foam Wash and applications as needed during the day. 
 
Both products are topical and will be used on the whole face for 
the whole duration of the trial (up to 48 weeks). 
Measurement criteria 
 
Efficacy 
 Atrophic acne scar count on each half-face at each visit. 
 Investigator’s scar global assessment (SGA) of each half-face 
at each visit on a scale from 0 (Clear) to 4 (Severe). 
 Investigator’s preference on overall scar severity (right vs. 
left) on a scale from -2 to 2 at week 12 and week 24, early 
termination during part I.  
 Non-inflammatory lesion (open and closed comedones), 
inflammatory lesion (papules, pustules) and nodule count on 
each half-face at each visit. 
 Investigator’s global assessment (IGA) of each half-face at 
each visit: severity of acne on a scale from 0 (Clear) to 4 
(Severe).  
 Investigator’s assessment of skin roughness of each half-face 
at Baseline, week 12, week 24, week 48, early termination. 
 Investigator’s assessment of skin texture change of each half-
face at week 12, week 24, week 48, early termination. 
 Quantitative evaluation of skin microrelief (skin replica) for 
each half-face at Baseline, week 24, week 48, early 
termination (if after week 8) (done at one selected site only). 
 
Safety 
 Adverse Events (AEs) throughout the trial. 
 Local tolerability scores (Erythema, Scaling, Dryness, 
Stinging/Burning) at each visit. 
 
Patient Reported Outcome (PRO) 
 Acne scar appearance using the SCARS questionnaire at 
Baseline, week 12, week 24, week 48, early termination for 
each half-face.  


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 18 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
Clinical trial title: Effect of Adapalene 0.3% - benzoyl peroxide 2.5% gel versus vehicle gel on 
the risk of formation of atrophic acne scars in moderate to severe acne subjects 
 
Short title: Adapalene 0.3% - benzoyl peroxide 2.5% gel and risk of formation of atrophic acne 
scars 
 Subject satisfaction questionnaire at week 24, week 48, early 
termination. 
 
Other 
 Photographs at Baseline, week 12, week 24 and week 48 
(done at selected sites only). 
Analysed variables 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Efficacy variables  
 
Primary efficacy endpoint 
Total atrophic acne scar count per half-face at week 24 
 
Secondary efficacy endpoints 
 Total atrophic acne scar count per half-face at each post-
baseline visit (except week 24) 
 Percent change from Baseline in total atrophic acne scar 
count per half-face at each post-baseline visit 
 SGA per half-face at each post-baseline visit 
 Investigator’s preference on overall scar severity (right vs. 
left) at week 12 and week 24/early termination during part I 
 Percent change from Baseline in total lesion count per half-
face at each post-baseline visit 
 Percent change from Baseline in inflammatory lesion count 
per half-face at each post-baseline visit 
 Percent change from Baseline in non-inflammatory lesion 
count per half-face at each post-baseline visit 
 IGA per half-face at each post-baseline visit 
 
Exploratory endpoints 
 Investigator’s assessment of skin roughness for each half-face 
at Baseline, week 12, week 24, week 48, early termination 
 Investigator’s assessment of skin texture change for each 
half-face at week 12, week 24, week 48, early termination 
 Skin microrelief variables: percent change from Baseline per 
half-face at week 24, week 48, early termination (if after 
week 8) 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 19 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
Clinical trial title: Effect of Adapalene 0.3% - benzoyl peroxide 2.5% gel versus vehicle gel on 
the risk of formation of atrophic acne scars in moderate to severe acne subjects 
 
Short title: Adapalene 0.3% - benzoyl peroxide 2.5% gel and risk of formation of atrophic acne 
scars 
 
 
 
Analysed variables 
(continued) 
 
 
Safety variables on Safety population 
 Incidence of Adverse Events 
 Local tolerability: percent of subjects across scores at each 
post-baseline visit 
 
 
PRO 
 Acne scar appearance using the SCARS questionnaire at 
Baseline, week 12, week 24, week 48, early termination, for 
each half-face  
 
 Subject satisfaction questionnaire at week 24, week 48, early 
termination 
 
Principal statistical methods 
and sample size calculation: 
 
The Per Protocol (PP) population will consist of all enrolled and 
randomized subjects, except subjects who have major deviations 
from the protocol. The Intent-to-Treat (ITT) population will 
consist of the entire population enrolled and randomized. The 
last observation carried forward (LOCF) method will be used to 
impute missing values of acne scar and lesion counts and global 
assessment scores. Analysis population definitions will be 
decided before the database lock and unblinding. 
 
The primary objective of this trial is to demonstrate the 
superiority of Adapalene 0.3% - BPO 2.5% gel compared to its 
vehicle, in terms of total atrophic acne scar count at week 24.  
 
The mean bilateral difference between products of primary 
efficacy endpoint will be analyzed by using the Wilcoxon Rank 
Signed test, testing the hypothesis of equality. The p-value will 
have to be inferior to 0.05 at week 24, on ITT/LOCF population.  
PP analysis will be also performed to assess the robustness of the 
results obtained on the ITT/LOCF population. 
 
The other efficacy variables of part I will be analyzed similarly 
as primary analysis on appropriate population. Each test will be 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 20 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
Clinical trial title: Effect of Adapalene 0.3% - benzoyl peroxide 2.5% gel versus vehicle gel on 
the risk of formation of atrophic acne scars in moderate to severe acne subjects 
 
Short title: Adapalene 0.3% - benzoyl peroxide 2.5% gel and risk of formation of atrophic acne 
scars 
two-sided, at the 0.050 significance level. 
 
The subject characteristics (previous medication, concomitant 
medication, demographics, baseline characteristics…), lesion 
counts, microrelief, adverse events, local tolerability and 
questionnaires, and all variables of part II will be summarized by 
descriptive statistics (usual statistics and frequency distribution). 
 
Results from a previous intra-individual trial designed as a right-
left comparison of Adapalene 0.1% - BPO 2.5% gel versus 
vehicle gel in acne subjects (protocol RD.03.SPR.40183E) 
showed a standard deviation (SD) of the bilateral differences in 
terms of total atrophic acne scar count at Week 24 of around 4.8 
with a mean bilateral difference around 2. 
Using the historical data mentioned above, 50 evaluable subjects 
will be required, with 80% power. To allow about 20% rate of 
subjects excluded from the analysis (drop out, lost to follow-up, 
etc.) at week 24, 60 subjects should be enrolled. 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 21 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
2 
BACKGROUND AND RATIONALE 
2.1 
MEDICAL BACKGROUND AND SHORT RATIONALE FOR THE CLINICAL TRIAL 
Acne vulgaris is a chronic, inflammatory skin disease of the pilosebaceous unit, affecting 
approximately 80% of young adults and adolescents (Kraining, et al., 1979) (Cunliffe, et al., 1979) 
(Usatine, et al., 1998) (Leyden, 1995). This is a polymorphic disease in which several types of 
lesions are usually present at the same time: primary lesions, found in active acne defined by the 
non-inflammatory and the inflammatory lesions; secondary lesions which came from the first ones 
and which are defined by scarrings and postinflammatory hyperpigmentation (PIH).  It can persist 
for years and may affect seriously the psychosocial development, resulting in emotional problems, 
withdrawal from society, and depression (Koo , et al., 1991). 
Even if the treatments are efficient in non-inflammatory and inflammatory lesions, secondary acne 
lesions are not well addressed by the treatments and remain the most unfortunate clinical outcome of 
acne (Layton, et al., 1994). Acne scars are not uniform and there are several subtypes.  Some are 
more hypertrophic and keloidal in appearance, while others could be more atrophic (Goodman, et al., 
2006(a)) (Goodman, et al., 2006(b)).  The severity of the acne scars is correlated with the acne grade 
and also with the delay between the start of the disease and the start of an adapted treatment (Layton, 
et al., 1994).  In her clinical evaluation of acne scarring, Layton indicated that facial scarring occurs 
to some degree in the majority of acne sufferers (95% of the population) even in the mild to 
moderate population. Although not universal, acne scars generally occur more with inflammatory 
acne lesions that were not properly treated (Layton, et al., 1997). Once established, acne scars are 
believed not to be treatable medically but invasive procedures could offer some improvement (Jacob, 
et al., 2001) (Jemec, et al., 2004) (Goodman, 2011). 
Loss of dermal matrix is a contributing factor in atrophic acne scars (Kang, et al., 2005).  This loss of 
dermal matrix consists in degradation of collagen produced by intracellular pathway activated by 
inflammation during the acne lesion formation (Kang, et al., 2005) (Trivedi, 2006).  This leads to the 
transcription factor activation coding for matrix-degrading metalloproteinases (MMPs). MMPs 
degrade extracellular matrix molecules during physiological and pathological tissue remodeling. 
Three MMPs (MMP-1 [collagenase], MMP-3 [stromelysin] that can initiate collagen degradation and 
MMP-9 [gelatinase] that can further degrade collagen fragments) have been shown to be increased in 
inflammatory acne lesion in vivo (Kang, et al., 2005) (Trivedi, 2006) (Fisher, et al., 2000) 
(Papakonstantinou, et al., 2005). The same enzymes are involved in the remodelling of the dermal 
matrix in the photoaging process (Kang, et al., 1997) (Kang, et al., 1998) (Fisher, et al., 2000). 
Over the past decades, significant evidence has been accumulated that topical retinoids can stimulate 
dermal fibroblasts to produce more procollagen in photoaged skin (Kang, et al., 1997) (Kang, et al., 
1998) (Fisher, et al., 2000).  Type I and type III procollagen are reduced in photodamaged skin but it 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 22 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
has been demonstrated that isotretinoin, either oral or topical, protects against UV-induced loss of 
procollagen, leading to MMP-1, 3 and MMP-9 decrease in relation to the duration of the treatment 
(Kang, et al., 1997) (Kang, et al., 1998) (Fisher, et al., 2000).  This increase in collagen production is 
clinically appreciated as effacement of wrinkles. After 24 weeks of treatment with topical retinoid, 
an increase of the epidermal thickness has been observed (Griffiths, et al., 1995) (Kang, et al., 2001)  
(Philips, et al., 2002). Results generally start to be seen over a few weeks, but as the deposition of 
new collagen takes place slowly, the skin texture does continue to improve over a 12 month period 
(Fabbrocini, et al., 2010).  Adapalene gel 0.1% and 0.3% formulations have been demonstrated to 
treat actinic keratoses and solar lentigines and to improve fine and coarse wrinkles, mottled 
hyperpigmentation, and sallow complexion (Kang, et al., 2003). As photodamage lesions and 
atrophic acne scars are partially linked to a dermal matrix loss, a potential effect of Adapalene-
benzoyl peroxide fixed-dose combination (Adapalene - BPO) to prevent secondary acne lesions 
(scars) of occurring and/or to improve the pre-existing ones might exist.  
Adapalene 0.3% - BPO 2.5% gel is efficacious to treat moderate to severe acne (protocol No.: 
RD.03.SPR18240) with a trend of numerical superiority compared to Adapalene 0.1% - BPO 2.5% 
gel in subjects with severe acne.  
 
An exploratory trial (Protocol No.: RD.03.SPR.40183E) has been performed and has shown that over 
a 24 week period treatment, Adapalene 0.1% - BPO 2.5% reduced the inflammatory and non-
inflammatory primary lesions more than the vehicle but also stabilized acne scar counts whereas 
scars continued to increase with vehicle. Moreover the scar global assessment by the investigator 
improved with the combination Adapalene - BPO whereas it remained stable with the vehicle. This 
suggests that the combination Adapalene - BPO both prevents the formation of new acne scars by 
reducing the number of primary lesions and improves the appearance of pre-existing scars.  
It is hypothesized that the treatment effect on acne scars might be stronger with the more 
concentrated combination Adapalene 0.3% - BPO 2.5% gel. 
This controlled clinical trial is designed to evaluate the effect of Adapalene 0.3% - BPO 2.5% gel 
compared with its vehicle in subjects with moderate to severe acne vulgaris on the risk of formation 
of acne scars and to improve the appearance of pre-existing ones. 
 
At the decision of the investigator based on his/her medical assessment of efficacy during part I 
(effect on acne lesions and/or acne scars) and if the subject agrees, the subject may enter part II of 
the trial to continue using Adapalene 0.3% - BPO 2.5% gel for up to 24 additional weeks on the 
whole face. 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 23 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
2.2 
INVESTIGATIONAL PRODUCT PROFILE 
The product used in this clinical trial (Adapalene 0.3% - BPO 2.5% gel) is marketed under the name 
Tactupump™ Forte in Canada. Adapalene 0.3% - BPO 2.5% gel is well tolerated in subjects with 
acne vulgaris. See Canadian product monograph for detailed safety information.  
2.3 
RISK/BENEFIT ASSESSMENT 
2.3.1 Risk-benefit statement related to the clinical trial drugs 
 
Adapalene 0.3% - BPO 2.5% gel (marketed under the name Tactupump™ Forte in Canada) is a 
commercial product in Canada and will be used according to the approved Canadian indications and 
usage.  Warnings and precautions with Adapalene 0.3% - BPO 2.5% gel are well known and 
documented in the Canadian product monograph. For more details regarding the clinical adverse 
reactions and/or the post-marketing experience, please refer to the Canadian product monograph. 
 
2.3.2 Risk-benefit statement related to the clinical trial 
 
This is a vehicle controlled trial using intra-individual comparison (right half-face versus left half-
face) without direct benefit for the subject. 
 
Adapalene 0.1% - BPO 2.5% (marketed under the name Tactupump™ in Canada and Epiduo™ in 
France) is an established and very widely used marketed product and considered standard of care by 
many physicians and expert bodies for the treatment of acne vulgaris.  
The same safety profile with a long-term use is expected with Adapalene 0.3% - BPO 2.5% than 
with Adapalene 0.1% - BPO 2.5%. It is therefore considered that exposure to the treatment over 12 
months is covered by long-term safety data for the products Adapalene 0.3% and the combination of 
Adapalene 0.1% - BPO 2.5% which have shown that the safety profile remains stable with a long-
term use.  
 
Treatment-related adverse reactions typically associated with use of Adapalene 0.3% - BPO 2.5% 
include mild to moderate application site reactions, such as skin irritation characterized by scaling, 
dryness, erythema, and burning/stinging. These reactions usually occur early in the treatment, and 
tend to gradually lessen over time. 
 
To allow the subject to be treated on the whole face in case of a dramatic difference between right 
and left sides, a subject will stop the trial at the discretion of the investigator if the global assessment 
of the scars shows a marked asymmetry in scar severity between both half-faces at two consecutive 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 24 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
visits. In case the subject has prematurely discontinued the study during part I, s/he cannot enter part 
II. 
 
Any subject is free to discontinue his/her participation in this clinical trial at any time and for 
whatever reason, specified or unspecified, and without any prejudice.  No constraints are to be 
imposed on the subject, and when appropriate, a subject may be treated with other conventional 
therapy when clinically indicated. 
 
No invasive methods will be conducted during this trial. 
Subjects will be followed (especially for Adverse events) regularly during all the trial, approximately 
once a month for the first 24 weeks (part I) and every 12 weeks thereafter (part II). 
 
Consequently, based on available safety data and the proposed trial design, no safety issues others 
than those reported in the Canadian product monograph are expected following topical 
administration of Adapalene 0.3% - BPO 2.5% or its vehicle. 
 
 
3 
CLINICAL TRIAL OBJECTIVES AND CLINICAL HYPOTHESIS 
3.1 
CLINICAL TRIALS OBJECTIVES 
The main objective of this clinical trial is to evaluate the effect of Adapalene 0.3% - BPO 2.5% 
compared to its vehicle on the risk of formation of atrophic acne scars after 24 weeks of treatment in 
moderate to severe acne subjects assessed by atrophic acne scars count. 
 
Safety will also be evaluated up to 48 weeks. 
3.2 
CLINICAL HYPOTHESIS 
Acne scars being a consequence of inflammatory lesions, treatment of acne with Adapalene 0.3% - 
BPO 2.5% gel should prevent occurrence of new scars as shown in previous trials with Adapalene 
0.1% - BPO 2.5% gel (Protocol No.: RD.03.SPR.40183E) and with Adapalene 0.3% - BPO 2.5% 
(Protocol No.: RD.03.SPR18240, which has shown marked effects on inflammatory lesions). 
Formation of atrophic acne scars may be due to dermal matrix loss (degradation of collagen) (Kang, 
et al., 2005). Significant evidence has been accumulated that topical retinoids can stimulate dermal 
fibroblasts to produce more procollagen in photoaged skin (Kang, et al., 1997) (Kang, et al., 1998) 
(Fisher, et al., 2000). As atrophic acne scars are linked to the same process of dermal matrix loss as 
photodamage lesions, we hypothesize a potential effect of Adapalene 0.3% - BPO 2.5% gel on 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 25 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
atrophic acne scars. This was also suggested in a preliminary trial with Adapalene 0.1% - BPO 2.5% 
gel.  
Since the subject may continue treatment for 24 additional weeks, it will also be possible to continue 
assessing the skin texture over this time period. Indeed, as the deposition of new collagen takes place 
slowly, the skin texture will continue to improve over this 48-week period. 
As shown in subjects with photodamaged skin, the retinoid included in Adapalene 0.3% - BPO 2.5% 
gel might have a positive effect on cosmetic outcomes in younger subjects. 
 
 
4 
SELECTION AND DISPOSITION OF CLINICAL TRIAL POPULATION 
4.1 
NUMBER OF SUBJECTS 
A total of 60 subjects with moderate to severe acne vulgaris and atrophic acne scars will be enrolled 
at approximately 7 sites located in Canada and France.  
4.2 
CLINICAL TRIAL POPULATION CHARACTERISTICS 
Subjects who meet all of the following criteria will be eligible for the clinical trial.  
 
4.2.1 Inclusion criteria 
 
In order to be eligible for the clinical trial, the subject must meet all of the following inclusion 
criteria: 
 
1. 
Male or female subject aged 16 to 35 years inclusive 
2. 
Subject with clinical diagnosis of moderate to severe acne vulgaris on the face defined by: 
(a) Investigator’s Global Assessment score of 3 or 4, with same score on both sides; and 
(b) A minimum of 25 inflammatory lesions (papules and pustules) in total, with at least 10 on 
each side (excluding the nose); and 
(c) No more than two acne nodules (≥ 1 cm); and 
(d) A minimum of 10 atrophic acne scars in total (upper than 2 mm) (excluding the nose).  
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 26 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
3. 
Subject with a symmetric number of  
(a) both inflammatory and non-inflammatory lesions on the whole face, and 
(b) atrophic acne scars on the whole face 
i.e. there are no more than twice as many lesions of each type on one half of the face than on the 
other half. 
4. 
Subject with skin phototype of I to IV on Fitzpatrick’s scale (Fitzpatrick, et al., 1993). 
5. 
Female of childbearing potential with a negative urine pregnancy test (UPT) at the baseline 
visit.  
6. 
Female subjects of childbearing potential must practice an effective method of contraception 
during the clinical trial and at least 1 month after the last clinical trial treatment application: 
medical contraception [combined oral contraceptives (estrogens and progesterone) or  
implanted or injectable contraceptives] with stable dose for 1 month prior to clinical trial entry, 
bilateral tubal ligation, hormonal Intra-Uterine Device (IUD) inserted at least 1 month prior to 
clinical trial entry, strict abstinence (1 month prior to trial entry and agrees to continue for the 
duration of the trial),  condom with spermicide, vasectomized partner (for at least 3 months 
prior to clinical trial entry). 
7. 
Female of non-childbearing potential, eg: post-menopausal (absence of menstrual bleeding for 
one year prior to clinical trial entry, without any other medical reason), hysterectomy, bilateral 
oophorectomy. 
8. 
Subject having read, understood and signed the approved Informed Consent Form (ICF) prior 
to any participation in the clinical trial. Subjects under 18 years of age having signed an Assent 
Form to participate in the clinical trial and their parent(s) or legal representative having read 
and signed the Informed Consent Form prior to any clinical trial related procedure. 
9. 
Subject willing and able to comply with the requirements of the trial protocol, in particular, 
subject must adhere to the visit schedule, concomitant therapy prohibitions, and must be 
compliant to the treatment. 
10. 
For Canada: Subject informed of the terms pertaining to the Personal Information Protection 
and Electronic Documents Act (PIPEDA): the subject is willing to share personal information 
and data and he/she has provided authorization by signing the ICF.  
11. For France: Subject covered by a National Social Security System. 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 27 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
4.2.2 Exclusion criteria 
 
Any subject who meets one or more of the following criteria will not be included in this clinical trial.  
 
1. 
Subject with acne conglobata, acne fulminans, secondary acne (chloracne, drug-induced acne, 
etc.), nodulo cystic acne, acne requiring systemic treatment. 
2. 
Prior failure to treatment with Tactupump™ Forte (Adapalene 0.3% - BPO 2.5%). 
3. 
Subject with more than 3 excoriated acne lesions. 
4. 
Subject with skin abraded on the treated area or affected by eczema, seborrhoeic dermatitis, 
cuts or sunburn. 
5. 
Female subject who is pregnant, nursing or planning a pregnancy during the trial or within one 
month after the last trial treatment application. 
6. 
Female subject who is planning to change her contraceptive method or hormone replacement 
therapy during the trial. 
7. 
Subject with known impaired hepatic or renal functions. 
8. 
Male subject with a beard or facial hair, which would interfere with the clinical trial 
evaluations or clinical trial procedures. 
9. 
Subject having received at least one of the following topical treatments on the treated area: 
 
Corticosteroids, antibiotics, benzoyl peroxide, azelaic acid, hydroxyacids, 
Zinc containing treatments, antibacterials, antiseptics, other anti-inflammatory 
drugs or other acne treatments (for example, cosmetic products or salicylic 
acid treatments are forbidden if used to treat acne) 
Within 2 weeks 
 
Retinoids 
Within 4 weeks 
 
Cosmetic/aesthetic procedures on the face (e.g., peeling, comedone 
extraction, desquamating, or abrasive agents, adhesive cleansing strips) 
Within 1 week 
 
Photodynamic therapy, laser therapy, microdermabrasion for acne 
Within 3 months 
10. 
Subject having received at least one of the following  systemic treatments: 
 
Corticosteroids (except locally acting corticosteroids such as inhaled or 
intrathecal or dermal application at distance from the face), antibiotics (except 
penicillin)  
Within 1 month 
 
Spironolactone / Drospirenone (except if at a stable dose for at least 3 
months for drospirenone) 
Within 3 months 
 
Oral retinoids 
Within 6 months 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 28 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
 
Cyproterone acetate / Chlormadinone acetate 
Within 6 months 
 
Immunomodulators  
Within 3 months 
11. 
Subject with a condition or who is in a situation which, in the investigator’s opinion, may put 
the subject at risk, may confound the trial results, or may interfere with the subject’s 
participation in the trial. 
12. 
Subject who is at risk in terms of precautions, warnings, and contraindications for the 
investigational products (see Product Monograph for Tactupump™ Forte). 
13. 
Subject with known or suspected allergy to the investigational products (see Product 
Monograph for Tactupump™ Forte). 
14. 
Subject who has participated in another investigational product, cosmetic or device research 
trial within 30 days of enrolment OR is in an exclusion period from a previous clinical trial. 
15. 
Subject who has used tanning booths or lamps or who had excessive ultraviolet (UV) radiation 
exposure within 1 month prior to clinical trial entry or who foresees intensive UV exposure 
during the trial (mountain sports, UV radiation, sunbathing, etc...). 
16. 
Adult subject under guardianship, hospitalised subject in a public or private institution for a 
reason other than the research, and subject deprived of his/her freedom. 
17. 
Subject who is unable to communicate or cooperate with the investigator due to language 
problems, poor mental development, or impaired cerebral function. 
4.3 
PRIOR AND CONCOMITANT THERAPIES 
4.3.1 Definition 
 
Information on previous treatments/procedures that have been stopped within the 6 months preceding 
the baseline visit and that may have an impact on inclusion/exclusion criteria should be recorded in 
the eCRF. 
Concomitant therapies are defined as follows: 
 any existing therapies ongoing at the time of the first investigational product application, or 
 any changes to existing therapies (such as changes in dose or formulation) during the course 
of the clinical trial, or 
 any new therapies received by the subject since the first investigational product application 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 29 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
4.3.2 Categories 
 
The following two categories are to be considered for prior and concomitant therapies:  
 Drugs/therapies including but not limited to, prescription, over-the-counter (OTC), birth 
control pills/patches/hormonal devices, vitamins, moisturizers, sunscreens, herbal 
medicines/supplements, and homeopathic preparations. 
 Medical and surgical procedures including, but not limited to, laser/radiation procedures, 
dermal fillers, X-rays, etc. 
 
