Conditions: Acne Vulgaris
Keywords: Acne vulgaris Safety Face Trunk
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 453
Healthy volunteers: no

Brief summary:
Multi-center, open-label, non-comparative safety and efficacy study with 52 Weeks of treatment on the face and trunk for acne vulgaris.

Detailed description:
To determine the safety and efficacy of CD5789 (trifarotene) 50 µg/g cream in the long-term treatment (up to 52 Weeks) of subjects with acne vulgaris. Efficacy will be evaluated as a secondary objective.

Arms:
arm 1: None

Interventions: intervention 1: CD5789 (trifarotene)
Intervention descriptions: intervention 1: None

Protocol document:
SAP_002.pdf: 
A LONG-TERM SAFETY AND EFFICACY STUDY OF CD5789 50 μg/g CREAM IN SUBJECTS 
WITH ACNE VULGARIS
NCT Number: NCT02189629
Date: 12 Aug 2015


RD.06.SPR.18250 
Page 1 of  34 
Statistical Analysis Plan 
A LONG-TERM SAFETY AND EFFICACY STUDY OF CD5789 50 µg/g CREAM IN SUBJECTS 
WITH ACNE VULGARIS
STATISTICAL ANALYSIS PLAN 
RD.06.SPR.18250 
Version Final 
08/12/2015 
This document is electronically approved and signed by:  Biometrics Manager 


RD.06.SPR.18250 
Page 2 of  34 


RD.06.SPR.18250 
Page 3 of  34 
Document History 
Version No. 
Description of Edits 
Justification 
Date 
Amendment x 
Amendment y 


RD.06.SPR.18250 
Page 4 of  34 
TABLE OF CONTENTS 
1 
STUDY OBJECTIVES AND ENDPOINTS ........................................................................ 8 
1.1 
Study Objective (s) ............................................................................................................ 8 
1.1.1 
Primary objective (s) .................................................................................................... 8 
1.1.2 
Secondary objective (s) ................................................................................................ 8 
2 
STUDY DESIGN .................................................................................................................... 8 
3 
EFFICACY AND SAFETY ASSESSMENT ....................................................................... 9 
3.1 
Efficacy assessment ........................................................................................................... 9 
3.1.1 
IGA (Investigator’s global assessment) of facial acne .............................................. 9 
3.1.2 
PGA (Physician Global Assessment) of truncal acne.............................................. 10 
3.1.3 
Subject self-assessment of facial acne improvement ............................................... 11 
3.2 
Safety assessment ............................................................................................................ 11 
3.2.1 
Local tolerability assessment..................................................................................... 11 
3.2.2 
Adverse events ............................................................................................................ 12 
3.2.3 
Laboratory safety tests .............................................................................................. 12 
3.2.4 
Vital signs .................................................................................................................... 12 
3.2.5 
Physical examination ................................................................................................. 13 
3.3 
PK assessment (at selected sites) .................................................................................... 13 
3.4 
Other assessment ............................................................................................................. 14 
3.4.1 
Lesions counts on the face and on the trunk ........................................................... 14 


RD.06.SPR.18250 
Page 5 of  34 
3.4.2 
Photographs (at selected sites) .................................................................................. 14 
3.4.3 
Dermatology Life Quality Index (DLQI) / Children’s Dermatology Life 
Quality Index (C-DLQI) ............................................................................................ 14 
4 
EFFICACY AND SAFETY ENDPOINTS......................................................................... 15 
4.1 
Efficacy endpoints ........................................................................................................... 15 
4.2 
Safety endpoints .............................................................................................................. 15 
4.3 
PK parameters................................................................................................................. 15 
4.4 
Other endpoints ............................................................................................................... 16 
5 
POPULATIONS ANALYZED ............................................................................................ 16 
5.1 
Safety (SAF) Population ................................................................................................. 16 
5.2 
Safety (SAFT) Population on the Trunk ....................................................................... 16 
5.3 
Safety (SAFP) Population for the analysis of PGA ...................................................... 17 
6 
SAMPLE SIZE CONSIDERATION .................................................................................. 17 
7 
STATISTICAL METHODS AND DATA CONSIDERATIONS .................................... 18 
7.1 
Study subjects .................................................................................................................. 18 
7.1.1 
Disposition of subjects ............................................................................................... 18 
7.1.2 
Demographic and baseline characteristics .............................................................. 19 
7.2 
Protocol deviations .......................................................................................................... 19 
7.3 
Medical history, previous and concomitant therapies and procedures ...................... 19 
7.4 
Efficacy analysis .............................................................................................................. 20 
7.4.1 
Success rate of IGA at each time point .................................................................... 20 


RD.06.SPR.18250 
Page 6 of  34 
7.4.2 
Success rate of PGA at each time point .................................................................... 20 
7.4.3 
Grade change from baseline of IGA at each time point ......................................... 20 
7.4.4 
Grade change from baseline of PGA at each time point ........................................ 20 
7.4.5 
Subject’s assessment of facial acne improvement at each time point.................... 20 
7.4.6 
Statistical and analytical issues ................................................................................. 21 
7.4.6.1 
Handling of dropouts or missing data ..................................................................... 21 
7.4.6.2 
Interim analyses and data monitoring ..................................................................... 21 
7.4.6.3 
Examination of Subgroups...................................................................................... 21 
7.5 
Safety analysis ................................................................................................................. 22 
7.5.1 
Extent of exposure ...................................................................................................... 22 
7.5.1.1 
Study Duration ........................................................................................................ 22 
7.5.1.2 
Treatment Duration ................................................................................................. 22 
7.5.1.3 
Study Medication Usage and Treatment Compliance ............................................ 22 
7.5.2 
Cutaneous safety ........................................................................................................ 23 
7.5.3 
Adverse events ............................................................................................................ 24 
7.5.4 
Laboratory parameters ............................................................................................. 25 
7.6 
Vital Signs and Physical Exam ...................................................................................... 25 
7.7 
Pharmacokinetic Analysis .............................................................................................. 26 
7.8 
Other analyses (quality of life Questionnaire) .............................................................. 26 
7.9 
Analysis visit definition ................................................................................................... 27 


 
RD.06.SPR.18250 
 
 
 
Page 7 of  34 
 
8 
CHANGES FROM THE PROTOCOL ANALYSIS PLAN ............................................. 28 
9 
TABLE SHELLS AND REPORTING OUTPUT (GENERAL FEATURES) ................ 29 
 
 


 
RD.06.SPR.18250 
 
 
 
Page 8 of  34 
 
1 
STUDY OBJECTIVES AND ENDPOINTS 
The purpose of this statistical analysis plan (SAP) is to describe the safety, tolerability, efficacy 
and pharmacokinetic to be included in the Clinical Study Report for Protocol RD.06.SPR.18250. 
1.1 
Study Objective (s) 
1.1.1 Primary objective (s) 
The primary objective of this study is to determine the safety of CD5789 50 μg/g cream in the 
long-term treatment (up to 52 Weeks) of subjects with acne vulgaris. 
1.1.2 Secondary objective (s) 
Efficacy will be evaluated as a secondary objective. 
2 
STUDY DESIGN 
This is a multi-center, open-label, non-comparative safety and efficacy study with 52 Weeks of 
treatment on the face and trunk for acne vulgaris.  
Male and female subjects, 9 years of age or older, with an IGA of 3 and a minimum of 
20 inflammatory lesions and 25 non-inflammatory lesions on the face, with a PGA of 3 and a 
minimum of 20 inflammatory lesions and 20 non-inflammatory lesions  
on the trunk will be enrolled in the study (PGA and truncal lesions are optional inclusion criteria 
for children between 9-11 years old).  
Approximately 450 subjects will be enrolled worldwide (Europe, USA). The total number of 
sites is expected to be approximately 30 to 40 with a minimal of 10 subjects per site. 


 
RD.06.SPR.18250 
 
 
 
Page 9 of  34 
 
3 
EFFICACY AND SAFETY ASSESSMENT 
Refer to Protocol Section 7 “Clinical Trial Assessment” for details. 
3.1 
Efficacy assessment 
Efficacy will be evaluated as a secondary objective in this study. 
3.1.1 IGA (Investigator’s global assessment) of facial acne 
The areas defined for IGA assessment are forehead, each cheek, chin and nose. IGA will be 
confined to a global assessment of each area. The Investigator’s Global Assessment (IGA) is a 
snapshot static assessment.  
Investigators will evaluate the facial acne at Screening, Baseline, and at Week 12, Week 20, 
Week 26, Week 38 and Week52/ET visits or any unscheduled visit, according to the following 
scale: 
 
Investigator’s Global Assessment Scale (IGA) Face 
0 
Clear 
Clear skin with no inflammatory or non-inflammatory lesions. 
1 
Almost Clear 
A few scattered comedones and a few small papules. 
2 
Mild 
Easily recognizable; less than half the surface is involved. Some comedones and some 
papules and pustules. 
3 
Moderate 
 
More than half of the surface is involved. Many comedones, papules and pustules. One 
nodule may be present. 
4 
Severe 
 
Entire surface is involved. Covered with comedones, numerous papules and pustules. 
Few nodules may be present. 
Note: IGA assessment is to be done prior to lesion counts 


 
RD.06.SPR.18250 
 
 
 
Page 10 of  34 
 
3.1.2 PGA (Physician Global Assessment) of truncal acne 
The areas defined PGA assessment are shoulders, upper back and anterior chest which are 
accessible to self-application by the subject, i.e. the regions that the subject can easily reach and 
apply the study drug by himself or herself. PGA will be confined to a global assessment. 
The PGA is a snapshot static assessment.  
Investigators will evaluate the upper truncal acne at Screening, Baseline, and Weeks 12, 
Week 20, Week 26, Week 38 and Week 52/ET visits or any unscheduled visit, according to the 
following scale. 
Physician Global Assessment Scale (PGA) Trunk 
0 
Clear 
Clear skin with no inflammatory or non-inflammatory lesions. 
1 
Almost Clear 
A few scattered comedones and a few small papules. 
2 
Mild 
Easily recognizable; less than half the surface is involved. Some comedones and some 
papules and pustules. 
3 
Moderate 
 
More than half of the surface is involved. Many comedones, papules and pustules. One 
nodule may be present. 
4 
Severe 
 
Entire surface is involved. Covered with comedones, numerous papules and pustules. 
Few nodules may or not be present. 
 
Specific requirements for children between 9 and 11 years old who do not have moderate acne 
on the upper truncal region at Baseline (i.e. who do not have PGA of 3, at least 20 inflammatory 
lesions on the trunk and at least 20 non-inflammatory lesions on the trunk): 
 
The PGA scale will be completed at all visits (including Week 1, 2, 4 and 8 visits), and used by 
the investigators to decide if they want to start the treatment for truncal acne. However, the PGA 
data from these subjects will not be analyzed. 
 
Note: PGA assessment is to be done prior to lesion counts. 