4.3.3 Recording 
 
Previous and concomitant therapies are to be recorded on the Drugs/Therapies Form (for 
drugs/therapies) and/or on the Medical and Surgical Procedures form (for medical/surgical 
procedures) in the eCRF. 
Concomitant therapies are to be recorded, reviewed, and updated at each visit. Every attempt should 
be made to keep concomitant therapy dosing and regimen constant during the trial. 
Any new concomitant therapy or modification of an existing therapy may be linked to an adverse 
event (AE).  A corresponding Adverse Event Form must be completed to account for the change in 
therapy, except in some cases such as therapy used for prophylaxis, dose modification for a chronic 
condition, etc. 
 
4.3.4 Authorized therapies during the clinical trial  
 
Unless listed under the exclusion criteria (section 4.2.2 items 9 and 10) or in prohibited therapies 
(section 4.3.5), all therapies are authorized. 
Subject may use moisturizer as required for the symptomatic relief of skin dryness or irritation (use 
of moisturizer other than the one provided for this clinical trial will be captured into the eCRF as 
concomitant therapy). 
Oral vitamin A supplement (up to the recommended daily allowance) and plain penicillin are 
acceptable. 
Systemic anti-inflammatory medication up to 21 days of treatment in total is also acceptable; 
however, it should be avoided for 1 week prior to the week 24 visit (primary endpoint assessment). 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 30 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
4.3.5 Prohibited therapies during the clinical trial  
 
The following drugs/procedures are prohibited because they may interfere with the efficacy/safety 
assessment of the investigational product, or because they may interact with the metabolism of the 
investigational product: 
 All topical or systemic drugs/procedures listed in exclusion criteria (section 4.2.2, items 9 and 
10) 
 Any irritating topical products (medicated or abrasive soaps and cleansers, soaps and 
cosmetics that have strong skin-drying effect and products with high concentrations of alcohol, 
astringents, spices, or limes) 
 Any other drugs/procedures which in the investigator’s judgement are liable to interfere or 
interact with the efficacy or safety of Tactupump™  Forte (Adapalene 0.3% - BPO 2.5%). 
If prohibited therapies become a necessary treatment for the safety or best interest of the subject, the 
sponsor should be notified to discuss possible alternatives prior to administration of a prohibited 
therapy and to discuss the pertinence and the modalities for the subject to continue in the clinical 
trial. 
4.4 
PROCEDURES / REASONS FOR DISCONTINUATION 
An investigator may decide to discontinue a subject from the clinical trial for safety reasons. 
Although the importance of completing the entire clinical trial should be explained to the subject by 
the clinical trial personnel, any subject is free to discontinue his/her participation in this clinical trial 
at any time and for whatever reason, specified or unspecified, and without prejudice.  
 
Subjects who discontinue the clinical trial prematurely should be fully evaluated, whenever possible. 
The procedures corresponding to the next theoretical visit should be performed (for instance, if a 
subject discontinues at week 10, complete the week 12 visit procedures). Additional final procedures 
will be conducted as indicated in the trial flow chart section 5.4. The appropriate eCRF pages should 
be completed. 
 
For all subjects who prematurely discontinue the clinical trial, the reason must be carefully 
documented by the investigator on the Exit Form, and, if applicable, on the Adverse Event Form for 
discontinuation due to an AE.  
 
A subject who has been randomized and assigned a kit number/randomization number cannot be 
replaced by another subject if he/she discontinues the clinical trial for any reason. 
  
In the case of early termination, the investigator should ensure that the subject receives appropriate 
therapy for his/her condition. 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 31 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
 
The sponsor may also decide to prematurely terminate or suspend the clinical trial or the 
participation of a subject in the clinical trial. 
 
All data gathered on the subject prior to termination should be made available to the sponsor. 
 
Reasons for clinical trial completion/discontinuation, as listed on the Exit Form of the eCRF are 
described below. Note that there will be 2 separate Exit Forms, one completed at the end of part I (or 
early termination during part I), and one completed at the end of part II (or early termination during 
part II).  
 
Normal study  Completion 
Subject completes the clinical trial as planned in the protocol. 
Adverse Event 
Complete eCRF Adverse Event Form. 
Subject's Request 
Includes consent withdrawal, subject relocation, subject has a 
conflicting obligation. Explain the reason for withdrawal in the 
comments section of the eCRF Exit Form. 
Protocol Violation 
Explain the violation in the comments section of the eCRF Exit 
Form 
Lost to Follow-up 
Confirmed with 2 documented phone calls and a certified letter 
(delivery receipt requested) without response.  Explain in the 
comments section of the eCRF Exit Form. 
Other 
This category is to be used for a subject who discontinues for a 
reason other than those specified in the predefined categories 
above. In case the subject discontinues because of a marked 
asymmetry in scar severity between both half-faces at two 
consecutive visits (see section 2.3.2), this category should be 
chosen too. 
Explain the reason for discontinuation in the comments section 
of eCRF Exit Form. 
Pregnancy 
Withdraw the subject from the clinical trial following the 
procedure described in the protocol (see section 8.5). 
If reason for discontinuation is “subject request” or “other”, the subject must be questioned to rule 
out the possibility of an AE; this should be documented in the eCRF. 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 32 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
5 
INVESTIGATIONAL PLAN 
5.1 
OVERALL CLINICAL TRIAL DESIGN 
During part I, this clinical trial will be conducted as a multi-centre, randomized, investigator-blinded, 
vehicle controlled trial using intra-individual comparison (right half-face versus left half-face) 
involving subjects aged 16 to 35 years inclusive with moderate to severe acne vulgaris and atrophic 
acne scars, and meeting other specific eligibility criteria. 
 
A total of 60 subjects will be enrolled at approximately 7 sites located in Canada and France. 
Approximately 8-15 subjects are planned at each site. 
 
Subjects will be enrolled at baseline and treated for 24 weeks and will have each half-face 
randomized to one of the two following treatments: 
 
once-daily Adapalene 0.3% - BPO 2.5% gel (Tactupump™  Forte / CD0271 0.3%/CD1579 
2.5% Gel). 
 
once-daily “Adapalene 0.3% - BPO 2.5%” vehicle gel (Vehicle gel). 
 
During part I, there will be 8 trial visits: at baseline, week 1 (± 1 day), week 4 (± 3 days), week 8 (± 
3 days), week 12 (± 1 week), week 16 (±1 week), week 20 (±1 week) and week 24 (±1 week).  
 
At the end of part I, at the decision of the investigator based on his/her medical assessment of 
efficacy during part I (effect on acne lesions and/or acne scars) and if the subject agrees, the subjects 
will have the possibility to continue treatment with Adapalene 0.3% - BPO 2.5% gel (Tactupump™ 
Forte / CD0271 0.3%/CD1579 2.5% Gel) for 12 or 24 additional weeks on the whole face. This 
second part of the clinical trial (part II) will be conducted as a multi-centre, open-label trial. 
 
During part II, there will be 2 trial visits: week 36 (±2 weeks) and week 48 (±2 weeks). 
5.2 
DISCUSSION OF CLINICAL TRIAL DESIGN 
This clinical trial will assess the effect of a marketed product (under the name Tactupump™ Forte in 
Canada), used according to its labeling information (indication, selected population, dose regimen) 
and is therefore classified as a Phase IV trial. 
No topical product has been described to have an efficacy on the risk of formation of atrophic acne 
scars, which justifies a vehicle controlled design. Intra-individual comparisons (split-face trial) shall 
minimize inter-individual variability (increase of study power whilst minimizing the number of 
subjects). 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 33 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
Since acne is a chronic and long-lasting skin condition, the sponsor considers that 6 months 
treatment will be sufficient to obtain clinical effect on the basis of the following points: 
 
Scarring appears secondarily to primary lesions of acne defined by non-inflammatory and/or 
inflammatory lesions and may correspond to a resolution of these primary lesions;  
 
It is generally agreed in acne clinical trials that 3 months treatment is sufficient to evaluate 
the efficacy on the primary lesions of acne. Consequently, to investigate their resolution, the duration 
of treatment has to be increased to 6 months;  
 
To observe a relevant effect on scars, a duration of at least 6 months is required. 
In addition, some subjects may continue treatment for up to 24 additional weeks with Adapalene 
0.3% - BPO 2.5% to improve acne and scar aspect (due to treatment with vehicle).  
 
This clinical trial should allow comparing the efficacy on the risk of formation of atrophic acne scars 
of the investigational product Adapalene 0.3% - BPO 2.5% to its vehicle. 
5.3 
CLINICAL TRIAL DURATION AND TERMINATION 
The average planned period for the clinical trial (from First Subject In (FSI) to Last Subject Out 
(LSO) is 20 months. The end date of the clinical trial will be the date of the last visit of the last 
subject (LSO) who participates in the clinical trial. 
The planned duration of recruitment (i.e. From FSI to Last Subject In (LSI)) is approximately 8 
months. 
The clinical trial may be terminated by the investigator at his/her clinical trial site at any time with 
appropriate notification to GALDERMA R&D. Likewise, GALDERMA R&D may terminate the 
clinical trial and/or the participation of a clinical trial site with appropriate notification. 
 
The expected duration of subject participation is up to 48 weeks: 
- 
Part I: 24 weeks 
- 
Part II: 24 weeks 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 34 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
5.4 
CLINICAL TRIAL FLOW CHART 
 
PROCEDURES 
CLINICAL TRIAL VISITS 
Part I 
Part II 
Visit 1 
Visit 
2 
Visit 
3 
Visit 
4 
Visit 
5 
Visit 
6 
Visit 
7 
Visit 8 
Visit 9 
Visit 10 
Baseline 
 
Week 
1 
(±1 
d) 
Week 
4 
(±3 
d) 
Week 
8 
(±3 
d) 
Week 
12 
(±1 
w) 
Week 
16 
(±1 
w) 
Week 
20 
(±1 
w) 
Week 
24 
(±1 w) 
Week 
36 
(±2 w)  
Week 
48 
(±2 w) 
Informed Consent/Photography 
Consentb 
X 
 
 
 
 
 
 
X 
 
 
Inclusion/Exclusion Criteria 
X 
 
 
 
 
 
 
 
 
 
Demographics/ Relevant medical 
history/ Prior therapiesc 
X 
 
 
 
 
 
 
 
 
 
Urine Pregnancy test (UPT)d 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Atrophic acne scar count 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Investigator’s  Scar Global 
Assessment  (SGA) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Investigator’s preference on overall 
scar severity 
 
 
 
 
X 
 
 
Xa 
 
 
Acne lesion counte 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Investigator’s  Global Assessment 
(IGA)  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Skin roughness score 
X 
 
 
 
X 
 
 
Xa 
 
Xj 
Skin texture change score 
 
 
 
 
X 
 
 
Xa 
 
Xj 
Skin microrelief (skin replica)f 
X 
 
 
 
 
 
 
Xi. 
 
Xj 
SCARS questionnaire 
X 
 
 
 
X 
 
 
Xa 
 
Xj 
Subject satisfaction questionnaire 
 
 
 
 
 
 
 
Xa 
 
Xj 
Photographsb 
X 
 
 
 
X 
 
 
X 
 
Xj 
Concomitant therapies 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse eventsg / local tolerability 
assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispensation of investigational 
products  
X 
 
X 
X 
X 
X 
X 
X 
X 
 
Dispensation of non-investigational 
products 
X 
 
 
X 
 
X 
 
X 
X 
 
Dispensation of “study companion” 
tableth 
X 
 
 
 
 
 
 
 
 
 
Part I: Review of treatment 
compliance / return of “study 
companion” tableth and download 
of videos 
 
X 
X 
X 
X 
X 
X 
X 
 
 
Part II: Review of treatment 
compliance 
 
 
 
 
 
 
 
 
X 
X 
Return of investigational products  
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Exit Form part Ia 
 
 
 
 
 
 
 
Xa 
 
 
Exit Form part IIj 
 
 
 
 
 
 
 
 
 
Xj 
a.  
To be performed at week 24 or before in case of early termination 
b.  Photography consent and standardized photography at selected sites only. 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 35 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
c.  
Only prior therapies that were stopped within 6 months of the baseline visit and that may have an impact on inclusion/exclusion 
criteria should be recorded. Treatment that continues after baseline should be recorded on the Concomitant Treatment Form of the 
eCRF. 
d.  UPT will be sourced directly by the investigational sites and will have a sensitivity down to at least 25 IU/L for hCG. UPT is 
mandatory at baseline, week 24and week 48 or early termination.  
e.  Papules, pustules, nodules, open and closed comedones will be counted. 
f.  
Skin replica will be performed at one selected site only. 
g.  Adverse event onsets after subject’s signature of the Informed Consent Form should be recorded on the AE Form of the eCRF. 
h.  “Study companion” is a tablet which will be given to the subject during part I to assess his/her treatment compliance. 
i.  
To be performed at week 24 or before in case early termination occurs after week 8 (during part I). 
j.  
To be performed/completed at week 48 or before in case of early termination from part II 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 36 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
5.5 
CLINICAL TRIAL VISIT DESCRIPTION AND PROCEDURES 
5.5.1 Visit 1 (baseline) (part I) 
 
1. Explain the nature and the constraints of the clinical trial to the subject and to his/her parent(s) 
or guardian if the subject is under the age of 18.   
2. If a female subject of childbearing potential agrees to participate to the clinical trial, make sure 
she is using the requiring method(s) of contraception. 
3. Ensure the subject (and parent/guardian for subjects under the age of 18) has read, understood, 
dated and signed the approved Informed Consent Form (ICF).  
4. Give a dated and signed copy of the ICF to each subject and parent/guardian if applicable. 
5. Log into the electronic Case Report Form (eCRF) to get a Subject Identification Number (SIN) 
6. Question the subject about demography (birthdate, race, skin phototype, gender), relevant 
medical history, prior therapies (stopped within 6 months of the baseline visit and that may have 
an impact on the inclusion/exclusion criteria) and concomitant therapies. 
7. Inform subject about authorized and prohibited concomitant therapies.  
8. Check inclusion/exclusion criteria (see sections 4.2.1 and 4.2.2). 
9. Conduct a urine pregnancy test (UPT) for female subjects of childbearing potential. 
10. Count atrophic acne scars of each half-face (see section 7.1.1). 
11. Perform an Investigator’s Scar Global Assessment (SGA) of each half-face (see section 7.1.2). 
12. Count inflammatory, non-inflammatory acne lesions and nodules of each half-face (see section 
7.1.4). 
13. Perform an Investigator’s Global Assessment (IGA) of each half-face (see section 7.1.5). 
14. Assess the skin roughness score of each half-face (see section 7.1.6). 
15. Perform 
the 
baseline 
Local 
Tolerability 
Assessment 
(erythema, 
dryness, 
scaling, 
stinging/burning; see Section 7.2.1). Note: Stinging/burning at the baseline visit should be 
assessed as None (0). 
16. For selected sites only (and only if subject and parent/guardian accept through the approved ICF, 
if applicable), take photographs of the face according to the provided procedure. 
17. For selected sites only, make skin replica for each half-face (if consent given) (see section 
7.1.8). 
18. Provide guidance on the SCARS questionnaire and ask the subject to fill it out for each half-face 
(see Appendix 1). 
19. Question the subject about the occurrence of any adverse events (AEs) by asking an open ended 
question taking care not to influence the subject’s answer, such as: “have you had any new 
symptoms, injuries, illness or side-effects or worsening of pre-existing conditions?” Record all 
events as appropriate on the corresponding AE eCRF pages. 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 37 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
20. If the subject is eligible, assign a kit number (see specific section 6.1.2) (to be reported on the 
prescription form). 
21. The product dispenser (person in charge of products dispensation and not involved in the clinical 
trial measurement criteria) will: 
a. 
Dispense to the subject the baseline investigational products from the adequate subject 
kit according to the Prescription Form. 
b. Affix the tear-off portion of the labels on the product dispensation log. 
c. 
Dispense to the subject the associated non-investigational products with explanations 
how and when to use them. 
d. Dispense the subject participation card to the subject. 
e. 
Dispense the “study companion” tablet to the subject, with appropriate written and verbal 
instructions. 
f. 
Provide appropriate verbal and written instructions on how to properly use the 
investigational products. The first application of investigational products will be 
conducted by the subject under the direction of the product dispenser before leaving the 
investigational site. 
g. Remind the subject to not apply the investigational products the first evening. 
h. Emphasize the importance of complying with the given instructions and treatments; 
instruct the subject to bring back the “study companion” tablet at the next visit. 
i. 
For all female subjects, emphasize the guidelines about contraception and risks in case of 
pregnancy. 
22. 
Schedule the next follow up visit in one week ± 1 day 
 
5.5.2 Visit 2 (week 1) (part I) 
 
1. Question the subject about occurrence of adverse events (AEs) and assess local tolerability (see 
section 7.2). Record occurrence of any events and/or any changes in events that were ongoing at 
the previous clinical trial visit. Document all changes in the eCRF. 
2. Enquire whether any concomitant therapies have been added, stopped, or changed since the 
subject’s last visit. Document all changes in the eCRF. 
3. Count atrophic acne scars of each half-face (see section 7.1.1). 
4. Perform an Investigator’s Scar Global Assessment (SGA) of each half-face (see section 7.1.2). 
5. Count inflammatory, non-inflammatory acne lesions and nodules of each half-face (see section 
7.1.4). 
6. Perform an Investigator’s Global Assessment (IGA) of each half-face (see section 7.1.5). 
7. The product dispenser will: 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 38 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
a. 
Assess subject’s compliance based on the subject’s compliance report available on 
Triacys website and discussion with the subject and report in the eCRF any missing or 
incomplete product application record as indicated in the product dispensation log. 
b. Download data from the “Study Companion” tablet. 
c. 
Emphasize again the importance of complying with the given instructions and 
treatments; instruct the subject to bring back the dispensed investigational products 
together with the “study companion” tablet at the next visit. 
d. For all female subjects, emphasize the guidelines about contraception and risks in case of 
pregnancy. 
8. Schedule the next follow up visit in three weeks ± 3 days 
 
5.5.3 Visit 3 (week 4), 4 (week 8), 6 (week 16) and 7 (week 20)  (part I) 
 
1. Question the subject about occurrence of adverse events (AEs) and assess local tolerability (see 
section 7.2). Record occurrence of any events and/or any changes in events that were ongoing at 
the previous clinical trial visit. Document all changes in the eCRF. 
2. Enquire whether any concomitant therapies have been added, stopped, or changed since the 
subject’s last visit. Document all changes in the eCRF. 
3. Conduct a urine pregnancy test (UPT) for female subjects of childbearing potential. 
4. Count atrophic acne scars of each half-face (see section 7.1.1). 
5. Perform an Investigator’s Scar Global Assessment (SGA) of each half-face (see section 7.1.2). 
6. Count inflammatory, non-inflammatory acne lesions and nodules of each half-face (see section 
7.1.4). 
7. Perform an Investigator’s Global Assessment (IGA) of each half-face (see section 7.1.5). 
8. The product dispenser will: 
a. 
Check the returned investigational products. 
b. Assess subject’s compliance based on the subject’s compliance report available on 
Triacys website and discussion with the subject and report in the eCRF any missing or 
incomplete product application record as indicated in the product dispensation log.  
c. 
Download data from the “Study Companion” tablet. 
d. Dispense from the subject kit the applicable visit treatment box. 
e. 
Affix the tear-off portion of the labels on the product dispensation log. 
f. 
Dispense to the subject the associated non-investigational clinical trial products with 
explanations how and when to use them (only applicable at visit 4 (week 8) and visit 6 
(week 16)). 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 39 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
g. Remind to the subject the importance of complying with the given instructions and 
treatments and to bring back the investigational products together with the “Study 
Companion” tablet at the next visit. 
h. For all female subjects, emphasize the guidelines about contraception and risks in case of 
pregnancy. 
9. Schedule the next follow up visit in: 
 If at visit 3 (week 4): in four weeks ± 3 days 
 If at visit 4 (week 8), visit 6 (week 16) or visit 7 (week 20): in four weeks ± 1 week 
 
 
5.5.4 Visit 5 (week 12) (part I) 
 
1. Question the subject about occurrence of adverse events (AEs) and assess local tolerability (see 
section 7.2). Record occurrence of any events and/or any changes in events that were ongoing at 
the previous clinical trial visit. Document all changes in the eCRF. 
2. Enquire whether any concomitant therapies have been added, stopped, or changed since the 
subject’s last visit. Document all changes in the eCRF. 
3. Conduct a urine pregnancy test (UPT) for female subjects of childbearing potential. 
4. Count atrophic acne scars of each half-face (see section 7.1.1). 
5. Perform an Investigator’s Scar Global Assessment (SGA) of each half-face (see section 7.1.2). 
6. Assess investigator’s preference in terms of overall scar severity (see section 7.1.3); 
7. Count inflammatory, non-inflammatory acne lesions and nodules of each half-face (see section 
7.1.4). 
8. Perform an Investigator’s Global Assessment (IGA) of each half-face (see section 7.1.5). 
9. Assess the skin roughness score of each half-face (see section 7.1.6). 
10. Assess the skin texture change score for each half-face (see section 7.1.7). 
11. For selected sites only (and only if subject and parent/guardian accept through the approved ICF, 
if applicable), take photographs of the face according to the provided procedure. 
12. Provide guidance on the SCARS questionnaire and ask the subject to fill it out for each half-face 
(see Appendix 1). 
13. The product dispenser will: 
a. 
Check the returned investigational products. 
b. Assess subject’s compliance based on the subject’s compliance report available on 
Triacys website and discussion with the subject and report in the eCRF any missing or 
incomplete product application record as indicated in the product dispensation log. 
c. 
Download data from the “Study Companion” tablet. 
d. Dispense from the subject kit the week 12 visit treatment box. 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 40 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
e. 
Affix the tear-off portion of the labels on the product dispensation log. 
f. 
Remind to the subject the importance of complying with the given instructions and 
treatments and to bring back the investigational products together with the “Study 
Companion” tablet at the next visit. 
g. For all female subjects, emphasize the guidelines about contraception and risks in case of 
pregnancy. 
14. Schedule the next follow up visit in four weeks ± 1 week 
 
5.5.5  Visit 8 (week 24) (end of part I, beginning of part II) 
 
1. Question the subject about occurrence of adverse events (AEs) and assess local tolerability (see 
section 7.2). Record occurrence of any events and/or any changes in events that were ongoing at 
the previous clinical trial visit. Document all changes in the eCRF. 
2. Enquire whether any concomitant therapies have been added, stopped, or changed since the 
subject’s last visit. Document all changes in the eCRF. 
3. Conduct a urine pregnancy test (UPT) for female subjects of childbearing potential. 
4. Count atrophic acne scars of each half-face (see section 7.1.1). 
5. Perform an Investigator’s Scar Global Assessment (SGA) of each half-face (see section 7.1.2). 
6. Assess the Investigator’s preference on overall scar severity (see section 7.1.3). 
7. Count inflammatory, non-inflammatory acne lesions and nodules of each half-face (see section 
7.1.4). 
8. Perform an Investigator’s Global Assessment (IGA) of each half-face (see section 7.1.5). 
9. Assess the skin roughness score of each half-face (see section 7.1.6). 
10. Assess the skin texture change score for each half-face (see section 7.1.7). 
11. For selected sites only (and only if subject and parent/guardian accept through the approved 
Informed Consent Form, if applicable), take photographs of the face according to provided 
procedure. 
12. For selected sites only, make skin replica for each half-face (if consent given) (see section 7.1.8). 
13. Provide guidance on the SCARS questionnaire and ask the subject to fill it out for each half-face 
(see Appendix 1). 
14. Provide guidance on the satisfaction questionnaire part I and ask the subject to fill it out (see 
Appendix 2). 
15. For subjects considered to enter part II of the clinical trial, explain the nature and the constraints 
of the part II of the clinical trial to the subjects and to his/her parent(s) or guardian if the subject 
is under the age of 18. 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 41 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
16. If a female subject of childbearing potential agrees to participate in part II of the clinical trial, 
make sure she agrees to continue using the requiring method(s) of contraception. 
17. Ensure the subject (and parent/guardian for subjects under the age of 18) has read, understood, 
dated and signed the approved ICF for part II.  
18. Give a dated and signed copy of the ICF for part II to each subject and parent/guardian if 
applicable. 
19. Fill in the prescription form. 
20. The product dispenser will: 
For all subjects: 
a. 
Check the returned investigational products. 
b. Assess subject’s compliance based on the subject’s compliance report available on 
Triacys website and discussion with the subject and report in the eCRF any missing or 
incomplete product application record as indicated in the product dispensation log. 
c. 
Download data from the “Study Companion” tablet. 
d. Ensure that the subject has returned all used/unused investigational products and the 
“study companion” tablet. All missing investigational product units must be documented 
in the product dispensation log comments section and on other accountability form. 
e. 
For female subjects, reiterate the guidelines about contraception and risks in case of 
pregnancy during 1 month after the end of the trial. 
f. 
Complete the Exit Form Part I in the eCRF and give the reason for clinical trial 
discontinuation (see section 4.4). 
For the subjects continuing into part II: 
g. Dispense 3 bottles of investigational product and the instructions for use. 
h. Affix the tear-off portion of each label on the product dispensation log for part II. 
i. 
Dispense 2 bottles of non-investigational clinical trial products with explanations how 
and when to use them. 
j. 
Remind to the subject the importance of complying with the given instructions and 
treatments and to bring back the investigational products at the next visit. 
k. For all female subjects, emphasize the guidelines about contraception and risks in case of 
pregnancy. 
21. For subjects continuing into part II, schedule the next follow-up visit in 12 weeks ± 2 weeks. 
 