 
RD.06.SPR.18250 
 
 
 
Page 11 of  34 
 
3.1.3 Subject self-assessment of facial acne improvement 
Subject self-assessment should occur prior any investigator assessment in order to not influence 
the subject. Subjects will evaluate his/her facial acne improvement by comparing what they 
recall on their disease at the start of the study at Weeks 12, 26 and 52/ET visits by completing 
the following scale: 
 
Subject’s Assessment of Acne Improvement  
0 
Complete Improvement 
1 
Marked Improvement 
2 
Moderate Improvement 
3 
Minimal Improvement 
4 
No Change 
5 
Worse 
3.2 
Safety assessment 
A safety assessment will be conducted for all subjects at the Screening visit (from the Informed 
consent signature) and every subsequent visit. The safety parameters are the recording of adverse 
events, laboratory safety tests, physical examination, vital signs and local tolerability scores on 
the face and on the trunk (0 [none] to 3 [severe]) for erythema, scaling, dryness, and 
stinging/burning. 
3.2.1 Local tolerability assessment 
Local tolerability (erythema, scaling, dryness, and stinging/burning) will be assessed on the face 
(forehead, each cheek, nose, chin) and trunk (upper trunk; middle and lower trunk will be 
captured if subject applied study drug on these areas) separately and will be graded separately at 
Baseline and at each post-baseline visit. Refer to protocol section 7.2.3 and 7.2.4 for more 
details. 
 
Specific requirements for children between 9 and 11 years old who do not have moderate acne 
on the trunk at Baseline (i.e. do not have PGA of 3, at least 20 inflammatory lesions on the trunk 
and at least 20 non-inflammatory lesions on the trunk): 
 
If the investigators decide to start the treatment for truncal acne in these subjects during the 
study, then the local tolerability scales (for trunk) will be completed and data will be evaluated in 
the safety analysis. 


 
RD.06.SPR.18250 
 
 
 
Page 12 of  34 
 
3.2.2 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, 
including onset/end dates of AEs, severity of AEs, relationship to the study drug, serious AEs 
and AEs of special interest. 
3.2.3 Laboratory safety tests 
The laboratory analyses will be based on Central laboratory results. The following laboratory 
safety tests will be performed at the Screening visit, Week 26 andWeek 52/ET visits. Abnormal 
laboratory results will be evaluated by the investigator as clinically significant or non-clinically 
significant. 
• Hematology: White blood cell (WBC) count with differential, red blood cell (RBC) count, 
hemoglobin(Hb), hematocrit (Hct), mean cell volume (MCV), and platelet count (Plt) 
• Blood chemistry: Creatinine, uric acid, urea nitrogen, gamma glutamyl transferase (GGT or 
γGTP), alkaline phosphatase (ALP), aspartate aminotransferase (ASAT=SGOT [AST in 
US]), alanine aminotransferase (ALAT=SGPT [ALT in US]), and bilirubin (total, direct & 
indirect). 
• Urinalysis: blood, proteins, leukocytes, glucose 
3.2.4 Vital signs 
Evaluation of vital signs will be performed after approximately 5 minutes rest in the sitting 
position at the Screening visit, Baseline visit and at Weeks 12, 26 and 52 /ET/Unscheduled visits. 
It will include measurement of systolic and diastolic blood pressure and pulse rate. 


 
RD.06.SPR.18250 
 
 
 
Page 13 of  34 
 
3.2.5 Physical examination 
The investigator should evaluate following body systems as “normal” or “abnormal” and 
should also evaluate abnormal values as “clinically significant/not clinically significant” at the 
Screening visit, Baseline visit and at Weeks 12, 26 and 52 /ET and Unscheduled visit: 
• Skin 
• Lungs 
• Abdomen 
• Eyes/ears/nose/throat 
• Neurological function 
• Musculoskeletal system 
• Lymph nodes 
• Cardiovascular system 
 
3.3 
PK assessment (at selected sites) 
In selected sites only, a PK (pharmacokinetic) assessment will be performed only in 
9 to 11 year old subjects who have agreed in the parents/guardian ICF and Assent form to have a 
PK sample taken. Systemic exposure to CD5789 will be assessed at Week 4 visit in a single 
sample PK time point. 
The following PK parameters will be determined for each subject if sufficient CD 5789 plasma 
concentrations are detectable (above the limit of quantification): 
• C 4 hours 
• Extrapolated AUC0-24h using the linear correlation between AUC0-24h and C 4 hours 


 
RD.06.SPR.18250 
 
 
 
Page 14 of  34 
 
3.4 
Other assessment 
3.4.1 Lesions counts on the face and on the trunk 
At Screening and Baseline visits, lesion counting will be performed separately on the face and on 
the upper truncal region.  
Specific requirements for children between 9 and 11 years old who do not have moderate acne 
on the trunk at Screening and/or Baseline (i.e. who do not have PGA of 3, at least 
20 inflammatory lesions on the trunk and at least 20 non-inflammatory lesions on the trunk):  
The truncal lesion counts will not be performed. 
3.4.2 Photographs (at selected sites) 
Facial and truncal photos will be taken according to a standardized procedure guideline at  
selected sites at Baseline, Week 12, Week 26 and Week 52/ET visits to document the effect 
observed on efficacy areas. 
3.4.3 Dermatology Life Quality Index (DLQI) / Children’s Dermatology Life Quality 
Index (C-DLQI) 
The Dermatology Life Quality Index (DLQI, designed for use in adults, i.e. subjects over the age 
16 years old) and Children’s Dermatology Life Quality Index (C-DLQI, designed for 16 years or 
younger at the date of Baseline visit) will be completed at Baseline and Week 12, Week 26 and 
Week 52/ET visits.   
The DLQI/ C-DLQI will measure the dermatology-related limitations of functional ability and 
the frequency, severity and impact of acne symptoms on subjects’ lives and acne-related quality 
of life.  The six areas addressed in the questionnaire are: symptoms and feelings; daily activities; 
leisure; work/school; personal relationships; and treatment.  The score on the DLQI/ C-DLQI has 
a possible range of 0 to 30 and can also be presented as a percentage of the maximum possible 
score of 30. 