5.5.6 Visit 9 (week 36) (part II) 
1. Question the subject about occurrence of adverse events (AEs) and assess local tolerability (see 
section 7.2). Record occurrence of any events and/or any changes in events that were ongoing at 
the previous clinical trial visit. Document all changes in the eCRF. 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 42 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
2. Inquire whether any concomitant therapies have been added, stopped, or changed since the 
subject’s last visit. Document all changes in the eCRF. 
3. Inquire whether the trial drug regimen has been modified since the last visit. 
4. Conduct a urine pregnancy test (UPT) for female subjects of childbearing potential. 
5. Count atrophic acne scars of each half-face (see section 7.1.1). 
6. Perform an Investigator’s Scar Global Assessment (SGA) of each half-face (see section 7.1.2). 
7. Count inflammatory, non-inflammatory acne lesions and nodules of each half-face (see section 
7.1.4). 
8. Perform an Investigator’s Global Assessment (IGA) of each half-face (see section 7.1.5). 
9. Assess if the subject should continue the treatment for 12 additional weeks on the whole face. 
10. Fill in the prescription form 
11. The product dispenser will: 
a. 
Check the returned investigational products. 
b. Assess subject’s compliance based on an interview with the subject. 
c. 
Dispense 3 bottles of investigational product and the instructions for use. 
d. Affix the tear-off portion of each label on the product dispensation log for part II. 
e. 
Dispense 2 bottles of non-investigational clinical trial products with explanations how 
and when to use them. 
f. 
Remind to the subject the importance of complying with the given instructions and 
treatments and to bring back the investigational products at the next visit. 
g. For all female subjects, emphasize the guidelines about contraception and risks in case of 
pregnancy. 
12. Schedule the next follow up visit in 12 weeks ± 2 weeks. 
 
5.5.7 Visit 10 (week 48) (part II) 
1. Question the subject about occurrence of adverse events (AEs) and assess local tolerability (see 
section 7.2). Record occurrence of any events and/or any changes in events that were ongoing at 
the previous clinical trial visit. Document all changes in the eCRF. 
2. Inquire whether any concomitant therapies have been added, stopped, or changed since the 
subject’s last visit. Document all changes in the eCRF. 
3. Inquire whether the trial drug regimen has been modified since the last visit. 
4. Conduct a urine pregnancy test (UPT) for female subjects of childbearing potential. 
5. Count atrophic acne scars of each half-face (see section 7.1.1). 
6. Perform an Investigator’s Scar Global Assessment (SGA) of each half-face (see section 7.1.2). 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 43 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
7. Count inflammatory, non-inflammatory acne lesions and nodules of each half-face (see section 
7.1.4). 
8. Perform an Investigator’s Global Assessment (IGA) of each half-face (see section 7.1.5). 
9. Assess the skin roughness score of each half-face (see section 7.1.6). 
10. Assess the skin texture change score for each half-face (see section 7.1.7). 
11. For selected sites only (and only if subject and parent/guardian accept through the approved 
Informed Consent Form, if applicable), take photographs of the face according to provided 
procedure. 
12. For selected sites only, make skin replica for each half-face (if consent given) (see section 7.1.8). 
13. Provide guidance on the SCARS questionnaire and ask the subject to fill it out for each half-face 
(see Appendix 1). 
14. Provide guidance on the satisfaction questionnaire part II and ask the subject to fill it out (see 
Appendix 3). 
15. The product dispenser will: 
a. 
Check the returned investigational products. 
b. Assess subject’s compliance based on an interview with the subject. 
c. 
Ensure that the subject has returned all used/unused investigational products. All missing 
investigational product units must be documented in the product dispensation log 
comments section and on other accountability form. 
d. For all female subjects, reiterate the guidelines about contraception and risks in case of 
pregnancy during 1 month after the end of the trial. 
16. Complete the Exit Form for part II in the eCRF and give the reason for clinical trial 
discontinuation (see section 4.4). 
 
5.5.8 Early termination visit 
 
In case of early termination, the procedures corresponding to the next theoretical visit should be 
performed (for instance, if a subject discontinues at week 10, complete the week 12 visit procedures). 
Additional final procedures will be conducted as indicated in the trial flow chart section 5.4. 
 
Note: In case the subject has prematurely discontinued the study during part I, s/he cannot enter part 
II. 
 
 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 44 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
6 
CLINICAL SUPPLIES 
 
Investigational and non-investigational products will be provided by the sponsor and shipped by the 
assigned clinical packager. The investigational products used during this clinical trial are: 
6.1 
INVESTIGATIONAL PRODUCT IDENTIFICATION AND USE 
6.1.1 Product identity 
 
Part I 
 
 
Investigational product 
Investigational comparator 
product 
Trade name 
Tactupump™ Forte  
N/A 
Name of active ingredient 
Adapalene - Benzoyl Peroxide  
N/A (Vehicle Gel) 
Pharmaceutical form 
Gel 
Gel 
Dose or concentration 
Adapalene 0.3% - BPO 2.5% 
N/A 
Formula number 
534.0201 
555.612P 
Total daily dose 
2 pea-sized amounts per half-face 
Mode and frequency of 
administration 
Topical, once daily in the evening 
Location of treated area 
Face 
Manufacturer 
(Name and address) 
G Production Inc. (GPI) 
19400 Route Transcanadienne 
Baie d’Urfé, Québec 
Canada H9X 3S4 
Packaging type and size 
(primary) 
45g airless pump system 
Storage conditions 
Store below 25°C; excursions permitted to 15°-30°C. 
Do not freeze or refrigerate 
 
Part II 
 
Investigational product 
Trade name 
Tactupump™ Forte  
Name of active ingredient 
Adapalene - Benzoyl Peroxide 
Pharmaceutical form 
Gel 
Dose or concentration 
Adapalene 0.3% - BPO 2.5% 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 45 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
 
Investigational product 
Formula number 
534.0201 
Total daily dose 
2 pea-sized amounts per half-face 
Mode and frequency of 
administration 
Topical, once daily in the evening 
Location of treated area 
Face 
Manufacturer 
(Name and address) 
G Production Inc. (GPI) 
19400 Route Transcanadienne 
Baie d’Urfé, Québec 
Canada H9X 3S4 
Packaging type and size 
(primary) 
45g airless pump system 
Storage conditions 
Store below 25°C; excursions permitted to 15°-30°C. 
Do not freeze or refrigerate 
 
6.1.2 Method of treatment assignment 
 
Prior to the start of the clinical trial, a randomization list will be generated by GALDERMA R&D 
and transmitted to the assigned clinical packaging organization for labeling. This randomization is 
used for part I of this clinical trial. The RANUNI routine of the SAS systems will be used for the kit 
number generation to randomly assign the active treatment or the vehicle to the right of left side of 
the face. 
The “left” or “right” side of the face is always defined as the subject’s left or right. 
 
For part I, a subject kit will be composed of 7 boxes containing each 1 pump of  Tactupump™ Forte / 
CD0271 0.3%/CD1579 2.5% Gel and 1 pump of CD0271/CD1579 Vehicle Gel (1 box per 
dispensing visit + 1 extra box). 
 
The kit number indicated on the randomization list will correspond to the kit number indicated on the 
label of the subject kit. 
 
The randomization list will be secured in a locked cabinet and in an electronic file with restricted 
access to only the designated personnel directly responsible for labeling and handling the 
investigational products until the clinical trial database is locked and ready to be unblinded. 
 
At the baseline visit, all eligible subjects will be dispensed a baseline visit box from the subject kit, 
which will be allocated in chronological order of inclusion into the clinical trial, without omitting or 
skipping any number.  


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 46 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
If a number is omitted by mistake, the skipped kit number should be allocated to the next randomized 
subject. 
 
For part II, there will be no subject kit. The sites will receive Tactupump™ Forte / CD0271 
0.3%/CD1579 2.5% Gel bottles in bulk and dispense 3 bottles to the subjects at both week 24 and week 
36 visits (3 bottles for 12 weeks treatment). 
 
6.1.3 Subject Identification Number (SIN) 
 
Each subject will be allocated a unique subject identification number (SIN) at the baseline visit. This 
SIN number will be automatically generated by the eCRF.  
 
During the whole clinical trial, the subject will only be identified using the SIN for all documentation 
and discussion. 
 
6.1.4 Instructions for use and administration 
 
At each product dispensing visit, the product dispenser will give each subject verbal and written 
instructions on how to use the investigational products and non-investigational products. A specific 
focus on risks in case of pregnancy will be made for female subjects.  
 
In addition, at the baseline visit the product dispenser will show the subject how to apply the 
investigational products on each half-face and how to record these applications with the “study 
companion” tablet. This procedure will be thoroughly discussed and reviewed at each trial visit. 
 
Procedure during part I: 
All subjects will apply the investigational products in the evening after washing their face, for 24 
weeks, as described in the instructions for use provided to the subjects. The procedure is as follows: 
1. Check that the “study companion” tablet has enough battery and put it on the provided holder 
2. Wash hands 
3. Wash the entire face using the provided Cetaphil® DermaControl™ Oil Control Foam Wash 
4. Blot dry the face with a soft towel. Do not rub the face. 
5. Take the treatment pump for the RIGHT side of the face (as indicated on the label) and scan 
the QR code with the “study companion” tablet 
6. Follow the instructions given by the “study companion” tablet 
7. Record the application (movie) 
8. Apply a thin film of this treatment on the RIGHT side of the face avoiding eyes, lips and 
mucous membranes. DO NOT SPOT APPLY. Two pea-sized amounts should be enough to 
cover a half of the face. 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 47 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
9. Wash hands 
10. Take the treatment pump for the LEFT side of the face (as indicated on the label) and scan 
the QR code with the “study companion” tablet 
11. Follow the instructions given by the “study companion” tablet 
12. Record the application (movie) 
13. Apply a thin film of this treatment on the LEFT side of the face avoiding eyes, lips and 
mucous membranes. DO NOT SPOT APPLY. Two pea-sized amounts should be enough to 
cover a half of the face. 
 
Procedure during part II: 
All subjects will apply the investigational products in the evening after washing their face, for 24 
weeks, as described in the instructions for use provided to the subjects. The procedure is as follows: 
1. Wash hands 
2. Wash the entire face using the provided Cetaphil® DermaControl™ Oil Control Foam Wash 
3. Blot dry the face with a soft towel. Do not rub the face. 
4. Apply a thin film of the investigational product (Tactupump™ Forte / CD0271 0.3%/CD1579 
2.5% Gel) on the whole face avoiding eyes, lips and mucous membranes. DO NOT SPOT 
APPLY. Four pea-sized amounts should be enough to cover the face. 
5. Wash hands 
 
 
 
 
Investigational product 
Investigational comparator product  
(to be used only during part I) 
Concentration 
Adapalene 0.3% - BPO 2.5% 
N/A 
Dose regimen 
Once daily 
Once daily 
Period of administration 
Evening 
Evening 
Route of administration 
Topical 
Topical 
 
6.1.5 Non-investigational products 
 
In addition, Cetaphil® DermaControl™ Oil Control Foam Wash and Cetaphil® DermaControl™ Oil 
Control Moisturizer SPF 30 will be provided by the sponsor. 
 
Subjects should use Cetaphil® DermaControl™ Oil Control Foam Wash twice daily (once in the 
morning and once in the evening) in order to gently wash their face. Face should thereafter be blotted 
dry with a soft towel. 
Subjects should use Cetaphil® DermaControl™ Oil Control Moisturizer SPF 30 once daily in the 
morning after washing their face, and they may use it as needed during the day (in case of sun 
exposure for instance). 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 48 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
Both products are topical and will be used on the whole face for the whole duration of the trial (up to 
48 weeks). 
 
No specific labels will be used. Subjects will not return these products to the site. No accountability 
will be conducted on these products.  
6.2 
INVESTIGATIONAL PRODUCT PACKAGING AND LABELING 
During part I: 
All investigational products will be supplied in the subject’s kit containing 7 visit boxes labeled with 
an affixed and a tear-off portion.  
 
For treatment documentation, the affixed portion of the label will remain on the appropriate 
packaging. The tear-off portion of the label will be removed at the time of dispensation and attached 
to the corresponding product dispensation log. 
 
The same kit number will be printed on each product container, visit box and subject kit labels. 
 
Treatment identification for emergency purposes will be possible with “unblinding envelopes” or 
equivalent, stating the treatment number, investigational product identification, batch number and 
investigational product expiration date, as applicable. 
 
During part II: 
The subjects will receive 3 bottles of investigational products (enough supply for 12 weeks 
treatment). These bottles will be labeled with an affixed and a tear-off portion. For treatment 
documentation, the affixed portion of the label will remain on the appropriate packaging. The tear-
off portion of the label will be removed at the time of dispensation and attached to the corresponding 
product dispensation log. 
 
 
If more than one batch is used with different expiration dates, in order to maintain blinding, only one 
expiry date, the most conservative, will be listed on the container label as well as on the «scratch-
off» field if applicable. 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 49 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
6.3 
INVESTIGATIONAL PRODUCT MANAGEMENT 
6.3.1 Accountability 
 
Upon receipt of the clinical supplies at the site, the product dispenser will conduct a complete 
inventory of all investigational products and assume responsibility for their storage, accountability 
and dispensation. 
The investigator or designee will sign the original “Receipt of Clinical Supplies” Form (or any 
acknowledgment of receipt) upon receipt and inspection of the supplies, fax the signed copy to 
GALDERMA R&D or designated contractor and retain the receipt in the Investigator Site File (ISF). 
All supplies sent to the investigator site will be accounted for and in no case used in any 
unauthorized situation.  
 
All used and unused investigational product will be appropriately inventoried by GALDERMA R&D 
/CRO representative and returned to Galderma R&D /designated contractor for further reconciliation 
and destruction. 
 
6.3.2 Dispensing 
 
All investigational and non-investigational products will be provided only to subjects enrolled into 
the clinical trial, at no cost and in accordance with the conditions specified in the protocol. 
 
Dispensation will be appropriately documented on the appropriate product dispensation log by the 
product dispenser at each visit. 
 
It is important that no subject runs out of clinical trial supplies between visits.  
 
The product dispenser will follow the accurate prescription according to the allocated kit (applicable 
during part I only). 
 
During part I, each subject will receive a new visit box containing one pump of each investigational 
product at baseline and each post-baseline visit except at week 1 and week 24.   
During part II, each subject will receive 3 bottles of Tactupump™ Forte / CD0271 0.3%/CD1579 
2.5% gel at the week 24 and week 36 visits. 
 
During part I, all efforts will be taken to keep the evaluator (investigator or designee) blinded by 
restricting his/her contact with the investigational products. 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 50 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
The product dispenser must be different from the clinical trial efficacy and safety evaluator in order 
to maintain the blind during part I (see section 6.5). 
 
During part I, treatment kits will be dispensed in ascending sequential order according to the 
chronological order of enrolment of subjects into the clinical trial. 
 
6.3.3 Investigational product compliance management and record 
 
Each subject will be instructed by the product dispenser about the importance of being compliant 
with the investigational products throughout the clinical trial as well as the importance of returning 
the products (used and/or not used) at the follow-up visits (except at week 1). 
 
The investigational products will be collected, counted and documented on the product dispensation 
log or other accountability document as applicable, at all post-baseline visits (except week 1), by the 
product dispenser. 
 
During part I of this trial, subjects will receive a tablet called “study companion”, developed by 
Triacys. This tablet will guide them through the product application. The objective is to optimize 
product compliance and avoid applications on the wrong side of the face. 
 
The product compliance will be assessed using this tablet via daily recording of product applications 
by the subject. A GPRS card is inserted into this tablet and real-time logs will be sent automatically 
without any action required from the subject and made available on a website. This will allow 
monitoring of the use of the tablet by the subjects by Triacys, Galderma R&D/representative and/or 
the site personnel. At each visit, the product dispenser will review the data available on this website 
for the subject. In case of missing or incomplete product application records, the product dispenser 
will impute the missing data in the eCRF after discussion with the subject. At the end of the trial, 
compliance will be calculated using both data retrieved from the tablet and data in the eCRF.  
 
In addition, videos of product applications will be made every day by the subjects with this “study 
companion” tablet. At the end of the trial, these videos will be analyzed by qualified operators in 
order to verify that the subject has applied the correct product on the correct side. At each visit, the 
subject will return the tablet and videos will be downloaded on a site’s computer by the product 
dispenser (as data back-up) via a specific application. At the end of the trial, once the videos will 
have been analyzed and the compliance report will have been finalized, they will be destroyed. This 
compliance report will be archived at the sites as a transcription of the videos. In no case, personnel 
other than the qualified operators will have access to the videos. 
 
During part II of this trial, the “study companion” tablet will not be used. The compliance of the 
subject will be documented in the product dispensation log based on the discussion between the 
product dispenser and the subject. 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 51 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
 
During the data review meetings (one after part I and one after part II), investigational product 
compliance for all subjects will be determined and reviewed by the sponsor’s clinical team for 
possible exclusion from the Per Protocol (PP) population. 
 
6.3.4 Storage of investigational product 
 
The investigator has to agree to keep all investigational products in a safe, temperature controlled 
and secure area with restricted access, in accordance with applicable regulatory requirements (e.g., in 
the site pharmacy, if applicable). 
 
Investigational products should be stored at appropriate storage conditions specified by 
GALDERMA R&D (see section 6.1.1). Temperature should be monitored on every working day.  
 
6.3.5 Return of investigational product 
 
The product dispenser will inform each subject about the importance of returning the investigational 
products (used and/or not used) at each trial visit (except week 1 visit). 
In the event of early termination/suspension of the clinical trial for safety reasons, a rapid recall of 
the trial products will be initiated.  The investigator or designee must immediately instruct all 
subjects to stop the clinical trial treatment regimen and return the products to the clinical trial site. 
As a general procedure, GALDERMA R&D will provide the investigator with a detailed list of units 
being recalled so that any of the units remaining on site can be put immediately into quarantine. 
6.4 
DOSE MODIFICATION 
Local cutaneous reactions including erythema, scaling, dryness, and stinging/burning may be 
experienced with use of Adapalene 0.3% - BPO 2.5% gel.  All these adverse reactions are easily 
managed depending upon the severity of these adverse reactions. 
Patients should be instructed to use a moisturizer (if possible the one provided for this trial) and if 
needed, investigators may reduce temporarily the frequency of the application of Adapalene 0.3% - 
BPO 2.5% gel (eg. every other day), or temporarily discontinue use. In such cases, the treatment on 
both half-face should be suspended, even if the irritation is only on one half-face. 
These are most likely to occur during the first four weeks of treatment but are mostly mild to 
moderate in intensity, and usually improve with continued use of the medication. 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 52 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
All dose modifications will be documented in the subject’s source data and reported in the eCRF 
(treatment compliance page).  
In addition, for part II, at visits Week 36 and Week 48, any dose modification for safety reasons 
should lead to the collection of additional information (date of onset and resolution, diagnosis, 
severity, seriousness and treatment(s) if any). The Sponsor should be notified by email 
(pharmacovigilance@galderma.com) within 24 hours after being informed of this dose modification 
for safety reasons. 
 
6.5 
BLINDING 
6.5.1 Verification of blinding 
 
The clinical trial design is considered investigator-blind during part I based on the following 
rationale: 
1. 
Both trial products will be filled in the same type of packaging material and there will be no 
sign that could indicate which one is the active product and which one is the vehicle. 
2. 
The investigational products will be dispensed by someone other than the evaluator 
(investigator or designee) designated as the product dispenser in order to maintain the blind. 
3. 
Additionally, both the product dispenser and the subject will be instructed not to discuss the 
investigational products with the evaluator (investigator or designee) 
4. 
The product dispenser and the investigator will not have access to the unblinded randomization 
list.  
 
These above-mentioned procedures will be followed to ensure the integrity of the blinding of the 
clinical trial. 
 
Part II is open-label. 
 
6.5.2 Clinical trial unblinding 
6.5.2.1 Unblinding during the clinical trial (for part I) 
 
At the investigational sites, unblinding forms or equivalent with the identification of the side of the 
face assigned to one of the investigational products for an individual subject will be made available 
and may be used in medical emergencies for therapeutic reasons to reveal treatments assigned. 
In such a medical emergency, the investigator will break the blind only for the subject involved.  
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 53 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
The investigator must notify the sponsor immediately in the event of such an emergency (see contact 
details in Section 8.4).  If possible, the investigator should notify the sponsor before breaking the 
blind in order to discuss this decision with the sponsor.  The investigator is required to document 
each case of emergency unblinding on the appropriate form (provided by the sponsor) and fax the 
completed form to the sponsor immediately. Original will be filed in the subject’s file. 
Note: GALDERMA Clinical Safety department will also have a set of unblinding forms or 
equivalent. 
 