 
RD.06.SPR.18250 
 
 
 
Page 15 of  34 
 
4 
EFFICACY AND SAFETY ENDPOINTS 
4.1 
Efficacy endpoints 
Efficacy endpoints include: 
1. 
Success rate of IGA (defined as 0=clear or 1=almost clear) at each time point 
2. 
Success rate of PGA (defined as 0=clear or 1=almost clear) at each time point 
3. 
Grade change from baseline of IGA at each time point 
4. 
Grade change from baseline of PGA at each time point 
5. 
Subject’s assessment of facial acne improvement at each time point 
4.2 
Safety endpoints 
Safety endpoints include: 
1. 
Local tolerability (erythema, scaling, dryness, and stinging/burning) on the face and trunk, 
2. 
Adverse event, 
3. 
Laboratory parameters 
4. 
Vital signs and physical examination 
4.3 
PK parameters  
PK(Pharmacokinetic) parameters include:  
1. 
C 4 hours 
2. 
Extrapolated AUC0-24h using the linear correlation between AUC0-24h and C 4 hours 


 
RD.06.SPR.18250 
 
 
 
Page 16 of  34 
 
4.4 
Other endpoints  
Other endpoints include: 
1. 
Dermatology Life Quality Index (DLQI) / Children’s Dermatology Life Quality 
Index(CDLQI) 
5 
POPULATIONS ANALYZED 
As this study is a long-term safety study, only the safety population will be used for all statistical 
analyses. 
The safety (SAF) population will be used for the analyses of IGA data and all safety data except 
for the local tolerability on the trunk. 
The safety population on the trunk (SAFT) will be used for the analyses of the local tolerability 
on the trunk. 
The safety population for the PGA (SAFP) will be used for the analyses of the PGA data. 
In the case that the SAFT turns out to be identical to the SAF population, then all safety analyses 
will be based on the SAF population. In the case that the SAFP turns out to be identical to the 
SAF population, then the analyses of all IGA and PGA data will be based on the SAF population. 
PK evaluable subjects in the SAF population will be used for the analysis of PK data. 
5.1 
Safety (SAF) Population 
The SAF Population is defined as subjects who applied the study drug(s) at least once. 
5.2 
Safety (SAFT) Population on the Trunk 
The SAFT population is defined as any subjects in the SAF population who also applied the 
study medication on the upper truncal region and /or on the middle and lower back at least once. 


 
RD.06.SPR.18250 
 
 
 
Page 17 of  34 
 
5.3 
Safety (SAFP) Population for the analysis of PGA 
The SAFP population is defined as any subjects in the SAF population with moderate truncal 
acne at Baseline visit. In practice, this excludes from the SAF population the children between 
9 and 11 years old who do not have PGA of 3, at least 20 inflammatory lesions on the upper 
truncal region and at least 20 non-inflammatory lesions on the upper truncal region at study 
entry. 
6 
SAMPLE SIZE CONSIDERATION 
Approximately 600 subjects will be screened to enroll 450 subjects worldwide, including the 
United States of America and Europe. 
The exposure of subjects to CD5789 50 μg/g cream follows internationally accepted guidelines 
for the assessment of clinical safety for products intended for chronic use. The International 
Conference on Harmonization E1a Guideline suggests that 300 subjects for six months or 
100 subjects for one year should be evaluated for safety. This study was designed to ensure that 
at least 300 subjects will be exposed to CD5789 50 µg/g cream for 6 months, and 100 subjects 
exposed for 1 year. 


 
RD.06.SPR.18250 
 
 
 
Page 18 of  34 
 
7 
STATISTICAL METHODS AND DATA CONSIDERATIONS 
For statistical analyses purpose, baseline is defined as the last measurement prior to the first 
application of the study drug. 
No inferential statistical analysis is planned. Data to be collected will be summarized as 
observed.  
For the summary statistics, the categorical variables will be summarized by frequency and 
percentage for each response category (N, %); and the continuous variables will be summarized 
using means, medians, minimum, maximum, and standard deviations.  
All efficacy variables, DLQI/ C-DLQI, local tolerability, laboratory tests and vital signs will be 
summarized and analyzed by analysis visit. The methodology for defining analysis visit is 
provided in Section 7.9 “Analysis visit definition”. 
SAS version 9.3 or above will be used for all statistical analyses. 
7.1 
Study subjects 
7.1.1 Disposition of subjects 
Disposition of subjects will be summarized based on SAF population. Number and percentage of 
subjects screened, enrolled, completed, discontinued, and the primary reason for discontinuation 
based on the CRF exit form will be displayed.  
In addition, the number and percentage of subjects in each study population (i.e., SAF, SAFT, 
SAFP) will be summarized. 


 
RD.06.SPR.18250 
 
 
 
Page 19 of  34 
 
7.1.2 Demographic and baseline characteristics 
The following demographics variables will be summarized for SAF population:  Age, Ethnicity, 
Race, Skin phototype, and Gender.  Age will be analyzed as a continuous variable and will be 
tabulated by age groups of “<18years” (“9-11 years”, “12-14 years”, “15-17 years”), “18-
64 years” (“18-25 years”, “26-35 years”, “36-45 years”, “46-64 years”) and “≥65 years”.  
Baseline IGA, PGA and Acne presence on back (middle/lower) will be summarized using SAF 
population. Facial lesion counts (inflammatory and non-inflammatory) will be summarized using 
SAF population and truncal lesion counts (inflammatory and non-inflammatory) will be 
summarized using SAFP population. 
7.2 
Protocol deviations 
Not applicable. 
7.3 
Medical history, previous and concomitant therapies and procedures 
For statistical analysis purposes, previous therapies/procedures are defined as those ending at or 
before the date of first dose; and concomitant therapies/procedures are defined as those ongoing 
at the date of first dose or starting after the date of first dose. 
Previous and concomitant therapies will be coded using WHODRUG dictionary.  Previous and 
concomitant procedures will be coded using MedDRA dictionary. 
A summary table will be provided for each of the following in the SAF population: 
1. 
number and percentage of subjects who had previous therapies/medications by ATC text 
and WHO drug name 
2. 
number and percentage of subjects who had concomitant therapies/medications by ATC 
text and WHO drug name 
3. 
number and percentage of subjects who had  previous procedures by System organ class 
and preferred term 
4. 
number and percentage of subjects who had concomitant procedures by System organ class 
and preferred term 


 
RD.06.SPR.18250 
 
 
 
Page 20 of  34 
 
7.4 
Efficacy analysis 
The safety population for the PGA (SAFP) will be used for the analyses of the PGA data. 
All other efficacy data will be analyzed based on the SAF population. 
7.4.1 Success rate of IGA at each time point 
A subject will be considered a success if they achieve an IGA score of ‘clear’ or ‘almost clear’.  
The success rate will be calculated as the number of successes divided by the number of subjects 
in the SAF population. The descriptive statistics will be summarized by visit.  
7.4.2 Success rate of PGA at each time point 
A subject will be considered a success if they achieve a PGA score of ‘clear’ or ‘almost clear’. 
The same summary statistics as section 7.4.1 will be provided using SAFP population.   
7.4.3 Grade change from baseline of IGA at each time point 
Raw grade at each visit and grade change from baseline at each post-baseline visit will be 
summarized as both categorical and continuous variables. In the grade change from baseline 
analysis, only subjects with both baseline and post-baseline will be included. 
7.4.4 Grade change from baseline of PGA at each time point 
The same summary statistics as section 7.4.3 will be provided using SAFP population.  
7.4.5 Subject’s assessment of facial acne improvement at each time point 
Subject’s assessment of facial acne improvement at each time point will be summarized as both 
categorical and continuous variables. 


 
RD.06.SPR.18250 
 
 
 
Page 21 of  34 
 
7.4.6 Statistical and analytical issues 
7.4.6.1 Handling of dropouts or missing data 
In this study, summary statistics will be based on the observed data and no missing data 
imputation will be performed. 
7.4.6.2 Interim analyses and data monitoring 
No interim analysis is planned for this study. 
7.4.6.3 Examination of Subgroups 
Subgroup summaries will be provided by descriptive statistics for success rate of IGA (using 
SAF) and PGA (using SAFP), within each category of the following classification variables: 
• Age 
Group 
[<18 
years 
(“9-11 
years”, 
“12-14 
years”, 
“15-17 years”), 
18-64 years(“18-25 years”, “26-35 years”, “36-45 years”, “46-64 years”) and ≥65 years”)] 
• Gender (female, male) 
• Race (white, non-white) 
• Country (Europe, USA) 
• Skin Phototype (I-III, IV-VI) 


 
RD.06.SPR.18250 
 
 
 
Page 22 of  34 
 
7.5 
Safety analysis 
All safety data will be analyzed based on the SAF population except for the local tolerability on 
the trunk. The SAFT population will be used for the analyses of the local tolerability on the 
trunk. 
7.5.1 Extent of exposure 
7.5.1.1 Study Duration 
Study duration (day) is defined as the date of the last visit minus the date of the baseline visit 
plus one. Study duration will be summarized by descriptive statistics. 
7.5.1.2 Treatment Duration  
Treatment duration (day) is defined as “the date of the last application on face or the trunk, 
whichever is later, minus the date of the first application on face or the trunk, whichever is 
earlier, plus one”.  If the date of the last application is not available, the date of the last visit will 
be used in calculation. If the date of the first application is not available, the date of the Baseline 
visit will be used in calculation. 
Treatment duration will be summarized by descriptive statistics.  
7.5.1.3 Study Medication Usage and Treatment Compliance  
The study medication usage will be assessed based on CRF data in terms of the number of 
applications applied.  
Number of applications applied is calculated as the expected number of applications minus the 
total number of missed applications during the treatment. If the number of missed applications is 
unknown, then 50% doses will be assumed to be missed between two adjacent visits. 
The expected number of applications is defined as the planned total number of applications 
during the exposed period. Number of applications applied and the daily average applications 
applied will be summarized. 
Treatment compliance (%) is defined as (the Number of applications applied over the expected 
number of applications) *100%. 


 
RD.06.SPR.18250 
 
 
 
Page 23 of  34 
 
Study medication usage based on number of applications may also be summarized for the face 
using SAF population and for the trunk using the SAFT population separately. 
Additionally, the study medication usage will be assessed based on the returned tubes. Total 
medication usage weight (g) and daily medication weight (g/day) will be calculated for each 
subject and be summarized by descriptive statistics.  
Total medication usage (g) = total dispensed weight (g) - total returned weight (g); 
Daily medication usage (g/day) = total medication usage (g) / study duration (day).  
The tubes that were dispensed but not returned will be considered no information and will not be 
included in the calculation. If all dispensing tubes for a subject are not returned, the subject’s 
total returned weight and daily medication usage will be considered missing. 
7.5.2 Cutaneous safety 
Analyses of the local tolerability on the face will be based on SAF population; and the analyses 
of the local tolerability on the trunk will be based on SAFT population. 
Local tolerability variables (erythema, scaling, dryness, stinging/burning) will be summarized at 
Baseline, each post-baseline visit, “Worst” score, and “Final” score. “Worst” score is the highest 
severity score observed during post-baseline period for a subject. “Final” score is the last data 
observed during the post-baseline period for a subject. In addition, the number and percentage of 
subjects with a local tolerability score worsened from baseline will be summarized descriptively 
at each post-baseline visit, “Final” scores, and “Worst” score.  
Additionally, subjects with a local tolerability score worse than the Baseline score will be 
summarized graphically at each post-Baseline visit including “Final” scores and “Worst” score.  
Summary statistics by treating the severity scale as continuous outcome will also be presented. 
Subgroup analyses by Age Group (<18 years, >=18 years), Race (white, non-white), Gender 
(female, male), Country (Europe, USA), and Skin Phototype (I-III, IV-VI) will be provided. 