6.5.2.2 Unblinding at the end of part I of the clinical trial 
 
In general, unblinding will occur after the completion of the following steps: 
 
 
1. All clinical trial data for part I from the eCRF, “study companion’ data, weighing of returned 
products if necessary, have been entered into the database 
2. All data queries, if any, have been resolved.  
3. Major deviations or intercurrent events, if any, have been previously defined and identified, i.e. 
safety and efficacy evaluability have been determined for each subject 
4. All coding for adverse events and therapies have been approved and SAE/Pregnancy reconciliation 
has been completed 
5. Data management has integrated the above evaluability information into the database 
6. The statistical analysis plan (SAP) has been finalized 
7. The database has been formally validated and locked 
 
Written approval from data management, statistician and clinical project manager will be required 
for unblinding the clinical trial. 
 
Part II is open-label. 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 54 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
7 
EFFICACY AND SAFETY ASSESSMENT 
7.1 
EFFICACY ASSESSMENTS 
 
Clinical evaluations should be performed by the same evaluator (investigator or designee) throughout 
the clinical trial.  
 
If it is not possible to use the same evaluator to follow a subject, then evaluations should overlap for 
at least one visit in order to examine the subject together and discuss findings and this should be 
documented in the source documents. At least for the baseline assessments and the final assessments 
of part I (week 24/early termination), the evaluator should be the same person. 
 
The evaluated areas must be examined under the same conditions of light exposure at each visit 
(same angle to avoid shadow and same light source, i.e. artificial or daylight). 
 
Both during part I and part II, the zone in the middle of the face (approximately 2 cm large and the 
nose) will be excluded for the clinical efficacy evaluations because subjects may apply a mix of both 
investigational products (active and vehicle) on this zone. See figure below. 
 
 
7.1.1 Atrophic acne scar count 
 
Each type of atrophic acne scars will be counted separately for each half-face at each trial visit. The 
scars will be counted according to their size defined in 2 categories (Jacob, et al., 2001) using 2- and 
4-mm punch biopsy tools for size classification: 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 55 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
 Atrophic scars 2-4 mm: includes boxcar (sheer edges), rolling (irregular surface), and undetermined 
types 
 Atrophic scars > 4 mm: includes boxcar (sheer edges), rolling (irregular surface), and undetermined 
types. 
The evaluator will count both types of atrophic scars for each region:  left and right forehead, left and 
right cheeks, and left and right side of the chin above the jaw line (see figure above).  
 
On each half-face, the scar counts will be added together to obtain the total number of scars per half-
face.  
 
7.1.2 Investigator’s scar global assessment (SGA)  
 
The evaluator will assess the severity of atrophic acne scars of each half-face at each trial visit, 
performing a static (“snapshot”) evaluation of the severity based on the scale below. 
The evaluator should make no reference to baseline or other previous visit when evaluating each 
subject’s half face. 
Table 1: Investigator’s Scar Global Assessment (SGA) 
Category 
Score Description 
Clear 
0 
No visible scars from acne 
Almost Clear 
1 
Hardly visible scars from 50 cm away 
Mild 
2 
Easily recognizable ; less than half the affected face area* involved 
Moderate 
3 
More than half and less than 75% of the affected face area* involved 
Severe 
4 
More than 75% of the affected face area* affected  
* The affected face area corresponds to a half-face. 
 
7.1.3 Investigator’s preference in terms of overall scar severity 
 
At week 12, week 24 and in case of early termination (during part I only), the evaluator will assess 
his/her preference in terms of overall acne scars severity between the two half faces: 
 
Table 2: Investigator’s preference in terms of overall scar severity 
Overall efficacy 
(in terms of acne scars) 
Left a lot 
better 
than right 
Left a little 
bit better 
than right 
 
No 
preference 
Right a little bit 
better 
than left 
Right a lot 
better 
than left 
Score 
-2 
-1 
0 
1 
2 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 56 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
7.1.4 Acne lesion count 
 
Each type of lesion will be counted separately for each half-face at each trial visit. The evaluator 
will take the lesion counts from left and right forehead, left and right cheeks, and left and right side 
of the chin above the jaw line (see figure above).  
 
For each half-face, the lesion counts will be added together to obtain a Total Lesion count per half-
face. The following are the definitions of the lesions that will be counted. 
 
Non-inflammatory lesions 
Open Comedone - A mass of sebaceous material that is impacted behind an open follicular orifice 
(blackhead). 
Closed Comedone - A mass of sebaceous material that is impacted behind a closed follicular orifice 
(white head). 
 
Inflammatory lesions 
Papules - A small, solid elevation less than one centimeter in diameter. Most of the lesion is above 
the surface of the skin. 
Pustules - A small, circumscribed elevation of the skin which contains yellow-white exudates. 
 
Other lesions 
Nodules - A circumscribed, elevated, solid lesion generally more than 1.0 cm in diameter with 
palpable depth. 
 
7.1.5 Investigator’s global assessment of acne severity (IGA) 
 
For the inclusion criterion (subjects should have an IGA of 3 or 4), the evaluator will assess the 
severity of acne for the whole face of the subject using the scale described in Table 3 below. 
 
For all other IGA assessments (at baseline and at each post-baseline visit), the evaluator will assess 
the severity of acne for each half-face using the scale described in Table 3 and adapted for half-
faces. The evaluator will evaluate the subject’s acne at each visit performing a static (“snapshot”) 
evaluation of acne severity. The evaluator should make no reference to baseline or other previous 
visit when evaluating the subject’s acne. 
 
The global severity assessment is outlined in the following table (IGA): 
 
 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 57 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
Table 3: Investigator’s global assessment of acne (IGA) 
Category 
Score 
Description 
Clear 
0 
Clear skin with no inflammatory or non-inflammatory 
lesions 
Almost Clear 
1 
A few scattered comedones and a few small papules 
Mild 
2 
Easily recognizable; less than half the face is involved. 
Some comedones and some papules and pustules. 
Moderate 
3 
More than half of the face is involved. Many comedones, 
papules and pustules. One small nodule may be present. 
Severe 
4 
Entire face is involved. Covered with comedones, 
numerous papules and pustules. Few nodules may or may 
not be present. 
 
7.1.6 Investigator’s assessment of the skin roughness 
 
The evaluator will evaluate skin roughness for each half-face at baseline, week 12, week 24, week 
48 and in case of early termination by using the five-point scale below: 
 
Table 4: Skin roughness score 
Category 
Score 
Description 
None 
0 
Very smooth 
Minimal 
1 
Smooth 
Mild 
2 
Somewhat smooth  
Moderate 
3 
Slightly rough  
Severe 
4 
Very rough  
 
7.1.7 Investigator’s assessment of the skin texture change 
 
Overall facial skin texture change will be graded by the evaluator for each half-face at week 12, 
week 24, week 48 and in case of early termination as follows:  
 
 
 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 58 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
Table 5: Skin texture change score 
Score 
Description 
0 
Worse 
1 
No change 
2 
1-25% = slight improvement 
3 
26-50% = moderate improvement 
4 
51-75% = marked improvement 
5 
76-90% = almost complete improvement 
6 
91-100% = complete improvement 
 
7.1.8 Quantitative evaluation of skin microrelief (skin replica) 
 
At baseline, week 24, week 48 and early termination (in case it occurs after week 8), skin replicas 
will be performed on each cheek (size 5x2 cm) by using specific silicon (Silflo®) and by following 
the provided detailed procedure. The 5x2 cm region should be chosen - whenever possible - where 
there are the least scarring and should be equivalent on both sides.  
The skin replica will be analyzed for skin microrelief using fringe projection. Roughness parameters 
will be calculated for the whole replica and on the regions of the replica without any lesion. 
This will be performed at one selected site only and if the subject has given consent for this 
procedure. 
 
7.2 
SAFETY ASSESSMENTS 
A safety assessment will be conducted for all subjects at the baseline visit (after the ICF has been 
signed) and every subsequent visit. The safety parameters include adverse events (AEs) and 
assessment of local tolerability. 
 
7.2.1 Local tolerability assessment 
Signs and symptoms of local cutaneous irritation (erythema, scaling, dryness and/or stinging/ 
burning) are possible during treatment with Adapalene 0.3% - BPO 2.5%. 
 
The investigator will evaluate erythema, scaling, dryness and/or stinging/burning at each trial visit. 
The investigator will record stinging/burning after discussion with the subject regarding the previous 
application days. The investigator will ask an open-ended question, taking care not to influence the 
subject’s answer, such as: “Have you experienced any sensations immediately following products 
application (within 5 minutes)?” 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 59 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
Erythema, scaling, dryness, and stinging/burning will be graded at baseline and each post- 
baseline visit as follows (to be done for each half-face): 
 
 
 Erythema: abnormal redness of the skin 
None  
0: No erythema 
Mild 
 
1: Slight pinkness present 
Moderate 
2: Definite redness, easily recognized 
Severe  
3: Intense redness 
 
 Scaling: abnormal shedding of the stratum corneum 
None  
0: No scaling 
Mild 
 
1: Barely perceptible shedding, noticeable only on light scratching or rubbing 
Moderate 
2: Obvious but not profuse shedding 
Severe  
3: Heavy scale production 
 
 Dryness: brittle and/or tight sensation. 
None   
0: No dryness 
Mild   
1: Slight but definite roughness 
Moderate  
2: Moderate roughness 
Severe  
3: Marked roughness 
 
 Stinging/Burning: prickling pain sensation immediately after application (within 5 minutes). 
None   
0: No stinging/burning 
Mild   
1: Slight warm, tingling/stinging sensation; not really bothersome 
Moderate  
2: Definite warm, tingling/stinging sensation that is somewhat bothersome 
Severe  
3: Hot, tingling/stinging sensation that has caused definite discomfort 
 
Note: Stinging/Burning at the baseline visit should be assessed as none (0). 
 
An Adverse Event will be recorded if the severity of the signs and symptoms is such that: 
 The subject’s participation in the trial is interrupted at his/her request or at the investigator’s 
request after the week 4 visit  
 The subject permanently discontinues the treatment at his/her request or at the investigator’s 
request. 
 The subject requires concomitant prescription or OTC therapy (other than moisturizers). 
Note: Need for increased moisturizer use does NOT constitute an AE. 
 
Any new sign or symptom, which is not included in the scheduled evaluation of tolerability, 
should be recorded as an Adverse Event, including those of mild intensity. 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 60 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
7.2.2 Adverse events 
Adverse events (AEs) are to be monitored throughout the course of the clinical trial.  All AEs are to 
be reported on the Adverse Event Form of the eCRF with complete information as required.  If AEs 
occur, the main concern will be the safety of the subjects.  At the time of the ICF signature, each 
subject must be provided with the name and phone number of clinical trial site personnel for 
reporting AEs and medical emergencies. 
 
7.3 
PATIENT RELATED OUTCOMES 
The following Patient Reported Outcome (PRO) questionnaires should be filled out by the subjects. 
The investigator or delegate should check all questions of the PRO questionnaires for completeness 
prior to the subject leaving the office. 
 
7.3.1 Questionnaire on acne scar appearance 
 
Subject will assess acne scar appearance of each half-face at baseline, week 12, week 24, week 48 
and in case of early termination using the SCARS questionnaire (Self-assessment of Clinical Acne 
Related Scars) provided in Appendix 1. 
 
7.3.2 Subject satisfaction questionnaire  
 
At week 24/early termination (in case of early termination during part I), subjects will complete the 
part I satisfaction questionnaire regarding the treatments and non-investigational products they have 
been using in this trial (see Appendix 2). 
 
At week 48/early termination (in case of early termination during part II), subjects will complete a 
satisfaction questionnaire regarding the non-investigational products they have been using in this 
trial (see Appendix 3). 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 61 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
7.4 
OTHERS 
7.4.1 Photographs 
 
Standardized digital photographs of the whole face (front, right and left) will be taken using a 
Canfield Scientific stereostatic device (Visia CR®) and/or a 3D camera (for instance, 3D Lifeviz™). 
Detailed procedures will be provided.  
Photographs will be taken at baseline, week 12, week 24 and week 48. 
This will be performed at selected sites only and if the subject has given consent for this procedure. 
7.5 
APPROPRIATENESS OF MEASUREMENTS 
Efficacy is evaluated by assessing the number of inflammatory and non-inflammatory lesions as well 
as a global assessment of acne severity by the investigator (IGA) which are current and non-invasive 
techniques for assessing acne severity.  
 
In addition, as this is the main trial objective, atrophic acne scars will also be counted and 
investigators will make an overall assessment of scars severity (SGA) as it has been previously done 
in a previous trial (protocol RD.03.SPR.40183E). They will also evaluate the side they prefer in 
terms of acne scars. These techniques are non-invasive. 
 
Furthermore investigators will assess the skin roughness and the skin texture change using discrete 
scores. These are non-invasive exploratory assessments. At one selected site, skin replica will be 
performed to get a quantitative assessment of skin microrelief. This technique is very minimally 
invasive (silicon imprint of the skin) and has been used in previous trials in a similar subject’s 
population (e.g. RD.03.SPR.29088). These assessments are classified as exploratory efficacy 
assessments as a possible effect of Adapalene on cosmetic outcomes as shown in subjects with 
photodamaged skin is hypothesized in younger subjects (Kang, et al., 2003).  
Safety will be assessed through the reporting of adverse events and local tolerability assessment on 
an ongoing basis as a well-established process in clinical trials. 
 
Impact of trial treatments on subjects’ assessment of their scars appearance will be assessed using the 
SCARS questionnaire which has been developed by the Global Alliance to Improve Outcomes in 
Acne following the recommendations given by FDA guidance for developing patient reported 
outcome tools with patient interviews (Paper submitted in December 2015). This is the first time this 
questionnaire is used in a clinical trial but it was designed to be suitable for self-completion and to be 
rapidly completed (2-5 min) within a clinical research setting. This questionnaire was adapted to a 
split-face design. 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 62 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
To collect specifically the subject’s feed-back on the treatments and on the associated cosmetics 
products used in the trial, a subject satisfaction questionnaire will be used. 
 
8 
ADVERSE EVENTS 
 
Throughout the course of the clinical trial, all adverse events will be monitored and reported on an 
Adverse Event Form of the eCRF disclosing any requested and known information. When adverse 
events occur, the main concern is the safety of the clinical trial subjects. At the time of the ICF 
signature, each subject will be given the name and telephone number of clinical trial site personnel to 
whom AEs and medical emergencies should be reported. 
8.1 
DEFINITIONS 
8.1.1 Adverse Events (AE) 
 
According to ICH E2A, an AE is any untoward medical occurrence in a subject or clinical 
investigation subject administered a pharmaceutical product and which does not necessarily have a 
causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory value), symptom, or disease temporally associated with the use of 
a medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product. 
Thus any new sign, symptom or disease, or clinically significant increase in the intensity of an 
existing sign, symptom or disease since the first visit (including the disease being treated), should be 
considered as an adverse event. Lack of efficacy should not be considered as an AE. 
 
Each new episode of a chronic disease (e.g., hay fever, allergy, etc.) should be reported as a new 
AE. 
 
Notes: 
- 
A diagnosis should preferably be reported rather than the signs, symptoms or abnormal 
laboratory values associated with the report of an AE.  However, a diagnosis should be reported 
only if, in the investigator’s judgment, it is relatively certain.  Otherwise, symptoms, signs, or 
laboratory values should be used to describe the AE. 
- 
Any new sign or symptom appearing after accidental or intentional overdose or misuse should 
also be reported as an adverse event. 
- 
Pregnancy should not be considered as an adverse event but must be followed up as described in 
section 8.5. 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 63 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
There may be side effects during treatment with the investigational products, as described in the 
product monograph for Tactupump™ Forte and in this protocol (mild to moderate application site 
reactions, such as skin irritation characterized by scaling, dryness, erythema, and burning/stinging). 
The course of these expected events will be assessed and reported on the Local Tolerability 
Assessment Forms.  An Adverse Event Form will be completed only if the severity of the expected 
signs and symptoms is such that an interruption/discontinuation of the subject’s participation in the 
clinical trial, at his/her request or at the investigator’s, occurred and/or if a concomitant medication is 
prescribed to treat the sign/symptom(s). 
 
8.1.2 Serious Adverse Events (SAE) 
 
A serious adverse event is any untoward medical occurrence that at any dose:  
 results in death, 
 is life-threatening, 
 requires hospitalization or prolongation of existing hospitalization, 
 results in persistent or significant disability/incapacity, or 
 is a congenital anomaly/birth defect. 
Important medical events that may not result in death, be life-threatening, or require hospitalization 
may be considered an SAE when, based upon appropriate medical judgment, they may jeopardize the 
safety of the subject, and may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition. Examples of such events are intensive treatment in an emergency 
room or at home for allergic bronchospasm, blood dyscrasia, or convulsions that do not result in 
hospitalization. 
Note: 
- 
The term “life-threatening” 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 was 
more severe. 
 
- 
Hospitalization is considered to have occurred if the subject has had to stay in hospital overnight. 
The criterion for the prolongation of hospitalization is also defined as an extra night in hospital. 
Hospitalization solely for the purpose of diagnostic tests, even if related to an adverse event, 
elective hospitalization for an intervention which was already planned before the inclusion of the 
subject in the clinical trial, admission to a day-care facility, social admission (e.g. if the subject 
has no place to sleep), or administrative admission (e.g. for a yearly examination) may not 
themselves constitute sufficient grounds to be considered as a serious adverse event. 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 64 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
8.1.3 Unexpected adverse drug reaction 
 
According to ICH E6, an unexpected adverse drug reaction is defined as an adverse reaction, the 
nature or severity of which is not consistent with the applicable trial drug information (in this clinical 
trial: the approved Canadian product monograph at the time of AE occurrence). 
 
8.1.4 Adverse event reporting period 
 
All AEs occurring during the clinical trial period from when the subject signs the Informed Consent 
Form to the end of the subject’s participation will be reported. 
The sponsor should be informed if the investigator becomes aware of any unusual safety information 
or any safety information that appears to be drug-related involving a subject who has participated in 
a clinical trial, even after a subject has completed the clinical trial. The investigator should be 
diligent in looking for possible latent safety effects that do not appear until after the medication has 
been discontinued. 
 
8.1.5 Severity 
 
Severity is the clinical determination of the intensity of an adverse event and not of a disease. 
 
The investigator will classify the intensity of AEs using the following definitions. For this 
classification, the investigator will take into account the possible range of the intensity of the event 
and report the grade of intensity which is the most appropriate according to his/her medical 
judgment. 
Mild 
Awareness of sign or symptom, but easily tolerated 
 
Moderate 
Discomfort, enough to cause interference with usual activity 
 
Severe 
Incapacitating with inability to work or perform usual activity 
 
 
 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 65 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
8.1.6 Relationship to the investigational product 
 
The investigator has to determine whether or not there is a reasonable causal relationship between 
the investigational product and the AE. Medical judgment should be used to determine the 
relationship, considering all relevant factors, including pattern of reaction, temporal relationship, 
positive dechallenge or rechallenge, relevant medical history, and confounding factors such as co-
medication or co-concurrent diseases. 
 
The expression “reasonable causal relationship” is meant to convey in general that there are facts or 
arguments to suggest a causal relationship (International Conference on Harmonization (ICH) E2A, 
section IIIA 1). 
 
The relationship assessment for an adverse event will be completed using the following definitions as 
a guideline for all adverse events occurring during this clinical trial: 
 
Reasonable possibility: 
According to the reporting investigator, there is a reasonable possibility (i.e., suggestive evidence or 
arguments) that there is a causal relationship irrespective of the dose administered between: 
 The trial product (investigational product, active comparator, or placebo/vehicle, etc.) and the 
AE,  
 The clinical trial protocol procedure (e.g.  UV-induction, biopsy, xylocaine injection, blood test 
or intraocular pressure measurement, etc.) and the AE. 
 
No Reasonable Possibility: 
No suggestive evidence or arguments can be identified regarding a causal relationship between the 
investigational product or the clinical trial protocol procedure and the AE. 
8.2 
PROCEDURES FOR REPORTING ADVERSE EVENTS 
Adverse events will be collected from the time that a subject signs the ICF to his/her final trial visit. 
 
At each visit, the investigator (or sub-investigator) will enquire about adverse events using an open 
question taking care not to influence the subject’s answer (e.g., “Have you noticed any change in 
your health since the last visit?”). Direct questioning and examination will then be performed as 
appropriate. 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 66 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
Any AE occurring during the AE reporting period, whether it is related to the investigational product 
or not, will be recorded immediately in the source document, and described in the Adverse Event 
Form of the eCRF along with the date of onset, severity, relationship to the investigational products, 
and outcome, without omitting any requested and known information.  Additional information may 
be requested under certain circumstances.  Adverse Events assessed as related to the treatments will 
be monitored until they are completely or satisfactorily resolved. Other AEs will be monitored until 
the last visit if they are not resolved or satisfactorily resolved. 
The investigator will obtain and maintain in the subject’s files all pertinent medical records, 
information and medical judgment from colleagues who assisted in the treatment and follow-up of 
the subject. If necessary, the investigator will contact the subject’s personal physician or hospital 
staff to obtain further details. 
When an AE related to the treatment persists at the end of the clinical trial, the investigator will 
ensure the subject is followed up until the investigator and GALDERMA R&D agree that the event 
is satisfactorily resolved. 
8.3 
PROCEDURE FOR SUSPECTED ALLERGIC CONTACT REACTION 
This is a general procedure and further details can be discussed with the sponsor. 
 Stop the trial product. 
 Take a picture of the affected area and the non-affected surrounding skin 
 Document the event and report it immediately to the sponsor  within 24 hours of receipt of 
the information as described in section ‎8.4. 
 
8.3.1 In case of suspicion of allergic contact dermatitis  
1. After all signs and symptoms have resolved and after a minimum of two weeks from last 
treatment application, perform a re-challenge test with the assigned trial product.  
2. Ensure the subject has not been receiving any treatment with corticosteroids or antihistamines 
of any route of administration the week before testing. 
3. Ensure that the skin on the back has not been exposed to the sun or artificial ultraviolet 
sources the week before testing. 
4. Apply an appropriate quantity of the assigned trial product to fill the cupule of the test 
chamber on the skin of the upper back on either the right or left side of the centre line (or the 
inner forearm if the back cannot be tested). If no test chamber is available on-site, patch test 
units will be provided. It may be preferable to perform the test under semi-occlusive 
conditions depending on the irritant potential of the trial product and the intensity of the 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 67 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
reaction that was observed. The method to be used should be discussed with the sponsor. 
Choose a skin site that was not previously involved in the inflammatory skin reaction. Cover 
it for 48 hours with a hypoallergenic tape. 
5. The subject should be informed about avoiding exercise, showers, application of toiletries, 
etc. to keep the test system dry 
6. After 48 hours, remove the tests and evaluate the site: 
 at approximately 30 minutes after patch test removal (1st reading) and, 
 24 to 48 hours later (i.e. 72 or 96 hours after application) (2nd reading). 
 A facultative 3rd reading may be performed 96 to 120 hours later (i.e. 6 to 7 days after 
application of the patch) if the overall assessment was equivocal or if requested by the 
sponsor. 
 Pictures of the tested areas will be taken systematically at each reading and properly 
documented. 
 
Duration of 
trial product 
application 
1st Reading 
2nd  Reading 
3rd reading  
(optional) 
48 hours 
48 hours after trial product 
application (30 minutes 
after patch test removal) 
 72 to 96 hours after 
trial product application 
(24 to  48  hours after 
patch test removal) 
6 or 7 days after trial 
product application (96 to 
120 hours after patch 
removal) 
  
7. Refer to the scoring system used by the International Contact Dermatitis Research Group 
(ICDRG) to assign a score at each reading (Spiewak, 2008):  
Score Morphology 
Interpretation 
- 
No skin changes in the tested area 
Negative 
? 
Faint, non-palpable erythema  
Doubtful reaction 
+ 
Palpable erythema (moderate edema or 
infiltrate), papules not present or scarce, 
vesicles not present  
Weak positive reaction 
++ 
Strong infiltrate, numerous papules, vesicles 
present 
Strong positive reaction 
+++ 
Erythema, infiltration, confluent vesicles, 
bullae or ulceration 
Extreme positive reaction 
 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 68 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
ir 
Inflammation sharply limited to the exposed 
area, lack of infiltrate, small petechiae, 
pustules, and efflorescences other than 
papules and vesicles 
Irritant reaction 
Nt 
 
Not tested 
 
8. At last reading, provide an assessment regarding a possible sensitization reaction using 
the following scale: 
Sensitization Reaction 
0 Negative (absence of reaction or might be irritant reaction) 
1 Equivocal 
2 Positive 
 
9. Report the results from the re-challenge test as directed by the sponsor and document 
with photographs. 
10. In case of absence of reaction, the subject may resume treatment if appropriate 
11. If the re-challenge is positive or equivocal, notify the sponsor immediately. Except in 
specific situations, a new series of patch test will be initiated as directed by the sponsor 
(with individual ingredients at different concentrations if applicable, and possibly 
negative and positive controls) after a minimum of additional two weeks (but not later 
than 6 months) and after all signs and symptoms have resolved. The patch tests will be 
placed on the subject’s back (or the inner forearm if the back cannot be tested) distant 
from the site of the re-challenge test (e.g., the left upper back skin if the re-challenge test 
was done on the right side). Follow the same procedure for the patch test as for the re-
challenge.  
 
8.3.2 In case of suspicion of immediate contact skin reaction (such as urticaria) 
 
A case by case approach will be applied and the procedure to follow will be discussed with the 
sponsor. 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 69 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
8.4 
PROCEDURE FOR REPORTING A SERIOUS ADVERSE EVENT 
For any serious adverse event occurring during the clinical trial period, whether or not related to the 
treatment, expected or not, the investigator will: 
 
1. Take prompt and appropriate medical action, if necessary. The safety of the subject is the 
main priority. 
2. Immediately (no later than 24 hours) inform the sponsor of the event by fax/email, and 
discuss further steps to be taken: 
 
 
GALDERMA R&D  
Name 
Title 
 
) 
Address 
 
 
 
Tel. during office hours 
 
Tel. Outside office hours 
 
Fax  
 
Email 
pharmacovigilance@galderma.com 
 
The treatment allocation may be unblinded for the particular subject under either one or both of the 
following circumstances: 
- 
If knowledge of the trial treatment is medically necessary in order to manage subject’s 
safety, 
- 
If GALDERMA pharmacovigilance decides that the event requires expedited reporting to 
the Regulatory Authorities and to the IRBs/ECs, whereby knowledge of the treatment 
allocation is necessary. 
3. Complete the SAE Form provided by the CRA (Clinical Research Associate) at the start of the 
clinical trial (it is also available in the eCRF system as pdf document). Fax or send by email the 
completed form, accompanied by any other relevant information or anonymized medical records 
(e.g., laboratory test results) within 24 hours to the sponsor (see contact details above). The 
demographics, medical history, previous and concomitant therapies, and adverse event pages of 
the eCRF must be completed and available for review in the EDC system at the time of the 
report. 
4. Monitor and record the progress of the event until it resolves or reaches a clinically stable 
outcome, with or without sequel. For all additional follow-up evaluations, fax or send by e-mail 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 70 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
all additional follow-up information on the SAE to the sponsor (see contact details above) within 
24 hours of receipt of the updated information.  SAEs will be monitored until the investigator and 
sponsor agree that the event is satisfactorily resolved. 
5. Obtain and maintain in his/her files all pertinent medical records, information, and medical 
judgments from colleagues who assisted in the treatment and follow-up of the subject. If 
necessary, contact the subject’s personal physician or hospital staff to obtain further details. 
6. Inform GALDERMA R&D of the final outcome of the event. Send a revised or updated SAE 
Form, if appropriate (usually required every ten days) to the sponsor. 
7. Comply with the applicable regulatory requirements related to the reporting of SAEs to 
IRB/EC. 
 
8.5 
PROCEDURES FOR REPORTING PREGNANCIES 
Any pregnancy occurring during clinical trials, where the foetus could have been exposed to the 
investigational products, must be followed-up until outcome in order to ensure the complete 
collection of safety data on GALDERMA R&D product. 
 
In the case of a pregnancy of a clinical trial subject, the investigator will: 
1. Withdraw the subject from the clinical trial and complete all appropriate visit evaluations and 
eCRF pages. 
2. Immediately (no later than 24 hours) contact the sponsor to inform them of the pregnancy 
occurrence by fax/email and discuss further steps to be taken. 
 
GALDERMA R&D  
Name 
Title 
 
 
Address 
 
 
 
Tel. during office hours 
 
Tel. Outside  office hours 
 
Fax 
 
Email 
pharmacovigilance@galderma.com 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 71 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
3. Complete, as fully as possible, the Pregnancy Surveillance Form – Part I: History and start 
of pregnancy - provided by the CRA at the beginning of the clinical trial (it is also available in 
the eCRF system as pdf document), and fax or send by email within 24 hours to the sponsor. 
4. Monitor and record the progress of the pregnancy until its outcome.  Contact the subject’s regular 
physician (general practitioner or gynecologist) or hospital staff to obtain further details and ask 
regular follow-up information. 
5. Inform the sponsor of the progress by tri-monthly updates up to the final outcome of the 
pregnancy. For all the additional follow-up evaluations, fax or send by e-mail the additional 
follow-up information to the sponsor within 24 hours of receipt of the information.  If the subject 
can no longer be reached (lost to follow-up), documentation of the non-response/contact with two 
phone calls and a letter (certified with return receipt) is required. 
6. At outcome of pregnancy, complete as fully as possible the Pregnancy Surveillance Form – 
Part II: Course and outcome of pregnancy and send it by fax or by email to the sponsor within 
24 hours following investigator’s or site personnel becoming aware of the outcome of the 
pregnancy. 
7. If the pregnancy leads to an abortion (voluntary abortion, spontaneous abortion or therapeutic 
abortion), in utero death or congenital anomaly, follow the procedure for declaration of an SAE 
(see section 8.4). 
8. If the investigator is informed of a developmental abnormality of the baby, even a long time after 
the end of the clinical trial, he/she must inform the sponsor and follow the procedure for 
declaration of an SAE (see section 8.4). 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 72 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
9 
STATISTICAL METHODS PLANNED 
9.1 
STATISTICAL AND ANALYTICAL PLANS 
A Statistical Analysis Plan (SAP) will be developed as a separate document. The SAP will contain a 
more detailed and technical description of specific data conventions, calculations and of statistical 
procedures for executing the analyses that are specified in the sections of the clinical trial protocol 
below. The SAP will be finalized prior to database lock and unblinding. Any change made to the 
finalized SAP will be documented in the clinical trial report. 
 
 
9.1.1 Variables to be statistically analyzed 
 
The following variables will be analyzed: 
 
Primary efficacy endpoint:  
 Total atrophic acne scar count per half-face at week 24 
 
Secondary efficacy endpoints:  
 Total atrophic acne scar count per half-face at each post-baseline visit (except week 24) 
 Percent change from Baseline in total atrophic acne scar count per half-face at each post-
baseline visit 
 SGA per half-face at each post-baseline visit 
 Investigator’s preference on overall scar severity at week 12, week 24, early termination during 
part I 
 Percent change from Baseline in total lesion count per half-face at each post-baseline visit 
 Percent change from Baseline in inflammatory lesion count per half-face at each post-baseline 
visit 
 Percent change from Baseline in non-inflammatory lesion count per half-face at each post-
baseline visit¨ 
 IGA per half-face at each post-baseline visit 
 
Exploratory efficacy endpoints:  
 Investigator’s assessment of skin roughness of each half-face at Baseline, week 12, week 24, 
week 48, early termination 
 Investigator’s assessment of skin texture change per half-face at week 12, week 24, week 48, 
early termination 
 Skin microrelief variables: percent change from Baseline per half-face at week 24, week 48, 
early termination (if early termination occurs after week 8) 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 73 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
Safety endpoints:  
 Incidence of adverse events 
 Local tolerability: percent of subjects across scores at each post-baseline visit 
 
PRO endpoints:  
 Acne scar appearance using the SCARS questionnaire at baseline, week 12, week 24, week 48, 
early termination, for each half-face  
 Subject satisfaction questionnaire at week 24, week 48, early termination 
 
9.1.2 Populations analyzed, evaluability and limitations / evaluation of bias 
 
The statistical analyses will be performed based on the following subject populations. The definition 
of the populations will be finalized after a blind data review meeting. 
9.1.2.1 The Per Protocol efficacy population (PP) 
 
This population will consist of all enrolled and randomized subjects, except subjects who have major 
deviations from the protocol. Major deviations will be defined during a data review meeting after 
data entry and before unblinding the clinical trial treatment. Major protocol deviations will be 
considered as having a possible effect on the interpretation of primary efficacy results and may 
include: inclusion criteria not respected, non-available efficacy assessment, interfering therapy at 
inclusion, etc.  
The primary efficacy endpoint will be analyzed based on this population. 
9.1.2.2 The Intent-to-Treat efficacy population (ITT) 
 
This population will consist of the entire population enrolled and randomized (i.e., assigned a kit 
number). The ITT population will be used for all variables except the safety variables. 
 
9.1.2.3 The Safety population (All patients treated [APT]) 
 
This population will consist of the Intent-to-Treat population, after exclusion of subjects who never 
used the treatment with certainty based on monitoring report. The APT population will be only used 
for the safety variables. 
 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 74 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
9.1.2.4 Missing values 
 
The last observation carried forward (LOCF) method will be used to impute missing values of acne 
scar and lesion counts and global assessment scores (SGA and IGA) during part I. If no post-baseline 
data are available, baseline will be carried forward. The other missing values of part I and the data 
collected during part II will not be replaced (observed data). 
 
 
9.1.3 Data presentation and graphics 
 
All continuous data will be summarized using usual statistics: number of values, mean, median, 
standard deviation, minimum and maximum, and by frequency distribution (n, %) for qualitative 
data. For ordinal data, both frequency distribution and usual statistics will be presented. Tables will 
be presented by investigational product, bilateral difference and visit (when applicable).  
 
Therapies that have been stopped before the baseline visit will be presented as prior therapies. Those 
reported at baseline and still continuing after baseline will be classified as concomitant therapies. 
 
The adverse events will be descriptively summarized (n, %) for the safety population (APT). The 
adverse events will be descriptively summarized (n, %) by relationship to the investigational 
products within System Organ Class (SOC) and preferred term (MedDRA). Subjects will be 
descriptively summarized (n, %) by intensity (i.e. mild, moderate and severe) of adverse events, SOC 
and preferred terms. Deaths and serious adverse events will be reported as well as withdrawals due to 
adverse events. A subject will be counted only once per System Organ Class (SOC) and only once 
per preferred term even if more than one occurrence of an event was reported within a SOC or 
preferred term. In the summary by categories of intensity, the adverse event with the highest 
intensity will be used. The subject will be counted only once per SOC (highest intensity whatever the 
AE within the SOC) and once per preferred term (highest intensity whatever the AE within the 
preferred term).  
 
9.1.4 Statistical analyses 
 
The primary objective of this trial is to demonstrate the superiority of Adapalene 0.3% - BPO 2.5% 
gel compared to its vehicle, in terms of total atrophic acne scar count at week 24. The mean bilateral 
difference between products of primary efficacy endpoint will be analyzed by using the Wilcoxon 
Rank Signed test, testing the hypothesis of equality. The p-value will have to be inferior to 0.05 at 
week 24, on ITT/LOCF population.  Per Protocol analysis will be also performed to assess the 
robustness of the results obtained on the ITT/LOCF population. 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 75 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
The other efficacy variables of part I will be analyzed similarly as the primary analysis on the 
appropriate population. Each test will be two-sided, at the 0.050 significance level. 
 
The subject characteristics (previous medication, concomitant medication, demographics, baseline 
characteristics…), lesion counts, microrelief, adverse events, local tolerability and questionnaires and 
all variables of part II will be summarized by descriptive statistics (usual statistics and frequency 
distribution). 
 
9.1.5 Interim analysis 
 
Interim analysis will be performed when all subjects will have completed the week 24 visit (Part I). 
For this interim analysis, all available variables will be analyzed. This interim analysis is dedicated 
to provide the statistical results and is not meant to condition to any premature study termination. As 
all statistical analyses were planned during part I, this interim analysis will have no impact on the 
type I error, and the efficacy results will be considered as final. 
 
9.2 
SAMPLE SIZE DETERMINATION 
9.2.1 Historical data and assumptions 
 
Results from a previous intra-individual trial designed as a right-left comparison of Adapalene 0.1% 
- BPO 2.5% gel versus vehicle gel in acne subjects (protocol RD.03.SPR.40183E) showed a standard 
deviation (SD) of the bilateral differences in terms of total atrophic acne scar count at week 24 of 
around 4.8 with a mean bilateral difference around 2. 
9.2.2 Sample size calculation 
 
Using the historical data mentioned above, 50 evaluable subjects will be required, with 80% power. 
To allow about 20% rate of subjects excluded from analysis (major deviation, drop out, lost to 
follow-up, etc.) at week 24, 60 subjects should be enrolled. 
 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 76 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
10 
TRAINING / MONITORING / DATA MANAGEMENT / QUALITY ASSURANCE 
 
A contract research organization (CRO) will be responsible for monitoring the clinical trial and the 
sponsor may perform co-monitoring visits at selected sites. 
10.1 
PERSONNEL TRAINING 
Clinical Research Associates (CRA) will be trained prior to clinical trial initiation and as needed 
during the trial (in particular in case of protocol amendment). During this training, an overview of 
the disease of interest and treatment will be presented. Specific monitoring guidelines and procedures 
to be followed during monitoring visits will be discussed. 
 
Initiation visits will be conducted with all principal investigators and site teams. During these visits, 
an extensive review and discussion of the protocol, procedures and eCRF will be conducted. 
Evaluation scales will also be reviewed. 
 
A monitoring manual will be provided to each CRA as an additional reference tool.  
 
An eCRF completion guideline will be provided to each CRA and site. These guidelines will contain 
instructions on how to fill in the eCRF with some examples in order to standardize the eCRF 
completion as much as possible. 
 
A trial reference manual will be provided to each site as an additional reference tool. These 
guidelines will contain key CRO and sponsor contacts and phone numbers and specific instructions 
for site in order to standardize as much as possible the assessments performed during the clinical 
trial. A manual will also be provided to the product dispenser, with specific instructions detailing use 
of the “study companion” tablet. 
 
Furthermore during the investigator meeting a specific training on scars assessments will be 
conducted. 
10.2 
CLINICAL MONITORING  
The conduct of the clinical trial will be closely monitored by GALDERMA R&D or representatives 
to verify the adherence to the clinical trial protocol, ICH-GCP regulations, applicable standard 
operating procedures (SOPs), guidelines, and all local regulations.  
 
The investigator will allow representatives of GALDERMA R&D to have direct access to all clinical 
trial records, eCRFs, corresponding subject medical records, investigational product dispensing 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 77 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
records and investigational product storage area, site facilities and any other documents considered 
as source documentation. 
 
The investigator also agrees to assist the CRO/ GALDERMA R&D representatives, if required. 
10.3 
DATA MANAGEMENT 
A CRO will be responsible for data management in connection with the sponsor’s data manager. 
 
All data management procedures will be detailed in the Data Management Plan (DMP).  
The DMP will describe the Clinical Data Management System (CDMS) that will be used to collect 
and validate data. Computerized edit checks and review processes will be performed on an ongoing 
basis as outlined in the DMP until all data discrepancies are resolved. 
After all data discrepancies are resolved, coding is approved, and subject evaluability has been 
determined, the data will be exported to SAS datasets and will be locked (there will be one lock for 
Part I and one lock for Part II). 
After unblinding (part I only), the locked SAS database will be used to generate subject listings, 
tabulations and analyses.  
 
The data may be audited by the sponsor and/or CRO Quality Assurance department before or after 
the first statistical analysis results on the primary criteria. 
10.4 
QUALITY ASSURANCE / AUDIT / INSPECTION 
The clinical trial will be conducted under the sponsorship of GALDERMA R&D in compliance with 
all appropriate local regulations as well as ICH guidelines and in accordance with the SOPs for 
clinical trial conduct and monitoring from GALDERMA R&D and/or CRO. 
Audits of clinical trial sites may be conducted by GALDERMA R&D /CRO representatives, and 
inspection may be performed by Regulatory Authority inspectorates or IRBs/ECs before, during, or 
after the clinical trial.   
The investigator will allow and assist the GALDERMA R&D /CRO representatives, IRBs/ECs and 
any regulatory agency to have direct access to all requested clinical trial-related records. 
For the audits performed by, or on behalf of, GALDERMA R&D auditors, audit certificate(s) will be 
provided by Quality Assurance. 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 78 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
11 
ETHICS AND GENERAL CLINICAL TRIAL CONDUCT CONSIDERATIONS 
11.1 
INSTITUTIONAL REVIEW BOARD (IRB) OR ETHICS COMMITTEE (EC) 
This clinical trial protocol will be reviewed and approved by IRBs/ECs prior to clinical trial 
initiation. 
 
This protocol may be modified at any time for ethical, medical or scientific reasons. Such 
modifications will be documented by a clinical protocol amendment and, if deemed necessary, an 
amended protocol will be issued. 
 
Before implementation, the amendment should be submitted and approved by applicable IRBs/ECs 
and, if required by the Regulatory Authority(ies). 
 
No amendment will be required for modification(s) due to a change in logistical or administrative 
aspects of the clinical trial (e.g., change in monitors, change of telephone numbers). In such a case, 
the appropriate institution(s) and/or person(s) will be directly notified of the changes. 
11.2 
ETHICAL CONDUCT OF THE CLINICAL TRIAL 
This clinical trial will be conducted in accordance with the ethical principles originating from the 
Declaration of HELSINKI declaration (1964) and subsequent amendments, the International 
Conference on Harmonization (ICH), Good Clinical Practice (GCP) and in compliance with local 
regulatory requirements. 
11.3 
SUBJECT INFORMATION SHEET / INFORMED CONSENT 
All subjects who participate in this trial will be fully informed about the clinical trial in accordance 
with the applicable regulations and GCP guidelines and in accordance with local legal requirements.  
 
The Informed Consent Form (including appropriate Assent Form for children (aged 16 to 17) and as 
applicable, photograph release form or skin replica consent) approved by an IRB/EC, will be fully 
explained to the subject and parent/guardian if applicable. There will be one ICF for part I (to be 
signed at the beginning of the trial, before or at the baseline visit) and one ICF for part II (to be 
signed by the subject at the end of part I, if the subject is considered for part II by the investigator 
and if s/he is willing to participate to part II). 
 
Prior to any clinical trial procedures, the subject and parent/guardian will sign and date the Informed 
Consent Form(s) which is written in the local language. A copy of the signed and dated form(s) will 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 79 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
be given to the subject and parent/guardian. The investigator is responsible for maintaining each 
subject’s Informed Consent Form(s) in the investigator's site file (ISF) and providing each subject 
and parent/guardian with a copy of the consent form. 
 
The Informed Consent Form including photograph release form approved by an IRB/EC will be fully 
explained to the subject and parent/guardian. 
11.4 
CONTRACTUAL REQUIREMENTS 
A contractual agreement will be signed between the CRO/sponsor and each investigator/institution.  
This document will contain supplementary information, including financial terms, confidentiality, 
the clinical trial schedule, third party responsibility, and publication rights. 
11.5 
DATA COLLECTION AND ARCHIVING 
11.5.1 Data Collection 
 
The investigator must maintain required records on all clinical trial subjects.  
Data for this clinical trial will be recorded in the subject’s source documents, in the product 
dispensation logs and in the “study companion” tablet allocation log.  
 
All data recorded in the documents described above should be recorded completely, promptly, and 
legibly using a pen (not a pencil).  
 
Each time a new subject is enrolled, the “study companion” tablet allocation log will be faxed or 
emailed to Triacys. The real-time data obtained through the “study companion” tablets will be 
automatically transferred to Triacys servers using specific software elaborated by Triacys. A copy of 
the videos taken by the subject will be maintained locally by the product dispenser during the trial 
and eventually destroyed once reconciliation with the central database will have been performed. 
Special attention will be brought to the videos in order to avoid possible use of those by non-
qualified personnel or for reasons other than those related to the trial and indicated in the present 
protocol. 
 
11.5.2 Source documentation 
 
Investigators must keep accurate separate records (other than the eCRF) of all subjects' visits, and all 
procedures done, being sure to include all pertinent clinical trial related information from which 
eCRF data will be recorded.  
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 80 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
A statement should be made on subject’s medical notes indicating that the subject has been 
enrolled in GALDERMA R&D protocol RD.03.SPR.105061 and has provided dated and signed 
informed consent and assent if appropriate.  
 
All adverse events with the associated concomitant therapies must be thoroughly documented. 
Results of any diagnostic tests conducted during the clinical trial will be included in the source 
documentation. 
 
Telephone conversations with the subjects and/or CRO/GALDERMA R&D concerning the clinical 
trial may be recorded and kept on file.  
 
Once the images from the “study companion” tablets will have been analyzed by qualified operators 
from Triacys and the report issued by Triacys finalized, they will be destroyed. In no case, personnel 
other than the qualified operators will have access to the images. The report will be kept on site in 
the ISF as transcription of the original source data (the videos). 
 
11.5.3 Archives 
 
All pertinent data, samples, photos, questionnaires, correspondence, original or amended protocol, all 
reports and all other material relating to the clinical trial will be maintained securely in 
GALDERMA R&D / Investigator/Institution archives for the legally-required duration of archiving. 
 
If the investigator retires, relocates, or for any other reason withdraws from the responsibility of 
keeping the clinical trial records, custody must be transferred to a person who will accept the 
responsibility. The sponsor must be notified in writing of the name and address of the new custodian. 
 