 
RD.06.SPR.18250 
 
 
 
Page 24 of  34 
 
7.5.3 Adverse events 
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred on or 
after the first study drug application. 
TEAEs will be tabulated in frequency tables by System Organ Class (SOC) and Preferred Term 
(PT) based on the MedDRA dictionary. In addition, incidence of TEAE by quarter will be 
summarized for “Baseline to < Month 3” (1 to 89 days), “Month 3 to <Month 6” (90 to179 days), 
“Month 6 to < Month 9” (180 to 269 days), “Month 9 to 1 Year” (≥270 days). The AE incidence 
for each time period will be calculated by the number of subjects with AE onset dates within 
each period divided by the number of subjects at risk at the start of each period. Additional 
summary tables and listings will be provided for adverse events that are considered serious 
(SAEs), related to the study drug, severe, leading to discontinuation and of special interest. For a 
given TEAE, a subject will be counted once even if he or she has experienced multiple episodes 
for that particular TEAE.  
The AEs of Special Interest for this protocol are pre-defined as follows: 
• Out-of-range laboratory results that are identified as clinically significant and related to the 
study drug(s) are AESIs. 
• Related cutaneous AEs which lead to permanent treatment discontinuation. 
• Suspicion of allergic reaction suspected to be related to the study drug. 
The following TEAE summaries will be provided: 
• Summary of overall AE(s) 
• Frequency and percentage of subjects with AE(s) by System Organ Class (SOC) and 
Preferred Term (PT) 
• Frequency and percentage of subjects with serious AE(s) by System Organ Class (SOC) 
and Preferred Term (PT)  
• Frequency and percentage of subjects with related AE(s) by System Organ Class (SOC) 
and Preferred Term (PT)  
• Frequency and percentage of subjects with related AE(s) by Preferred Term (PT)  
• Frequency and percentage of subjects with AE(s) leading to discontinuation by System 
Organ Class (SOC) and Preferred Term (PT)  
• Frequency and percentage of subjects with severe AE(s) by System Organ Class (SOC) 
and Preferred Term (PT)  
• Frequency and percentage of subjects with AE(s) of special interest by System Organ Class 
(SOC) and Preferred Term (PT)  


RD.06.SPR.18250 
Page 25 of  34 
Summaries of overall Adverse Events and summaries of Adverse Events by System Organ Class 
(SOC) and Preferred Term (PT) will be presented by Age Group (<18 years, ≥18 years), 
Race (white, non-white), Gender (female, male), Country (Europe, USA) and Skin 
Phototype (I-III, IV-VI).  
Furthermore, the chronology of TEAE will be assessed with respect to AE onset and 
AE duration. Descriptive statistics (N, minimum, medians and maximum) will be presented by 
Preferred Term for the following:   
•
Duration from the first dose date to AE onset date,
•
Duration of AE from AE start date to AE stop date.
7.5.4 Laboratory parameters 
The descriptive statistics for laboratory data collected at each visit and changes from Baseline 
will be provided. 
A summary table of the categorical grade shift changes using the normal ranges from baseline to 
the last post-baseline visit will be presented for each laboratory parameter. Only SAF subjects 
with both baseline and post-baseline assessments will be included in this analysis. 
For each laboratory test, a complete data listing will be provided for subjects who have any 
laboratory results outside the reference ranges, and for subjects who have any laboratory results 
with clinical significance. 
7.6 
Vital Signs and Physical Exam 
The descriptive statistics for Vital Signs collected at each visit and changes from Baseline will be 
provided. Nominal eCRF visit will be used as analysis visit. 
Physical exam will be provided in a subject-by-subject listing. 


 
RD.06.SPR.18250 
 
 
 
Page 26 of  34 
 
7.7 
Pharmacokinetic Analysis  
Quantifiable PK profiles of CD5789 from previous PK studies 18237 and 40182 were used to 
investigate the relationship between AUC0-24h and selected plasma points. A strong correlation 
was found between AUC0-24h and C4h using linear regression. The extrapolated AUC0-24h will 
be calculated using the following equation. For more details, refer to the document CD5789 
Limited sampling strategy for estimation of the AUC0-24h in the 9 to 11 years old subjects.   
AUC0-24h =34.26 + 7.90* C4h 
The PK parameters C4h and extrapolated AUC0-24h will be summarized by descriptive statistics. 
Coefficient of variation (CV), geometric mean (GEO Mean), geometric standard deviation 
(GEO SD) and geometric coefficient of variation (GEO CV) will be presented as well.  
For C4h, the BLQ (below limit of quantification) values will be imputed using the LOQ (limit of 
quantification: 5pg/mL). Summaries with imputation and with no imputation will be both 
provided. 
7.8 
Other analyses (quality of life Questionnaire) 
The DLQI/ C-DLQI will be summarized descriptively. Only SAF subjects with both baseline and 
post-baseline visit assessments using the same age-appropriate questionnaire will be included in 
the analyses. 
Total Scores and Change from Baseline at Week 12, 26, and 52/Early Termination for DLQI/C-
DLQI, DLQI only, and C-DLQI only will be summarized.  In addition, number and percent of 
subjects will be reported for each of the following categories of the effect of disease on the 
quality of life as specified in Table 1: 
Table 1 
DLQI/C-DLQI Categories 
DLQI 
C-DLQI 
DLQI Category 
Range of Total Score C-DLQI Category 
Score Maximum 
No effect 
0 - 1 
No effect 
0 - 1 
Small effect 
2 - 5 
Small effect 
2 - 6 
Moderate effect 
6 - 10 
Moderate effect 
7 – 12 
Very large effect 
11 – 20 
Very large effect 
13 – 18 
Extremely large effect 
21 - 30 
Extremely large effect 
19 - 30 
 