A copy of the trial data obtained via the analysis of the videos taken with the “study companion” 
tablets (the compliance report) will be maintained for a period of 25 years. By contrast, the images 
will not be maintained after the analysis is completed and the final compliance report is finalized. 
11.6 
INSURANCE 
A certificate attesting third party coverage of CRO/GALDERMA R&D will be provided upon 
request.  
 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 81 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
12 
REFERENCE LIST 
 
Bulengo-Ransby, SM, et al. 1993. Topical tretinoin (retinoic acid) therapy for hyperpigmented 
lesions caused by inflammation of the skin in black patients. N Engl J Med. 1993, Vol. 328, 20, pp. 
1438-1443. 
Cunliffe, W J and Gould, D J. 1979. Prevalence of facial acne vulgaris in late adolescence and in 
adults. BMJ. 1979, Vol. 1, pp. 1109-1110. 
Do, T T, et al. 2008. Computer-assisted alignment and tracking of acne lesions indicate that most 
inflammatory lesions arise from comedones and de novo. J Am Acad Dermatol. 2008, Vol. 58, pp. 
603-608. 
Fabbrocini, G, et al. 2010. Acne Scars: Pathogenesis, Classification and Treatment. Dermatology 
Research and Practice. 2010, pp. 1-13. 
Fisher, G J, et al. 2000. c-Jun-dependent inhibition of cutaneous procollagen transcription following 
ultraviolet irradiation is reversed by all-trans retinoic acid. J Clin Invest. 2000, Vol. 106, pp. 663-
670. 
Fitzpatrick, T B, et al. 1993. Dermatology in general medicine. 1993. pp. 1689-1716. Vols. 1, 
Chap. 137. 
Goodman, G J. 2011. Treatment of acne scarring. Int J Dermatol. 2011, Vol. 50, pp. 1179-1194. 
Goodman, GJ and Baron, JA. 2006(b). Postacne scarring – a qualitative global scarring grading 
system. Dermatol Surg. 2006(b), Vol. 32, pp. 1458-1466. 
—. 2006(a). Postacne scarring – a quantitative global scarring grading system. Journal of Cosmetic 
Dermatology. 2006(a), Vol. 5, pp. 48-52. 
Griffiths, C EM, Kang, S and Ellis, C N. 1995. Two concentrations of topical tretinoin (retinoic 
acid) cause similar improvement of photoaging but different degrees of irritation: a double-blind, 
vehicle-controlled comparison of tretinoin 0.1% and 0.025% creams. Arch Dermatol. 1995, Vol. 
131, pp. 1037-1044. 
Grimes, P and Callender, V. 2006. Tazarotene cream for postinflammatory hyperpigmentation and 
acne vulgaris in darker skin: a double-blind, randomized, vehicle-controlled study. Cutis. 2006, Vol. 
77, 1, pp. 45-50. 
Jacob, CI and Dover, J S. 2001. Acne scarring: a classification system and review of treatment 
options. J Am Acad Dermatol. 2001, Vol. 45, 1, pp. 109-117. 
Jacyk, WK. 2001. Adapalene in the treatment of African patients. J Eur Acad Dermatol Venereol. 
2001, Vol. 15, Suppl 3, pp. 37-42. 
Jemec, G B and Jemec, B. 2004. Treatment of Scars. Clinics in Dermatology. 2004, Vol. 22, pp. 
434-438. 
Kang, S and Voorhees, J J. 1998. Photoaging therapy with topical tretinoin: an evidence-based 
analysis. J Am Acad Dermatol. 1998, Vol. 39, pp. S55-61. 
Kang, S, Cho, S and Chung, J H. 2005. Inflammation and extracellular matrix degradation 
mediated by activated transcription factors NFkB and AP-1 in inflammatory acne lesions in vivo. Am 
J Pathol. 2005, Vol. 166, pp. 1691-1699. 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 82 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
Kang, S, et al. 2001. Tazarotene cream for the treatment of facial photodamage: A multicenter, 
Investigator-masked, randomized, vehicle-controlled, parallel comparison of tazarotene 0.01%, 
0.025%, 0.05%, and 0.1% creams and tretinoin 0.05% emollient cream applied once-daily f. Arch 
Dermatol. 2001, Vol. 137, pp. 1597-1604. 
Kang, S, Fisher, G J and Voorhees, J J. 1997. Photoaging and topical tretinoin: therapy, 
pathogenesis, and prevention. Arch Dermatol. 1997, Vol. 133, pp. 1280-1284. 
Kang, S, Goldfarb, M T and Weiss, J S. 2003. Assessment of Adapalene gel for the treatment of 
actinic keratoses and lentigines: A randomized trial. J Am Acad Dermatol. 2003, Vol. 49, 1, pp. 83-
90. 
Koo , J Y and Smith, L L. 1991. Psychologic aspects of acne. Pediatr Dermatol. 1991, Vol. 8, 3, 
pp. 185-188. 
Kraining, K K and Odland, G F. 1979. Prevalence, morbidity, and cost of dermatologic diseases. J 
Invest Dermatol. 1979, Vol. 73, pp. 395-513. 
Layton, A M, Henderson, C A and Cunliffe, W J. 1994. A clinical evaluation of acne scarring and 
its incidence. Clinical and Experimental Dermatology. 1994, Vol. 19, pp. 303-308. 
Layton, A M, Seukeran, D and Cunliffe, W J. 1997. Scarred for life? Dermatology. 1997, Vol. 
195, suppl 1, pp. 15-21. 
Leyden, J J. 1995. New understandings of the pathogenesis of acne. J Am Acad Dermatol. 1995, 
Vol. 32, pp. S15-S25. 
Pandya, A G and Guevara, I L. 2000. Disorders of hyperpigmentation. Dermatol Clinics. 2000, 
Vol. 18, 1, pp. 91-98. 
Papakonstantinou, E, Aletras, A and Glass, E. 2005. Matrix Metallonproteinases of epithelial 
origin in facial sebum of patients with acne and their regulations by isotretinoin. J Invest Dermatol. 
2005, Vol. 125, pp. 673-684. 
Philips, T J, Gottlieb, A B and Leyden, J J. 2002. Efficacy of 0.1% Tazarotene cream for the 
treatment of photodamange. Arch Dermatol. 2002, Vol. 138, pp. 1486-1493. 
Spiewak, R. 2008. Patch Testing for Contact Allergy and Allergic Contact Dermatitis. The Open 
Allergy Journal. 2008, Vol. 1, pp. 42-51. 
Taylor, S, et al. 2002. Acne vulgaris in skin of color. J Am Acad Dermatol. 2002, Vol. 46, 2, pp. 
S98 – S106. 
Trivedi, N R. 2006. Gene Array Expression Profiling in Acne Lesions. J of Invest Dermatol. 2006, 
Vol. 126, 5, pp. 1071-1079. 
Usatine, RP, Quan, MA and Strick, R. 1998. Acne vulgaris: a treatment update. Hosp Pract. 1998, 
Vol. 33, pp. 111-127. 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 83 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
13 ATTACHMENTS 
13.1 
APPENDIX 1  
SCARS questionnaire 
(Self-assessment of Clinical Acne-Related Scars) 
 
 
 
 
RIGHT-HAND SIDE OF THE FACE 
Part 1 
Please remove all make-up and facial jewellery/piercings, and tie back any loose hair covering your face 
before answering this questionnaire. 
Please begin by answering the questions below.  These questions will help you understand the difference 
between active acne and atrophic acne scars. 
 
The following question asks you about atrophic acne scars only.  Please do not consider active acne (zits, 
breakouts, pimples, whiteheads, or blackheads), scabs, or flat red or dark marks. 
a) Active acne includes zits, breakouts, pimples, whiteheads, and blackheads. 
When looking at the right-hand side of your face in the mirror right now, do you see zits, 
breakouts, pimples, whiteheads, or blackheads? 
Yes / No (please circle one) 
If yes, please rate the severity of the zits, breakouts, pimples, whiteheads, or blackheads 
on the right-hand side of your face by putting a vertical line in the place that best describes 
your acne. 
No active acne 
 
Very severe active acne 
0 
 
 
 
10 
 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 84 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
 
 
Part 2 
 
The following questions ask you about atrophic acne scars only.  Remember, atrophic acne scars are indents 
or holes in the skin from previous active acne.  Please do not consider active acne (zits, breakouts, pimples, 
whiteheads, or blackheads), scabs, or flat red or dark marks.  
Please read each question, then look in the mirror and think about the indents or holes on the right-hand side 
of your face, and then answer the question.  Please mark an “X” in the box (
) that best describes how the 
indents or holes on your face look RIGHT NOW. 
There are no right or wrong answers to these questions.  If you want to change your answer, please cross out 
your original answer and mark an “X” in the correct box. 
Please choose only one response. 
1. When looking at the right-hand side of your face in the mirror right now, how much of your face looks 
covered by indents or holes? 
Almost none 
of the right-hand 
side of face 
A little 
of the right-hand 
side of face 
Some 
of the right-hand 
side of face 
A lot 
of the right-hand 
side of face 
Almost all 
of the right-hand 
side of face 
 
 
 
 
 
 
b) Atrophic acne scars are indents or holes in the skin from previous active acne (not from 
injury, scratching or picking). 
When looking at the right-hand side of your face in the mirror right now, do you see indents 
or holes in the skin from previous active acne? 
Yes / No (please circle one) 
 
If you answered “No” for this question, please go to page 4 to answer questions for the left-
hand side of your face.  
If yes, please rate the severity of the indents or holes on the right-hand side of your face by 
putting a vertical line in the place that best describes your scars. 
No indents 
or holes 
 
Very severe 
indents or holes 
0 
 
 
 
10 
 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 85 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
2. When looking at the right-hand side of your face in the mirror right now, how small or large do the 
individual indents or holes look? 
Very small 
Small 
Moderate 
Large 
Very large 
 
 
 
 
 
 
3. When looking at the right-hand side of your face in the mirror right now, how many indents or holes do 
you see? 
Very few 
indents or holes 
A few 
indents or holes 
Some 
indents or holes 
Quite a lot of 
indents or holes 
Many 
indents or holes 
 
 
 
 
 
 
4. When looking at the right-hand side of your face in the mirror right now, how deep do the individual 
indents or holes look? 
Not at all 
deep 
A little 
deep 
Moderately 
deep 
Very 
deep  
Extremely 
deep 
 
 
 
 
 
 
5. When looking at the right-hand side of your face in the mirror right now, how visible are the indents or 
holes to you? 
Not at all 
visible 
A little 
visible 
Moderately 
visible 
Very 
visible 
Extremely 
visible 
 
 
 
 
 
 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 86 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
 
LEFT-HAND SIDE OF THE FACE 
Part 3 
Please remove all make-up and facial jewellery/piercings, and tie back any loose hair covering your face 
before answering this questionnaire. 
Please begin by answering the questions below.  These questions will help you understand the difference 
between active acne and atrophic acne scars. 
 
The following question asks you about atrophic acne scars only.  Please do not consider active acne (zits, 
breakouts, pimples, whiteheads, or blackheads), scabs, or flat red or dark marks. 
 
a) Active acne includes zits, breakouts, pimples, whiteheads, and blackheads. 
When looking at the left-hand side of your face in the mirror right now, do you see zits, 
breakouts, pimples, whiteheads, or blackheads? 
Yes / No (please circle one) 
If yes, please rate the severity of the zits, breakouts, pimples, whiteheads, or blackheads on 
the left-hand side of your face by putting a vertical line in the place that best describes your 
acne. 
No active acne 
 
Very severe active acne 
0 
 
 
 
10 
 
 
 
b) Atrophic acne scars are indents or holes in the skin from previous active acne (not from 
injury, scratching or picking). 
When looking at the left-hand side of your face in the mirror right now, do you see indents or 
holes in the skin from previous active acne? 
Yes / No (please circle one) 
If you answered “No” for this question, you have completed the questionnaire. Thank you for 
your time.  
If yes, please rate the severity of the indents or holes on the left-hand side of your face by 
putting a vertical line in the place that best describes your scars. 
No indents 
or holes 
 
Very severe 
indents or holes 
0 
 
 
 
10 
 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 87 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
Part 4 
 
The following questions ask you about atrophic acne scars only.  Remember, atrophic acne scars are indents 
or holes in the skin from previous active acne.  Please do not consider active acne (zits, breakouts, pimples, 
whiteheads, or blackheads), scabs, or flat red or dark marks.  
Please read each question, then look in the mirror and think about the indents or holes on the left-hand side of 
your face, and then answer the question.  Please mark an “X” in the box (
) that best describes how the 
indents or holes on your face look RIGHT NOW. 
There are no right or wrong answers to these questions.  If you want to change your answer, please cross out 
your original answer and mark an “X” in the correct box. 
Please choose only one response. 
1. When looking at the left-hand side of your face in the mirror right now, how much of your face looks 
covered by indents or holes? 
Almost none 
of the left-hand 
side of face 
A little 
of the left-hand 
side of face 
Some 
of the left-hand 
side of face 
A lot 
of the left-hand 
side of face 
Almost all 
of the left-hand 
side of face 
 
 
 
 
 
 
2. When looking at the left-hand side of your face in the mirror right now, how small or large do the 
individual indents or holes look? 
Very small 
Small 
Moderate 
Large 
Very large 
 
 
 
 
 
 
3. When looking at the left-hand side of your face in the mirror right now, how many indents or holes do you 
see? 
Very few 
indents or holes 
A few 
indents or holes 
Some 
indents or holes 
Quite a lot of 
indents or holes 
Many 
indents or holes 
 
 
 
 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 88 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
4. When looking at the left-hand side of your face in the mirror right now, how deep do the individual 
indents or holes look? 
Not at all 
deep 
A little 
deep 
Moderately 
deep 
Very 
deep  
Extremely 
deep 
 
 
 
 
 
 
5. When looking at the left-hand side of your face in the mirror right now, how visible are the indents or 
holes to you? 
Not at all 
visible 
A little 
visible 
Moderately 
visible 
Very 
visible 
Extremely 
visible 
 
 
 
 
 
 
 
Thank you for your time. 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 89 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
13.2 
APPENDIX 2 
Subject satisfaction questionnaire – Part I 
 
INSTRUCTIONS: 
 
 
Please complete one questionnaire regarding the trial treatments you have been using in this trial. 
Please use a pen (not a pencil) to complete this questionnaire. Please give only ONE answer per 
question. 
 
There are no “Right” or “Wrong” answers. If you are unsure how to answer a question, please 
give the best answer you can.  
 
If you need to make a change, draw a line through the answer you would like to change, and then 
record your next response with a checkmark, put your initial and a date next to your correction. 
 
Your answers will not affect your participation in the trial and no prejudice will be shown 
towards you for completing this document. 
 
A - Questions about the acne treatment applied every evening 
Please answer for each side of your face.  
 
Left 
Right 
1. How bothered were you by the treatment side effects? 
Not bothered at all 
[  ] 
[  ] 
Bothered somewhat 
[  ] 
[  ] 
Bothered 
[  ] 
[  ] 
Bothered a great deal 
[  ] 
[  ] 
2. How satisfied were you with the time it took for treatment to work? 
Very satisfied 
[  ] 
[  ] 
Satisfied 
[  ] 
[  ] 
Somewhat satisfied 
[  ] 
[  ] 
Not satisfied 
[  ] 
[  ] 
3. How satisfied were you with the effectiveness of the treatment? 
Very satisfied 
[  ] 
[  ] 
Satisfied 
[  ] 
[  ] 
Somewhat satisfied 
[  ] 
[  ] 
Not satisfied 
[  ] 
[  ] 
4. Overall, are you satisfied with the treatment? 
Very satisfied 
[  ] 
[  ] 
Satisfied 
[  ] 
[  ] 
Somewhat satisfied 
[  ] 
[  ] 
Not satisfied 
[  ] 
[  ] 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 90 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
 
Left 
Right 
5. Would you consider using this treatment again? 
Yes 
[  ] 
[  ] 
No 
[  ] 
[  ] 
6. Did you use the provided moisturizing lotion? 
[  ] Yes 
[  ] No 
a. If yes, would you say (check as many answers as you wish) 
[  ] The moisturizer helped to reduce stinging / burning sensations 
[  ] The moisturizer helped you to be adherent to study treatments 
[  ] The moisturizer helped to reduce feeling of skin dryness 
[  ] The moisturizer was pleasant to use 
[  ] None of the above  
 
 
B - Questions about both skin care products Cetaphil® DermaControl™ Oil Control Foam Wash 
and Cetaphil® DermaControl™ Oil Control Moisturizer SPF 30 
 
1. Both skin care products were easy to incorporate into a daily routine: 
[  ] Strongly agree 
 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
 
[  ] Strongly disagree 
 
 
2. I would recommend  both skin care products to my family or friends: 
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
3. I felt - both skin care products helped my skin look healthier 
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 91 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
 
 
 
 
4. Using both skin care products made for acne made me feel more confident  
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
5. I felt - both skin care products made me feel more confident with my skin appearance 
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
 
6. I felt – both skin care products helped make a positive difference in the appearance of my skin 
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
 
7. I would keep using both skin care products 
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
  
8.  Both skin care products make my skin more hydrated 
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
 
 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 92 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
9. Both skin care products helped my skin to become less oily and less shiny 
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
10.  Both skin care products improved the texture of my skin  
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
 
11. Both skin care products are pleasant to use  
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 93 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
C - Questions about the cosmetic product Cetaphil® DermaControl™ Oil Control Foam Wash  
 
1. The Foam Wash left my skin with a clean healthy feeling:  
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
2. The Foam Wash provided deep cleansing without stripping the skin’s moisture:  
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
3. The Foam Wash rinsed off easily:  
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
4. The Foam Wash did not make my skin feel tight or dry:  
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 94 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
D - Questions about the cosmetic product Cetaphil® DermaControl™ Oil Control Moisturizer SPF 30 
 
1. The Moisturizer SPF 30 made my skin feel soft and smooth:  
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
2. The Moisturizer SPF 30 improved my skin’s texture:  
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
3. The Moisturizer SPF 30 left my skin feeling hydrated and protected:  
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
4. The Moisturizer SPF 30 provided a comforting sensation on the skin:  
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
 
 
Thank you for your time. 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 95 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
13.3 
APPENDIX 3 
Subject satisfaction questionnaire – Part II 
 
INSTRUCTIONS: 
 
 
Please complete one questionnaire regarding the trial treatments you have been using in this trial. 
Please use a pen (not a pencil) to complete this questionnaire. Please give only ONE answer per 
question. 
 
There are no “Right” or “Wrong” answers. If you are unsure how to answer a question, please 
give the best answer you can.  
 
If you need to make a change, draw a line through the answer you would like to change, and then 
record your next response with a checkmark, put your initial and a date next to your correction. 
 
Your answers will not affect your participation in the trial and no prejudice will be shown 
towards you for completing this document. 
 
A – Not Applicable 
 
B - Questions about both skin care products Cetaphil® DermaControl™ Oil Control Foam Wash 
and Cetaphil® DermaControl™ Oil Control Moisturizer SPF 30 
 
1. Both skin care products were easy to incorporate into a daily routine: 
[  ] Strongly agree 
 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
 
[  ] Strongly disagree 
 
 
2. I would recommend  both skin care products to my family or friends: 
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
3. I felt - both skin care products helped my skin look healthier 
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 96 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
[  ] Strongly disagree 
 
 
 
 
4. Using both skin care products made for acne made me feel more confident  
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
5. I felt - both skin care products made me feel more confident with my skin appearance 
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
 
6. I felt – both skin care products helped make a positive difference in the appearance of my skin 
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
 
7. I would keep using both skin care products 
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
  
8.  Both skin care products make my skin more hydrated 
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
 
 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 97 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
9. Both skin care products helped my skin to become less oily and less shiny 
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
10.  Both skin care products improved the texture of my skin  
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
 
11. Both skin care products are pleasant to use  
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 98 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
C - Questions about the cosmetic product Cetaphil® DermaControl™ Oil Control Foam Wash  
 
1. The Foam Wash left my skin with a clean healthy feeling:  
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
2. The Foam Wash provided deep cleansing without stripping the skin’s moisture:  
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
3. The Foam Wash rinsed off easily:  
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
4. The Foam Wash did not make my skin feel tight or dry:  
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
 
Protocol N° RD.03.SPR.105061 
 
Page 99 of 99 
CONFIDENTIAL 
 
 
RD.03.SPR.105061 Protocol Version 02 – 06-JUL-2016 FR 
 
D - Questions about the cosmetic product Cetaphil® DermaControl™ Oil Control Moisturizer SPF 30 
 
1. The Moisturizer SPF 30 made my skin feel soft and smooth:  
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
2. The Moisturizer SPF 30 improved my skin’s texture:  
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
3. The Moisturizer SPF 30 left my skin feeling hydrated and protected:  
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
4. The Moisturizer SPF 30 provided a comforting sensation on the skin:  
[  ] Strongly agree 
[  ] Agree 
[  ] Neither agree or disagree 
[  ] Disagree 
[  ] Strongly disagree 
 
 
 
Thank you for your time. 
 

SAP_001.pdf: 
Effect of Adapalene 0.3% - Benzoyl Peroxide 2.5% Gel Versus Vehicle Gel on the Risk of Formation of Atrophic 
Acne Scars in Moderate to Severe Acne Subjects
NCT Number: NCT02735421
Date: 27 June 2017


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 1 of 37 – FINAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
(6-MONTH (Week 24) AFTER BASELINE) 
EFFECT OF ADAPALENE 0.3% - BENZOYL PEROXIDE 2.5% GEL VERSUS 
VEHICLE GEL ON THE RISK OF FORMATION OF ATROPHIC ACNE SCARS IN 
MODERATE TO SEVERE ACNE SUBJECTS 
APPROVALS 
_________________________/____/____/____/ 
  
GALDERMA PHASE IV 
_________________________/____/____/____/ 
______________________/____/____/____/ 
 
 
GALDERMA PHASE IV  
GALDERMA PHASE IV 
Distribution: 
Original: GALDERMA RESEARCH & DEVELOPMENT Archives, Sophia-Antipolis site 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 2 of 37 – FINAL 
 
TABLE OF CONTENTS 
1. 
STUDY OBJECTIVE 
4 
2. 
INTERIM STATISTICAL ANALYSIS OBJECTIVE 
4 
3. 
INVESTIGATIONAL PLAN 
4 
3.1 
OVERALL STUDY DESIGN 
4 
3.2 
SAMPLE SIZE CONSIDERATION 
5 
3.2.1 
Historical data and assumptions 
5 
3.2.2 
Sample size calculation 
5 
4. 
ANALYZED VARIABLES 
5 
4.1 
EFFICACY VARIABLES 
5 
4.1.1 
Primary efficacy variable 
5 
4.1.2 
Secondary efficacy variables 
5 
4.1.3 
Exploratory efficacy variables 
6 
4.2 
PATIENT-REPORTED OUTCOMES VARIABLES 
7 
4.3 
SAFETY VARIABLES 
7 
5. 
POPULATIONS ANALYZED 
8 
5.1 
INTENT TO TREAT POPULATION (ITT) 
8 
5.2 
PER PROTOCOL POPULATION (PP) 
8 
5.3 
SAFETY POPULATION (APT) 
9 
5.4 
MISSING VALUES 
9 
6. 
STATISTICAL METHODS AND DATA CONSIDERATIONS 
9 
6.1 
DATA PRESENTATION 
9 
6.2 
STUDY SUBJECTS 
10 
6.2.1 
Subject disposition 
10 
6.2.2 
Protocol deviation 
10 
6.2.3 
Data sets analyzed 
10 
6.2.4 
Demographic data 
10 
6.2.5 
Medical history 
10 
6.2.6 
Medical history of acute rosacea (worsening) 
Erreur ! Signet non défini. 
6.2.7 
Previous and concomitant drug and procedure therapies 
10 
6.2.8 
Compliance 
11 
6.2.9 
Baseline disease characteristics 
11 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 3 of 37 – FINAL 
6.3 
EFFICACY ANALYSES 
11 
6.3.1 
Primary efficacy analyses 
11 
6.3.2 
Secondary efficacy analyses 
11 
6.3.3 
Exploratory efficacy analyses 
11 
6.4 
PATIENT-REPORTED OUTCOMES ANALYSES 
12 
6.5 
SAFETY ANALYSES 
12 
6.5.1 
Extent of exposure 
12 
6.5.1.1 
Quantity of product used 
Erreur ! Signet non défini. 
6.5.1.2 
Treatment duration 
Erreur ! Signet non défini. 
6.5.2 
Adverse Events 
12 
7. 
CHANGES FROM THE PROTOCOL ANALYSIS PLAN 
12 
APPENDIX 1: LIST AND FORMAT OF TABLES 
13 
8. 
TABLE SHELLS 
14 
14.1. Study Subjects 
14 
14.1.1. Conduct of the study 
14 
14.1.2. Subject characteristics 
15 
14.2. Efficacy analyses 
19 
14.2.1. Primary efficacy analyses 
19 
14.2.2. Secondary efficacy analyses 
20 
14.2.2.1. Atrophic acne scar 
20 
14.2.2.2. Acne lesions 
22 
14.2.3. Exploratory efficacy analyses 
24 
14.2.4. Patient-reported outcomes analyses 
27 
14.3 Safety analyses 
31 
4.1. Extent of Exposure 
31 
5.2. Adverse events 
Erreur ! Signet non défini. 
 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 4 of 37 – FINAL 
1. STUDY OBJECTIVE 
The purpose of this study was to evaluate the efficacy of Adapalene 0.3% - benzoyl peroxide 2.5% 
gel (ABPO Forte) versus vehicle gel on the risk of formation of atrophic acne scars in moderate to 
severe acne subjects. 
 
 
 
2. INTERIM STATISTICAL ANALYSIS OBJECTIVE 
The purpose of this interim analysis is to test the superior efficacy of ABPO Forte compared to its 
vehicle at week-24, in terms of Total atrophic acne scar per half-face (primary efficacy criterion). 
 
The interim analysis will be performed when all subjects have completed the week-24 visit. For 
this interim analysis, all available variables at week-24 will be analyzed. It will have no impact on 
the type I error as this corresponds to primary analysis. This interim analysis is dedicated to provide 
topline results and is not meant to condition to any premature study termination. 
 
 
 
3. INVESTIGATIONAL PLAN 
3.1 OVERALL STUDY DESIGN  
Part I: This study was to be conducted as a multi-center, randomized, investigator-blinded, and 
vehicle-controlled trial using intra-individual comparison (right half-face versus left half-face) 
involving subjects of any gender or race, aged 16 to 35 years inclusive, with moderate to severe 
acne vulgaris and atrophic acne scars, and meeting other specific eligibility criteria. 
 
A total of 60 subjects were to be enrolled at approximately 7 sites in Canada and France. 
Approximately 8-15 subjects were planned from each site. Subjects were to be treated for 24 weeks 
and each of their half-face randomized to one of the two following treatments: 
 
once-daily Adapalene 0.3% - BPO 2.5% gel. 
 
once-daily “Adapalene 0.3% - BPO 2.5%” vehicle gel . 
 
There were 8 study visits: at baseline, week 1, 4, 8, 12, 16, 20 and week 24. 
 
Part II: This is an open-label trial. At the decision of the investigator based on his/her medical 
assessment of efficacy during part I (effect on acne lesions and/or acne scars) and if the subject 
agrees, the subjects will have the possibility to continue to be treated with once-daily ABPO Forte 
for up to 24 additional weeks on the whole face with 2 additional visits, week 36 and 48 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 5 of 37 – FINAL 
 
3.2 SAMPLE SIZE CONSIDERATION 
3.2.1 Historical data and assumptions 
Results from a previous intra-individual trial designed as a right-left comparison of Adapalene 
0.1% - BPO 2.5% gel versus vehicle gel in acne subjects (protocol RD.03.SPR.40183E) showed a 
standard deviation (SD) of the bilateral differences in terms of total atrophic acne scar count at 
week 24 of around 4.8 with a mean bilateral difference around 2. 
3.2.2 Sample size calculation 
Using the historical data mentioned above, 50 evaluable subjects will be required, with 80% power. 
To allow about 20% rate of subjects excluded from analysis (major deviation, drop out, lost to 
follow-up, etc.) at week 24, 60 subjects should be enrolled. 
 
 
 
4. ANALYZED VARIABLES 
4.1 EFFICACY VARIABLES 
4.1.1 Primary efficacy variable 
 Total atrophic acne scar count per half-face at week 24: The scars were counted according to 
their size defined in 2 categories using 2- and 4-mm punch biopsy tools for size classification: 
scars 2-4 mm and scars > 4 mm.  
 
4.1.2 Secondary efficacy variables 
  Total atrophic acne scar count per half-face at each intermediate visit  
 
 Percent change from baseline in total atrophic acne scar count per half-face at each 
post-baseline visit 
 
 Investigator’s Scar Global Assessment (SGA) per half-face at each post-baseline visit: % of 
subject across score. The evaluator assessed the severity of atrophic acne scars of each 
half-face, performing a static (“snapshot”) evaluation of the severity based on the scale below: 
 
Grade 
Score 
Clinical Description 
Clear 
0 
No visible scars from acne 
Almost Clear 
1 
Hardly visible scars from 50 cm away 
Mild 
2 
Easily recognizable; less than half the affected face area* involved 
Moderate 
3 
More than half and less than 75% of the affected face area* involved 
Severe 
4 
More than 75% of the affected face area* affected  
* The affected face area corresponds to a half-face. 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 6 of 37 – FINAL 
 
 Investigator’s preference on overall scar severity at week 12 and at week 24/early termination: 
At week 12, week 24 and in case of early termination, the evaluator assessed his/her preference 
in terms of overall acne scars severity between the two half faces 
 
Overall efficacy 
(in terms of acne scars) 
Left a lot 
better 
than right 
Left a little bit 
better 
than right 
 
No preference 
Right a little bit 
better 
than left 
Right a lot 
better 
than left 
Score 
-2 
-1 
0 
1 
2 
 
 Percent change from baseline in total lesion count per half-face at each post-baseline visit: sum 
of inflammatory and non-inflammatory acne lesion count 
 
 Percent change from baseline in inflammatory lesion count per half-face at each post-baseline 
visit:  
 
 Percent change from baseline in non-inflammatory lesion count per half-face at each 
post-baseline visit:  
 
 Investigator’s Global Assessment (IGA) per half-face at each post-baseline visit: % of subject 
across score. The evaluator assessed the severity of acne for each half-face using the scale 
below and adapted for half-faces: 
 
Grade 
Score 
Clinical Description 
Clear 
0 
Clear skin with no inflammatory or non-inflammatory lesions 
Almost Clear 
1 
A few scattered comedones and a few small papules 
Mild 
2 
Easily recognizable; less than half the face is involved. Some comedones and some 
papules and pustules. 
Moderate 
3 
More than half of the face is involved. Many comedones, papules and pustules. One small 
nodule may be present. 
Severe 
4 
Entire face is involved. Covered with comedones, numerous papules and pustules. Few 
nodules may or may not be present. 
 
4.1.3 Exploratory efficacy variables 
 
 Investigator’s assessment of skin roughness per each half-face at baseline, week 12 and week 
24/early termination: The evaluator evaluated skin roughness for each half-face at baseline, 
week 12, week 24 and in case of early termination by using the five-point scale below: 
 
Category 
Score 
Description 
None 
0 
Very smooth 
Minimal 
1 
Smooth 
Mild 
2 
Somewhat smooth  
Moderate 
3 
Slightly rough  
Severe 
4 
Very rough  
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 7 of 37 – FINAL 
 
 Investigator’s assessment of skin texture change per half-face at week 12 and week 24/early 
termination: Overall facial skin texture change will be graded by the evaluator for each 
half-face at week 12, week 24 and in case of early termination as follows:  
 
Score 
Description 
0 
Worse 
1 
No change 
2 
1-25% = slight improvement 
3 
26-50% = moderate improvement 
4 
51-75% = marked improvement 
5 
76-90% = almost complete improvement 
6 
91-100% = complete improvement 
 
 Skin microrelief variables: percent change from Baseline per half-face at week 24/early 
termination 
 
 
4.2 PATIENT-REPORTED OUTCOMES VARIABLES 
 
 Acne scar questionnaire per each half-face at baseline, week 12 and week 24/early termination: 
using the SCARS questionnaire (Self-assessment of Clinical Acne Related Scars) 
 
 Subject’s satisfaction questionnaire per each half-face at week 24/early termination  
 
 
4.3 SAFETY VARIABLES 
 Adverse events: Incidence of adverse events - All clinical medical events, whether observed by 
the investigator or reported by the subject and whether or not thought to be study product 
-related were to be considered adverse events. 
 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 8 of 37 – FINAL 
 
 Local tolerability per half-face at each post-baseline visit: % of subjects across scores. 
Erythema, scaling, dryness, and stinging/burning were graded at each visit as follows 
(Stinging/Burning at the baseline visit should be assessed as none):  
 
Erythema – abnormal redness of the skin. 
0 
None 
No erythema 
1 
Mild 
Slight pinkness present 
2 
Moderate 
Definite redness, easily recognized 
3 
Severe 
Intense redness 
Scaling – abnormal shedding of the stratum corneum. 
0 
None 
No scaling 
1 
Mild 
Barely perceptible shedding, noticeable only on light scratching or rubbing 
2 
Moderate 
Obvious but not profuse shedding 
3 
Severe 
Heavy scale production 
Dryness – brittle and/or tight sensation. 
0 
None 
No dryness 
1 
Mild 
Slight but definite roughness 
2 
Moderate 
Moderate roughness 
3 
Severe 
Marked roughness 
Stinging/Burning – prickling pain sensation immediately after (within 5 minutes) dosing.   
0 
None 
No stinging/burning 
1 
Mild 
Slight warm, tingling/stinging sensation; not really bothersome 
2 
Moderate 
Definite warm, tingling/stinging sensation that is somewhat bothersome 
3 
Severe 
Hot, tingling/stinging sensation that has caused definite discomfort 
 
 
 
5. POPULATIONS ANALYZED 
The definition of the populations and the pooling center will be finalized after a blind data review 
meeting, during which the distribution of subjects per site will be reviewed. 
 
5.1 INTENT TO TREAT POPULATION (ITT) 
This population consists of the entire population enrolled and randomized (i.e., assigned a kit 
number). The ITT population will be used for all variables except the safety variables. 
 
 
5.2 PER PROTOCOL POPULATION (PP) 
The PP Population is defined as comprising the ITT subjects who have no major protocol 
deviations that will be refined during a blind review meeting. Only the primary efficacy endpoint 
will be analyzed based on this population.  
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 9 of 37 – FINAL 
 
5.3 SAFETY POPULATION (APT) 
This population consists of the intent-to-treat population, after exclusion of subjects who never 
took the treatment with certainty based on monitoring report. The APT population will be only used 
for the safety variables (AEs) 
 
 
5.4 MISSING VALUES 
In order to evaluate the effect of major deviations or of data exclusions, the last observation carried 
forward (LOCF) method will be used to impute missing values of acne scar and lesion counts and 
global assessment scores (SGA and IGA). If no post-baseline data are available, baseline will be 
carried forward. Thus, the number of subjects will not vary at each visit. The other missing values 
will not be replaced (observed data). 
 
 
 
6. STATISTICAL METHODS AND DATA CONSIDERATIONS 
SAS version 9.3 will be used for all analyses. All tests will be two-sided and significance will be 
declared at a 0.05 level. 
 
6.1 DATA PRESENTATION 
All continuous data will be summarized at each visit using usual statistics: number of values, mean, 
median, standard deviation, minimum and maximum, and by frequency distribution (n, %) for 
qualitative data. For ordinal data, both frequency distribution and usual statistics will be presented.  
 
Therapies that have been stopped before the baseline visit will be presented as prior therapies. 
Those reported at baseline and still continuing after baseline will be classified as concomitant 
therapies. 
 
The adverse events will be descriptively summarized (n, %). All summaries are based on the safety 
population (APT). The adverse events will be descriptively summarized (n, %) by relationship to 
study treatments within System Organ Class (SOC) and preferred term (MedDRA). Subjects will 
be descriptively summarized (n, %) by intensity (i.e. mild, moderate and severe) of adverse event, 
SOC and preferred term. Deaths and serious adverse events will be reported as well as withdrawals 
due to adverse events. A subject will be counted once per System Organ Class (SOC) and once per 
preferred term even if more than one occurrence of an event was reported within a SOC or 
preferred term. In the summary by categories of intensity, the adverse event with the highest 
intensity will be used. The subject will be counted once per SOC (highest intensity whatever the 
AE within the SOC) and once per preferred term (highest intensity whatever the AE within the 
preferred term).  
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 10 of 37 – FINAL 
 
All tables will be presented by overall, treatment group (if appropriate), treatment bilateral 
difference (if appropriate) and by visit (if appropriate). For AE tables, if too few AEs are recorded, 
a listing can be provided including subject number, treatment group, SOC, preferred term, date of 
onset, severity, subject discontinued, outcome, date of resolution and relationship. 
 
 
6.2 STUDY SUBJECTS 
6.2.1 Subject disposition 
Normal completion as well as early discontinuation will be described on the ITT population.  
Reasons for withdrawals and normal completions will be summarized using frequency distribution 
(n, %).  All withdrawals will be detailed in a subject-by-subject listing. 
6.2.2 Protocol deviation 
Major protocol deviations will be summarized using frequency distribution (n, %) detailed in a 
subject-by-subject listing in the ITT population. 
6.2.3 Data sets analyzed 
Number of subjects included in each analysis (PP, ITT) and number of subjects included in the 
safety analysis will be presented. 
6.2.4 Demographic data 
Demographic data collected at baseline will be descriptively summarized for ITT population. 
6.2.5 Medical history  
Medical history is defined as the relevant or ongoing conditions and major illnesses/operations (at 
the discretion of the investigator). Acne disease duration will be descriptively summarized by 
duration classes on the ITT population. Frequency distribution of subjects with at least one 
previous and/or concomitant disease at baseline will be tabulated (n, %). 
6.2.6 Previous and concomitant drug and procedure therapies 
Previous drugs/procedures therapies are defined as drugs/procedures that have been stopped within 
the 6 months preceding the baseline visit and that may have an impact on inclusion/exclusion 
criteria. Concomitant drugs/procedures are defined as drugs/procedures taken between the baseline 
visit and the last visit. Previous and Concomitant drugs/procedures will be descriptively 
summarized on the ITT population, by ATC text for drugs and Lower Level Term for procedures. 
Frequency distribution of subjects with at least one previous drug/ procedure at baseline and/or 
with at least one concomitant drug/procedure will be tabulated (n, %). 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 11 of 37 – FINAL 
 
6.2.7 Compliance 
Compliance will be calculated as follows, based on the data from the Study Companion tablet 
analysis (a tablet on which the subjects record daily applications) complemented with information 
collected in the eCRF (treatment compliance pages). It will be considered that a subject has not 
used the product only when it will be confirmed (by Study Companion tablet analysis or in the 
eCRF). It will be summarized in terms of frequency percentages by products.  
 
 
6.2.8 Baseline disease characteristics 
The characteristics of the disease collected at baseline will be descriptively summarized on ITT 
population. 
 
 
6.3 EFFICACY ANALYSES 
6.3.1 Primary efficacy analyses 
The primary objective of this study is to demonstrate the superiority of Adapalene 0.3% - BPO 
2.5% gel compared to its vehicle, in terms of total atrophic acne scar count at week 24. The mean 
bilateral difference between products of primary efficacy endpoint will be analyzed by using the 
Wilcoxon Rank Signed test, testing the hypothesis of equality. The p-value will have to be inferior 
to 0.05 at week 24, on ITT/LOCF population.  Per Protocol analysis will be also performed to 
assess the robustness of the results obtained on the ITT/LOCF population. 
6.3.2 Secondary efficacy analyses 
The secondary efficacy variables will be analyzed similarly as primary analyses on ITT/LOCF 
population at each post-baseline evaluation time. Lesion counts will be only summarized by 
descriptive statistics. 
6.3.3 Exploratory efficacy analyses 
The exploratory efficacy variables will be analyzed similarly as primary analyses on ITT (data 
observed) population at each post-baseline evaluation time. 
 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 12 of 37 – FINAL 
 
6.4 PATIENT-REPORTED OUTCOMES ANALYSES 
All subject questionnaire will be descriptively summarized on ITT (data observed) population by 
investigational products and skin cares. 
 
 
6.5 SAFETY ANALYSES 
6.5.1 Extent of exposure 
Treatment duration will be calculated as the number of days between the date of first use and the 
date of the last use of study treatment. If the date of last use and/or last use are missing the date of 
first and/or last visit will be used respectively. 
6.5.2 Adverse Events 
The adverse events will be summarized (n, %) for APT population. Deaths and serious adverse 
events will be reported as well as withdrawals due to adverse events. 
 
 
 
7. CHANGES FROM THE PROTOCOL ANALYSIS PLAN 
There is no change from protocol analysis plan. 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 13 of 37 – FINAL 
APPENDIX 1: LIST AND FORMAT OF TABLES 
GENERAL FEATURES 
 
 Margins for portrait orientation 
 
• Top 
= 3.71 cm 
 
• Bottom 
= 3.17 cm 
 
• Left 
= 3 cm 
 
• Right 
= 1.4 cm 
 
• Heading 
= 2.41 cm 
 
• Footnote 
= 2.16 cm 
 
 Margins for landscape orientation 
 
• Top 
= 3 cm 
 
• Bottom 
= 1.4 cm 
 
• Left 
= 3.17 cm 
 
• Right 
= 3.71 cm 
 
• Heading 
= 2.16 cm 
 
• Footnote 
= 1.25 cm 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 14 of 37 – FINAL 
8. TABLE SHELLS 
14.1. Study Subjects 
14.1.1. Conduct of the study 
 
 
Table 1. Enrolment by center (ITT) 
e.g. 
 Total 
Center 1 (n,%) 
 
Center 2 (n,%) 
 
….. 
 
 
 
Table 2.1 Subjects who discontinued study and reason for discontinuation (ITT) 
e.g. 
 Total 
Randomized 
 
Premature discontinuation 
 
Adverse event 
 
Subject's request 
 
Protocol violation 
 
….. 
 
Completed the study 
 
 
Table 2.2. Listing of subjects who discontinued treatment and reason for discontinuation (ITT) 
(Included: investigator number, subject number and reason for discontinuation) 
 
 
 
Table 3. Adherence to the visit schedule in days (ITT) 
Total 
Nb of days between baseline and week 1 
 
N 
 
Mean±SD 
 
Median 
 
(Min,Max) 
 
…… 
 
Nb of days between baseline and week 24 
…… 
 
Nb of days between baseline and Endpoint* 
 
N 
 
Mean±SD 
 
Median 
 
(Min,Max) 
 
*Endpoint is defined as the last visit  
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 15 of 37 – FINAL 
Table 4.1 Major protocol deviations (ITT) 
 
Total 
e.g. 
Deviation 
n 
Subject 
n (%) 
AT LEAST ONE MAJOR DEVIATION 
 
 
Inclusion/exclusion criteria 
 
 
No visit after the baseline  
 
 
Compliance  
 
 
Forbidden concomitant therapies 
 
 
… 
 
 
 
Table 4.2. Listing of subjects and major protocol deviations (ITT) 
(Included: investigator number, subject number and deviation) 
 
 
 
Table 5. Data sets analysed 
Total 
Intent to treat population n 
Per Protocol population n (%)* 
Safety population n (%)* 
* Denominator is the number of subjects in the Intent to treat population 
 
 
14.1.2. Subject characteristics 
Table 6. Demographic data (ITT) 
 
Total 
Gender 
Male n(%) 
Female n(%) 
 
Age 
N 
Mean ±SD 
Median 
(Min,Max) 
 
 
≤ 18 years 
18 – 65 years 
≥ 65 years 
 
Race 
N 
White n (%) 
… 
 
Phototype 
I n (%) 
II n (%) 
…. 
 
 
 
 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 16 of 37 – FINAL 
Table 7. Medical history (ITT) 
 
Total 
(N=xxx) 
Acne vulgaris: duration in year  
N 
Less than 1 year n(%) 
Between 1 and xx years n(%) 
More than xx years n(%) 
Mean ±SD 
Median 
(Min,Max) 
 
With any relevant previous or/and concomitant disease/operation other than Acne vulgaris 
N 
Yes: n(%) 
No: n(%) 
 
 
 
Table 8. Previous drug therapies within the previous 6 months, by ATC text (ITT) 
Total 
(N=xxx) 
Subjects reporting at least one previous drug therapy (n,%) 
 
List all previous drug therapies by ATC category (n,%) 
 
The numbers in the columns cannot be added because a given subject could report more than one previous drug therapy 
 
Table 9. Previous procedure therapies within the previous 6 months, by Lower Level Term (ITT) 
Total 
(N=xxx) 
Subjects reporting at least one previous procedure therapy (n, %) 
 
List all previous procedures therapies by LLT. 
 
The numbers in the columns cannot be added because a given subject could report more than one previous procedure therapy. 
 
 
Table 10. Concomitant drug therapies by ATC text (ITT) 
Total 
(N=xxx) 
Subjects with at least one concomitant drug therapy (n, %) 
 
List all concomitant drug therapies by ATC category 
 
The numbers in the columns cannot be added because a given subject could report more than one concomitant drug therapy 
 
Table 11. Concomitant procedure therapies by Lower Level Term (ITT) 
Total 
(N=xxx) 
Subjects with at least one concomitant procedure therapy (n, %) 
 
List all concomitant procedure therapy by LLT. 
 
The numbers in the columns cannot be added because a given subject could report more than one concomitant procedure therapy 
 
 
Table 12. Compliance for investigational products (ITT) 
 
ABPO Forte 
Vehicle 
<25% of compliance n (%) 
[25%;50%[of compliance n (%) 
[50%;75%[of compliance n (%) 
>=75% of compliance n (%) 
 
 
 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 17 of 37 – FINAL 
 
Table 13. Baseline disease characteristics (ITT) 
 
ABPO Forte 
Vehicle 
ABPO Forte –Vehicle 
Acne scar counts (2-4 mm) 
N 
Mean ±SD 
Median 
Min,Max 
 
 
 
Acne scar counts (>4 mm) 
… 
 
 
 
Total acne scar counts  
…. 
 