 
RD.06.SPR.18250 
 
 
 
Page 27 of  34 
 
Summaries of DLQI only and C-DLQI only by each dimension as defined in Table 2 below will 
also be provided.  
Table 2 
DLQI/C-DLQI Dimensions 
DLQI 
C-DLQI 
DLQI dimensions 
Score Maximum 
C-DLQI dimensions 
Score Maximum 
Total Score 
30 
Total Score 
30 
Symptoms and feelings 
6 
Symptoms and feelings 
6 
Daily Activities 
6 
Sleep 
3 
Leisure 
6 
Leisure 
9 
Work and School 
3 
School or holidays 
3 
Personal relationships 
6 
Personal relationships 
6 
Treatment 
3 
Treatment 
333 
7.9 
Analysis visit definition 
For efficacy, DLQI/ C-DLQI and local tolerability data, analysis visit will be assigned according 
to the algorithm in Table 3 below to summarize the data by proper visit window interval. 
Study day is calculated as visit date minus the date of first application plus 1. If multiple 
measurements are taken in the same interval, the one closest to the target study day will be used 
for the analysis. If two measurements are taken with equal differences in timing compared with 
the target date, the nominal visit number (recorded on the CRF page) will be used. If there is 
missing measurement at Baseline, Screening data will be used to impute the missing baseline 
data, i.e. Baseline will be the last available data prior to first application of study drug.  
Table 3 
Analysis Visit and Visit Window 
Analysis Visit 
Analysis Visit Number in 
Derived Dataset 
Target Study Day 
Visit Window 
(Study Day) 
Baseline 
1 
1 
[ ≤1 ] 
Week 1 
2 
8 
[ 2 – 11 ] 
Week 2 
3 
15 
[ 12 – 21 ] 
Week 4 
4 
29 
[ 22 – 42 ] 
Week 8 
5 
57 
[ 43 – 70 ] 
Week 12 
6 
85 
[ 71 – 112 ] 
Week 20 
7 
141 
[ 113 – 161 ] 
Week 26 
8 
183 
[ 162 – 224 ] 
Week 38 
9 
267 
[ 225 – 315 ] 
Week 52 
10 
365 
    > 315or more] 
 


 
RD.06.SPR.18250 
 
 
 
Page 28 of  34 
 
When assigning the analysis visits for vital signs, no visit window will be applied; Nominal 
eCRF visit will be used as analysis visit for summaries. Only data from schedule visit will be 
summarized. 
When assigning the analysis visits for laboratory data, no visit window will be applied, however, 
the following rules will be applied: 
1. 
If sample date is at or prior to date of first application, the data will be considered as 
screening visit. If multiple measurements of screening due to rescreening, retest or other 
unexpected reasons, the data closest to date of first application will be chosen. 
2. 
Lab data from scheduled visit will be considered first when assigning analysis visit of each 
scheduled visit. If there is no data from scheduled visit available, the last of those 
corresponding unscheduled visit will be considered for assignment of analysis visits. 
3. 
When assigning Final visit, the lab data from the last post-baseline scheduled visit during 
treatment period will be considered first. If the last scheduled visit during treatment period 
have missing lab data due to any reason and there are subsequent unscheduled lab data 
available, the last of those corresponding unscheduled lab data will be assigned as Final 
visit. Otherwise, the previous visit lab data will be considered in the same manner.  
8 
CHANGES FROM THE PROTOCOL ANALYSIS PLAN 
There are no changes from the planned analyses on Protocol. 


 
RD.06.SPR.18250 
 
 
 
Page 29 of  34 
 
9 
TABLE SHELLS AND REPORTING OUTPUT (GENERAL FEATURES) 
The tentative list of tables to be produced in the reporting of this study is shown below.  All 
eCRF data will also be available as subject listings and the eCRF data will be available in 
CDISC compliant data set. 
Demographic and Baseline Characteristics tables   
• Summary of Subject Enrollment 
• Summary of Subject Enrollment by Analysis Center/Site, SAF Population 
• Summary of Subject Disposition, SAF Population 
• Summary of Subject Disposition by Analysis Center/Site, SAF Population 
• Summary of Subject Disposition by Study Duration, SAF Population 
• Listing of Discontinued Subjects, SAF Population 
• Summary of Subject Demographics and Baseline Characteristics, SAF Population 
• ATC Class, WHO Drug and Drug Name, SAF Population 
• Summary of Previous Therapy, SAF Population 
• Summary of Concomitant Therapy, SAF Population 
• System Organ Class, Preferred Term and Procedure/Non-drug Therapy, SAF Populations 
• Summary of Previous Procedure / Non-Drug Therapy, SAF Population 
• Summary of Concomitant Procedure/Non-drug Therapy, SAF Population 
 
Efficacy tables   
 
• Summary of Success Rate of Investigator’s Global Assessment, SAF Population 
• Summary of Success Rate of Physician Global Assessment, SAFP Population 
• Summary of Investigator’s Global Assessment, SAF Population 
• Summary of Physician Global Assessment, SAFP Population 
• Summary of Subject Self-Assessment of Acne, SAF Population 
• Summary of Dermatology Life Quality Index (DLQI) Total Score, SAF Population 
• Summary of Children Dermatology Life Quality Index (CDLQI) Total Score, SAF 
Population 
• Summary of Dermatology Life Quality Index (Adult and Child) Total Score, SAF 
Population 
• Summary of Dermatology Life Quality Index (DLQI) by Dimension, SAF Population 