 
 
Investigator’s Scar Global Assessment 
N 
…. 
-2: n (%) 
-1: n (%) 
 0: n (%) 
 1: n (%) 
 2: n (%) 
…. 
Mean ±SD 
Median 
Min,Max 
 
 
 
Tota lesion counts 
…… 
 
 
 
Inflammatory lesion counts 
…… 
 
 
 
Non-inflammatory lesion counts 
…… 
 
 
 
Nodule counts 
…… 
 
 
 
Investigator’s Global Assessment 
N 
…. 
-2: n (%) 
-1: n (%) 
 0: n (%) 
 1: n (%) 
 2: n (%) 
…. 
Mean ±SD 
Median 
Min,Max 
 
 
 
 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 18 of 37 – FINAL 
 
Table 14. Baseline skin aspect (ITT) 
 
ABPO Forte 
Vehicle 
ABPO Forte –Vehicle 
Skin roughness score 
N 
…. 
-2: n (%) 
-1: n (%) 
 0: n (%) 
 1: n (%) 
 2: n (%) 
…. 
Mean ±SD 
Median 
Min,Max 
 
 
 
Skin microrelief: Sa (µm) 
N 
Mean ±SD 
Median 
Min,Max 
 
 
 
Skin microrelief: Smax (µm) 
… 
 
 
 
 
Skin microrelief: Sz (µm) 
… 
 
 
 
 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 19 of 37 – FINAL 
 
14.2. Efficacy analyses 
14.2.1. Primary efficacy analyses 
 
Table 15. Total atrophic acne scar count: Descriptive and p-value at week 24 
ABPO Forte 
Vehicle 
ABPO Forte –Vehicle 
p-value (1) 
Total scar 
Week 24 (ITT/LOCF) 
 
 
 
 
N 
 
 
 
xxxx 
Mean ± SD 
 
 
 
 
Median 
 
 
 
 
(Min,Max) 
 
 
 
 
Week 24 (PP) 
 
 
 
 
N 
 
 
 
xxxx 
Mean ± SD 
 
 
 
 
Median 
 
 
 
 
(Min,Max) 
 
 
 
 
Scar 2-4mm 
Week 24 (ITT/LOCF) 
N 
Mean ±SD 
Median 
Min,Max 
 
 
 
 
xxxx 
Scar >4mm 
Week 24 (ITT/LOCF) 
N 
Mean ±SD 
Median 
Min,Max 
 
 
 
 
xxxx 
(1) Wilcoxon Rank Signed test 
 
 
Table 16. Total atrophic acne scar count at week 24: Descriptive by center (ITT/LOCF) 
ABPO Forte 
Vehicle 
ABPO Forte –Vehicle 
Center 1 
 
 
 
N 
 
 
 
Mean ± SD 
 
 
 
Median 
 
 
 
(Min,Max) 
 
 
 
Center 2 
 
 
 
N 
 
 
 
Mean ± SD 
 
 
 
Median 
 
 
 
(Min,Max) 
 
 
 
….. 
 
 
 
 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 20 of 37 – FINAL 
14.2.2. Secondary efficacy analyses 
14.2.2.1. 
Atrophic acne scar  
 
 
Table 17. Total atrophic acne scar count: Descriptive and p-value by visit (ITT/LOCF) 
ABPO Forte 
Vehicle 
ABPO Forte –Vehicle 
p-value (1) 
Baseline 
N 
Mean ±SD 
Median 
Min,Max 
 
 
 
NA 
Week 1 
 
 
 
 
N 
 
 
 
xxxx 
Mean ± SD 
 
 
 
 
Median 
 
 
 
 
(Min,Max) 
 
 
 
 
….. 
 
 
 
 
Week 20  
N 
Mean ±SD 
Median 
Min,Max 
 
 
 
 
xxxx 
(1) Wilcoxon Rank Signed test 
 
 
 
Table 18. Total atrophic acne scar % change from baseline: Descriptive and p-value by visit (ITT/LOCF) 
ABPO Forte 
Vehicle 
ABPO Forte –Vehicle 
p-value (1) 
Week 1 
 
 
 
 
N 
 
 
 
xxxx 
Mean ± SD 
 
 
 
 
Median 
 
 
 
 
(Min,Max) 
 
 
 
 
….. 
 
 
 
 
Week 24  
N 
Mean ±SD 
Median 
Min,Max 
 
 
 
 
xxxx 
(1) Wilcoxon Rank Signed test 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 21 of 37 – FINAL 
Table 19. Investigator’s Scar Global Assessment: Descriptive and p-value by visit (ITT/LOCF) 
ABPO Forte 
Vehicle 
ABPO Forte –Vehicle 
p-value (1) 
Baseline 
N 
Mean ±SD 
Median 
Min,Max 
 
 
 
NA 
….. 
 
 
 
 
Week 24  
N 
Mean ±SD 
Median 
Min,Max 
 
 
 
 
xxxx 
(1) Wilcoxon Rank Signed test 
 
Table 20. Investigator’s Scar Global Assessment: Descriptive by visit (ITT/LOCF) 
ABPO Forte 
Vehicle 
Baseline 
N 
2: Mild n (%) 
3: Moderate n (%) 
4: Severe n (%) 
Mean ±SD 
Median 
Min,Max 
 
 
 
….. 
 
 
Week 24  
N 
0: Clear n (%) 
1: Almost clear n (%) 
2: Mild n (%) 
3: Moderate n (%) 
4: Severe n (%) 
Mean ±SD 
Median 
Min,Max 
 
 
 
 
 
Table 21. Investigator’s preference on overall scar severity: Descriptive and p-value (ITT) 
 
Week 12 
 
ABPO Forte a lot better than Vehicle (n,%) 
ABPO Forte a little bit better Vehicle (n,%) 
No preference (n,%) 
Vehicle a little bit better ABPO Forte (n,%) 
Vehicle a lot better than ABPO Forte (n,%) 
p-value (1) 
 
Week 24/Early termination 
ABPO Forte a lot better than Vehicle (n,%) 
ABPO Forte a little bit better Vehicle (n,%) 
No preference (n,%) 
Vehicle a little bit better ABPO Forte (n,%) 
Vehicle a lot better than ABPO Forte (n,%) 
p-value (1) 
 
(1) Wilcoxon Rank Signed test  
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 22 of 37 – FINAL 
14.2.2.2. 
Acne lesions  
 
 
Table 22. Total lesion, % change from baseline: Descriptive and p-value by visit (ITT/LOCF) 
ABPO Forte 
Vehicle 
ABPO Forte –Vehicle 
p-value (1) 
Week 1 
 
 
 
 
N 
 
 
 
xxxx 
Mean ± SD 
 
 
 
 
Median 
 
 
 
 
(Min,Max) 
 
 
 
 
….. 
 
 
 
 
Week 24  
N 
Mean ±SD 
Median 
Min,Max 
 
 
 
 
xxxx 
(1) Wilcoxon Rank Signed test 
 
 
 
 
Table 23. Total lesion count: Descriptive by visit (ITT/LOCF) 
ABPO Forte 
Vehicle 
ABPO Forte –Vehicle 
Baseline 
N 
Mean ±SD 
Median 
Min,Max 
 
 
 
Week 1 
 
 
 
N 
 
 
 
Mean ± SD 
 
 
 
Median 
 
 
 
(Min,Max) 
 
 
 
….. 
 
 
 
Week 24  
N 
Mean ±SD 
Median 
Min,Max 
 
 
 
 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 23 of 37 – FINAL 
 
Table 24. Inflammatory lesion, % change from baseline: Descriptive and p-value by visit (ITT/LOCF) 
Table 25. Inflammatory lesion count: Descriptive by visit (ITT/LOCF) 
 
 
Table 26. Non-inflammatory lesion, % change from baseline: Descriptive and p-value by visit (ITT/LOCF) 
Table 27. Non-inflammatory lesion count: Descriptive by visit (ITT/LOCF) 
 
 
 
Table 28. Investigator Global Assessment: Descriptive and p-value by visit (ITT/LOCF)  
ABPO Forte 
Vehicle 
ABPO Forte –Vehicle 
p-value (1) 
Baseline 
N 
Mean ±SD 
Median 
Min,Max 
 
 
 
NA 
….. 
 
 
 
 
Week 24  
N 
Mean ±SD 
Median 
Min,Max 
 
 
 
 
xxxx 
 
 
Table 29. Investigator Global Assessment: Descriptive by visit (ITT/LOCF)  
ABPO Forte 
Vehicle 
Baseline 
N 
2: Mild n (%) 
3: Moderate n (%) 
4: Severe n (%) 
Mean ±SD 
Median 
Min,Max 
 
 
 
….. 
 
 
Week 24  
N 
0: Clear n (%) 
1: Almost clear n (%) 
2: Mild n (%) 
3: Moderate n (%) 
4: Severe n (%) 
Mean ±SD 
Median 
Min,Max 
 
 
 
 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 24 of 37 – FINAL 
14.2.3. Exploratory efficacy analyses 
 
 
Table 30. Skin roughness score: Descriptive and p-value by visit (ITT)  
ABPO Forte 
Vehicle 
ABPO Forte –Vehicle 
p-value (1) 
Baseline 
N 
Mean ±SD 
Median 
Min,Max 
 
 
 
NA 
Week 12 
N 
Mean ±SD 
Median 
Min,Max 
 
 
 
 
xxxx 
Week 24/Early termination 
N 
Mean ±SD 
Median 
Min,Max 
 
 
 
 
xxxx 
 
 
 
Table 31. Skin roughness score: Descriptive by visit (ITT)  
 
ABPO Forte 
Vehicle 
Baseline 
N 
1: None n (%) 
2: Minimal n (%) 
3: Mild n (%) 
.. 
Mean ±SD 
Median 
Min,Max 
 
 
Week 12 
….. 
 
 
Week 24/Early termination 
N 
1: None n (%) 
2: Minimal n (%) 
3: Mild n (%) 
.. 
Mean ±SD 
Median 
Min,Max 
 
 
 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 25 of 37 – FINAL 
 
Table 32. Skin texture change score: Descriptive and p-value by visit (ITT)  
ABPO Forte 
Vehicle 
ABPO Forte –Vehicle 
p-value (1) 
Week 12 
N 
Mean ±SD 
Median 
Min,Max 
 
 
 
 
xxxx 
Week 24/Early termination 
N 
Mean ±SD 
Median 
Min,Max 
 
 
 
 
xxxx 
 
 
 
 
Table 33. Skin texture change score: Descriptive by visit (ITT)  
 
ABPO Forte 
Vehicle 
Week 12 
N 
0: Worse n (%) 
1: No change n (%) 
2: Slight improvement n (%) 
.. 
Mean ±SD 
Median 
Min,Max 
 
 
Week 24/Early termination 
N 
0: Worse n (%) 
1: No change n (%) 
2: Slight improvement n (%) 
.. 
Mean ±SD 
Median 
Min,Max 
 
 
 
 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 26 of 37 – FINAL 
 
 
Table 34. Skin microrelief, % change from baseline: Descriptive and p-value at week 24/Early termination (ITT)  
ABPO Forte 
Vehicle 
ABPO Forte –Vehicle 
p-value (1) 
Skin microrelief: Sa (µm) 
N 
Mean ±SD 
Median 
Min,Max 
 
 
 
 
xxxx 
Skin microrelief: Smax (µm) 
… 
 
 
 
 
 
xxxx 
Skin microrelief: Sz (µm) 
… 
 
 
 
 
 
xxxx 
 
 
 
 
 
 
Table 35. Skin microrelief: Descriptive at week 24/Early termination (ITT)  
 
ABPO Forte 
Vehicle 
Total 
Skin microrelief: Sa (µm) 
N 
Mean ±SD 
Median 
Min,Max 
 
 
 
Skin microrelief: Smax (µm) 
… 
 
 
 
 
Skin microrelief: Sz (µm) 
… 
 
 
 
 
 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 27 of 37 – FINAL 
 
14.2.4. Patient-reported outcomes analyses 
 
 
Table 36. Acne scar questionnaire at baseline, Descriptive (ITT)  
 
ABPO Forte 
Vehicle 
Severity of acne 
N 
Mean ±SD 
Median 
Min,Max 
 
 
Severity of indents/holes 
N 
Mean ±SD 
Median 
Min,Max 
 
 
Face covered by indents/holes 
N 
1: Almost none n (%) 
2: A little n (%) 
3: Some n (%) 
4: A lot n (%) 
5: Almost all n (%) 
Mean ±SD 
Median 
Min,Max 
 
 
Size of indents/holes 
N 
1: Very small n (%) 
… 
5: Very large n (%) 
Mean ±SD 
Median 
Min,Max 
 
 
Quantity of indents/holes 
N 
1: Very few n (%) 
… 
5: Many n (%) 
Mean ±SD 
Median 
Min,Max 
 
 
Depth of indents/holes 
…. 
 
 
Visibility of indents/holes 
…. 
 
 
 
 
 
Table 37. Acne scar questionnaire at week 12, Descriptive (ITT)  
 
Table 38. Acne scar questionnaire at week 24/Early termination, Descriptive (ITT)  
 
 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 28 of 37 – FINAL 
 
Table 39. Acne scar questionnaire change from baseline at week 24/Early termination, Descriptive (ITT)  
 
ABPO Forte 
Vehicle 
Severity of acne: % change from baseline 
N 
Mean ±SD 
Median 
Min,Max 
 
 
Severity of indents/holes: % change from baseline 
N 
Mean ±SD 
Median 
Min,Max 
 
 
Face covered by indents/holes: change from baseline 
N 
…. 
-2: 2 grade more n (%) 
-1: 1 grade more n (%) 
 0: No change n (%) 
 1: 1 grade less n (%) 
 2: 2 grade less n (%) 
….. 
Mean ±SD 
Median 
Min,Max 
 
 
Size of indents/holes: change from baseline 
N 
…. 
-2: 2 grade more n (%) 
-1: 1 grade more n (%) 
 0: No change n (%) 
 1: 1 grade less n (%) 
 2: 2 grade less n (%) 
….. 
Mean ±SD 
Median 
Min,Max 
 
 
Quantity of indents/holes: change from baseline 
…. 
 
 
Depth of indents/holes: change from baseline 
…. 
 
 
Visibility of indents/holes: change from baseline 
…. 
 
 
 
 
 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 29 of 37 – FINAL 
 
Table 40. Subject satisfaction questionnaire at week 24/Early termination, Descriptive (ITT)  
ABPO Forte 
Vehicle 
1. How bothered were you by the treatment side effects? 
N 
Not bothered at all 
Bothered a little 
Bothered somewhat 
Bothered a great deal 
 
 
….. 
 
 
6a. Did you use the provided moisturizing lotion? 
N 
No (n,%) 
Yes (n,%) 
 
 
6b. If yes 
N 
To reduce stg/brg (n,%) 
to be adherent (n,%) 
To reduce dryness (n,%) 
pleasant to use (n,%) 
None of the above (n,%) 
 
 
 
 
 
Table 41. Subject satisfaction questionnaire at week 24/Early termination, Descriptive (ITT)  
ABPO Forte 
Vehicle 
1. How bothered were you by the treatment side effects? 
N 
Not bothered at all (n,%) 
Bothered a little (n,%) 
Bothered somewhat (n,%) 
Bothered a great deal (n,%) 
 
 
….. 
 
 
6a. Did you use the provided moisturizing lotion? 
N 
No (n,%) 
Yes (n,%) 
 
 
6b. If yes 
N 
To reduce stg/brg (n,%) 
to be adherent (n,%) 
To reduce dryness (n,%) 
pleasant to use (n,%) 
None of the above (n,%) 
 
 
 
 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 30 of 37 – FINAL 
 
Table 42. Subject questionnaire about skin cares at week 24/Early termination, Descriptive (ITT)  
Total 
1. Both skin care products were easy to incorporate into a daily routine 
N 
Strongly agree (n,%) 
Agree (n,%) 
Neither agree or disagree (n,%) 
Disagree (n,%) 
Strongly disagree (n,%) 
 
….. 
 
 
 
 
 
Table 43. Subject questionnaire about Moisturizer SPF30 at week 24/Early termination, Descriptive (ITT)  
 
 
 
 
Table 44. Subject questionnaire about Wash at week 24/Early termination, Descriptive (ITT)  
 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 31 of 37 – FINAL 
 
14.3. Safety analyses 
14.3.1. Extent of Exposure  
 
 
Table 45. Extent of exposure in days (APT) 
 
ABPO Forte 
Vehicle 
N 
Mean±SD 
Median 
Min,Max 
 
 
 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 32 of 37 – FINAL 
 
14.3.2. Adverse events  
 
Table 46. Overview of adverse events (APT) 
 
ABPO Forte treated side 
Vehicle treated side 
Unspecific treated side 
Total 
e.g. 
Event 
n 
Subject 
n (%) 
Event 
n 
Subject 
n (%) 
Event 
n 
Subject 
n (%) 
Event 
n 
Subject 
n (%) 
All AEs 
 
 
 
 
 
 
 
 
 
 
 
 
AEs related to treatment 
 
 
 
 
 
 
 
 
 
 
 
 
AEs related to procedure 
 
 
 
 
 
 
 
 
 
 
 
 
All dermatologic AEs 
 
 
 
 
 
 
 
 
 
 
 
 
Dermatologic AEs related to treatment 
 
 
 
 
 
 
 
 
 
 
 
 
Dermatologic AEs related to procedure 
 
 
 
 
 
 
 
 
 
 
 
 
All serious AEs 
 
 
 
 
 
 
 
 
 
 
 
 
Serious AEs related to treatment 
 
 
 
 
 
 
 
 
 
 
 
 
Serious AEs related to procedure 
 
 
 
 
 
 
 
 
 
 
 
 
Deaths 
 
 
 
 
 
 
 
 
 
 
 
 
All AEs leading to discontinuation 
 
 
 
 
 
 
 
 
 
 
 
 
Subjects with at least one event. Numbers in columns cannot be added because a given subject may have reported more than one AE. 
Column TOTAL is when the subject is considered as a whole 
 
 
 
 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 33 of 37 – FINAL 
 
Table 47. Frequency of all adverse events by preferred term (APT) 
ABPO Forte treated side 
Vehicle treated side 
Unspecific treated side 
e.g. 
Event 
n 
Subject 
n (%) 
Event 
n 
Subject 
n (%) 
Event 
n 
Subject 
n (%) 
Subjects with at least one event 
 
 
 
 
 
 
 
 
 
Diarrhoea nos 
 
 
 
 
 
 
 
 
 
Peptic ulcer 
 
 
 
 
 
 
 
 
 
Vomiting nos 
….. 
 
 
 
 
 
 
 
 
 
Subjects with at least one event. Numbers in columns cannot be added because a given subject may have reported more than one AE. 
 
 
Table 48. Listing of subjects with with adverse events related to procedure (APT) 
 (Include: subject number, treatment group, SOC, preferred term, date of onset, severity, serious, subject discontinued, outcome, date of resolution and relationship) 
 
 
Table 49. Frequency of all adverse events (except SAE) by preferred term (APT) 
 
 
 
Table 50. Frequency of related adverse events by preferred term (APT) 
ABPO Forte treated side 
Vehicle treated side 
e.g. 
Event 
n 
Subject 
n (%) 
Event 
n 
Subject 
n (%) 
Subjects with at least one event 
 
 
 
 
 
 
Diarrhoea nos 
 
 
 
 
 
 
Peptic ulcer 
 
 
 
 
 
 
Vomiting nos 
….. 
 
 
 
 
 
 
Subjects with at least one event. Numbers in columns cannot be added because a given subject may have reported more than one AE. 
 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 34 of 37 – FINAL 
 
 
 
 
 
Table 51: All adverse events by SOC and preferred term (APT) 
 
ABPO Forte treated side 
Vehicle treated side 
Unspecific treated side 
e.g. 
Event 
n 
Subject 
n (%) 
Event 
n 
Subject 
n (%) 
Event 
n 
Subject 
n (%) 
ANY ADVERSE EVENT 
 
 
 
 
 
 
GASTROINTESTINAL DISORDERS 
 
 
 
 
 
 
Abdominal pain nos 
 
 
 
 
 
 
….. 
 
 
 
 
 
 
IMMUNE SYSTEM DISORDERS 
 
 
 
 
 
 
Allergic sinusitis 
 
 
 
 
 
 
….. 
 
 
 
 
 
 
*Subjects with at least one event. Numbers in columns cannot be added because a given subject may have reported more than one AE. 
A subject was counted once per SOC and once per preferred term even if more than one occurrence of an event was reported within a SOC or preferred term. 
 
 
 
 
Table 52: Related adverse events by SOC and preferred term (APT) 
 
 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 35 of 37 – FINAL 
 
 
 
Table 53. Subject incidence by adverse events intensity, SOC and preferred term (APT) 
 
 
ABPO Forte treated side 
Subject n (%) 
Vehicle treated side 
Subject n (%) 
Unspecific treated side 
Subject n (%) 
e.g. 
Mild 
Moderate 
Severe 
Mild 
Moderate 
Severe 
Mild 
Moderate 
Severe 
ANY ADVERSE EVENT 
 
 
 
 
 
 
 
 
 
GASTROINTESTINAL DISORDERS 
 
 
 
 
 
 
 
 
 
Abdominal pain nos 
 
 
 
 
 
 
 
 
 
….. 
 
 
 
 
 
 
 
 
 
IMMUNE SYSTEM DISORDERS 
 
 
 
 
 
 
 
 
 
Allergic sinusitis 
 
 
 
 
 
 
 
 
 
….. 
 
 
 
 
 
 
 
 
 
Subjects with at least one event. Numbers in columns cannot be added because a given subject may have reported more than one AE. 
A subject was counted once per SOC (highest intensity whatever the AE within the SOC) and once per preferred term (highest intensity if more than one occurrence of an event is 
reported) 
 
 
 
 
 
Table 54. Subject incidence by related adverse events, SOC and preferred term (APT) 
 
 
 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 36 of 37 – FINAL 
 
 
Table 55. Serious adverse events by SOC and preferred term (APT) 
ABPO Forte treated side 
Vehicle treated side 
Unspecific treated side 
Total  
e.g. 
Event 
n 
Subject* 
n (%) 
Event 
n 
Subject* 
n (%) 
Event 
n 
Subject* 
n (%) 
Event 
n 
Subject* 
n (%) 
ANY SERIOUS ADVERSE EVENT 
 
 
 
 
 
 
 
 
GASTROINTESTINAL DISORDERS 
 
 
 
 
 
 
 
 
Abdominal pain nos 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Subjects with at least one event. Numbers in columns cannot be added because a given subject may have reported more than one AE. 
A subject was counted once per SOC and once per preferred term even if more than one occurrence of an event was reported within a SOC or preferred term. 
A listing can be provided with the information of the AE form if too few SAE. 
Table 54. Listing of subjects with serious adverse events (APT) 
(Include: subject number, treatment group, SOC, preferred term, date of onset, severity, serious, subject discontinued, outcome, date of resolution and relationship) 
 
 
 
 
 
 
 
Table 56. Summary of adverse events leading to discontinuation of study by SOC and preferred term (APT) 
ABPO Forte treated side 
Vehicle treated side 
Unspecific treated side 
Total  
e.g. 
Subject* n (%) 
Subject* n (%) 
Subject* n (%) 
Subject* n (%) 
ANY ADVERSE EVENT 
 
 
 
 
 
 
 
 
GASTROINTESTINAL DISORDERS 
 
 
 
 
 
 
 
 
Abdominal pain nos 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Subjects with at least one event. Numbers in columns cannot be added because a given subject may have reported more than one AE. 
A subject was counted once per SOC and once per preferred term even if more than one occurrence of an event was reported within a SOC or preferred term. 
A listing can be provided with the information of the AE form if too few AE leading to discontinuation of study 
Table 55. Listing of subjects with adverse events leading to discontinuation of study (APT) 
 (Include: subject number, treatment group, SOC, preferred term, date of onset, severity, serious, subject discontinued, outcome, date of resolution and relationship) 
 


GALDERMA PHASE IV 
CONFIDENTIAL 
INTERIM STATISTICAL ANALYSIS PLAN FOR RD.03.SPR.105061 
27 June 2017 
Page 37 of 37 – FINAL 
 
14.3.3. Local Tolerance  
 
 
 
Table 57. Erythema score by visit, Descriptive (APT)  
ABPO Forte 
Vehicle  
Baseline 
 
 
None 
 
 
Mild 
 
 
Moderate 
 
 
Severe 
 
 
Mean±SD 
 
 
Median 
 
 
(Min,Max) 
 
 
……. 
 
 
Week 24 
 
 
None 
 
 
Mild 
 
 
Moderate 
 
 
Severe 
 
 
Mean±SD 
 
 
Median 
 
 
(Min,Max) 
 
 
 
 
 
Table 58. Scaling score by visit, Descriptive (APT) 
 
Table 59. Dryness score by visit, Descriptive (APT)) 
 
Table 60. Stinging/Burning score by visit, Descriptive (APT)