 
RD.06.SPR.18250 
 
 
 
Page 30 of  34 
 
• Summary of Children Dermatology Life Quality Index (CDLQI), SAF Population 
• Summary of Success Rate of Investigator’s Global Assessment by Gender, SAF Population 
• Summary of Success Rate of Investigator’s Global Assessment by Race, SAF Population 
• Summary of Success Rate of Investigator’s Global Assessment by Age, SAF Population 
• Summary of Success Rate of Investigator’s Global Assessment by Country, SAF 
Population 
• Summary of Success Rate of Investigator’s Global Assessment by Skin Phototype, SAF 
Population 
• Summary of Success Rate of Physician Global Assessment by Gender, SAFP Population 
• Summary of Success Rate of Physician Global Assessment by Race, SAFP Population 
• Summary of Success Rate of Physician Global Assessment by Age, SAFP Population 
• Summary of Success Rate of Physician Global Assessment by Country, SAFP Population 
• Summary of Success Rate of Physician Global Assessment by Skin Phototype, SAFP 
Population 
 
Safety tables 
• Summary of Study duration, SAF Population  
• Summary of Treatment duration, SAF Population 
• Summary of Study Medication Usage and Compliance, SAF Population 
• System Organ Class (SOC), Preferred Term (PT) and AE Diagnosis, SAF Population 
• Summary of Overall Adverse Events, SAF Population 
• Summary of Adverse Events by System Organ Class and Preferred Term, SAF Population 
• Summary of Adverse Events by Preferred Term, SAF Population 
• Summary of Serious Adverse Events by System Organ Class and Preferred Term, SAF 
Population 
• Listing of Serious Adverse Events, SAF Population 
• Summary of Adverse Events Leading to Discontinuation by System Organ Class and 
Preferred Term, SAF Population 
• Listing of Adverse Events Leading to Discontinuation, SAF Population 
• Summary of Adverse Events Related to Study Drug by System Organ Class and Preferred 
Term, SAF Population 
• Summary of Adverse Events Related to Study Drug by Preferred Term, SAF Population 
• Listing of Adverse Events Related to Study Drug, SAF Population 


 
RD.06.SPR.18250 
 
 
 
Page 31 of  34 
 
• Summary of Severe Adverse Events by System Organ Class and Preferred Term, SAF 
Population 
• Listing of Severe Adverse Events, SAF Population 
• Summary of Adverse Events of Special Interest by System Organ Class and Preferred 
Term, SAF Population 
• Listing of Adverse Events of Special Interest, SAF Population 
• Listing of Subjects with Positive Urine Pregnancy Test Results, SAF Population 
• Summary of Vital Signs and Physical Examinations, SAF Population 
• Summary of Overall Adverse Events by Gender, SAF Population 
• Summary of Overall Adverse Events by Race, SAF Population 
• Summary of Overall Adverse Events by Age, SAF Population 
• Summary of Overall Adverse Events by Country, SAF Population 
• Summary of Overall Adverse Events by Skin Phototype, SAF Population 
• Summary of Adverse Events by System Organ Class and Preferred Term by Gender, SAF 
Population 
• Summary of Adverse Events by System Organ Class and Preferred Term by Race, SAF 
Population 
• Summary of Adverse Events by System Organ Class and Preferred Term by Age, SAF 
Population 
• Summary of Adverse Events by System Organ Class and Preferred Term by Country, SAF 
Population 
• Summary of Adverse Events by System Organ Class and Preferred Term by Skin 
Phototype, SAF Population 
• Summary of chronology of Adverse Events, SAF Population 
• Summary of Erythema on the Face, SAF Population 
• Summary of Scaling on the Face, SAF Population 
• Summary of Dryness on the Face, SAF Population 
• Summary of Stinging/Burning on the Face, SAF Population 
• Summary of Erythema on the Trunk, SAFT Population 
• Summary of Scaling on the Trunk, SAFT Population 
• Summary of Dryness on the Trunk, SAFT Population 
• Summary of Stinging/Burning on the Trunk, SAFT Population 
• Summary of Erythema Worse than Baseline on the Face, SAF Population 


RD.06.SPR.18250 
Page 32 of  34 
•
Summary of Scaling Worse than Baseline on the Face, SAF Population
•
Summary of Dryness Worse than Baseline on the Face, SAF Population
•
Summary of Stinging/Burning Worse than Baseline on the Face, SAF Population
•
Summary of Erythema Worse than Baseline on the Trunk, SAFT Population
•
Summary of Scaling Worse than Baseline on the Trunk, SAFT Population
•
Summary of Dryness Worse than Baseline on the Trunk, SAFT Population
•
Summary of Stinging/Burning Worse than Baseline on the Trunk, SAFT Population
•
Summary of Erythema Worse than Baseline on the Face by Gender, SAF Population
•
Summary of Scaling Worse than Baseline on the Face by Race, SAF Population
•
Summary of Dryness Worse than Baseline on the Face by Age, SAF Population
•
Summary of Stinging/Burning Worse than Baseline on the Face by Country, SAF
Population
•
Summary of Erythema Worse than Baseline on the Trunk by Gender, SAFT Population
•
Summary of Scaling Worse than Baseline on the Trunk by Race, SAFT Population
•
Summary of Dryness Worse than Baseline on the Trunk by Age, SAFT Population
•
Summary of Stinging/Burning Worse than Baseline on the Trunk by Country, SAFT
Population
•
Listing of Central Laboratory Data Normal Ranges
•
Summary of Laboratory Data - Hematology, SAF Population
•
Summary of Laboratory Data - Blood Chemistry, SAF Population
•
Summary of Laboratory Data - Urine Drug Screen, SAF Population
•
Shift table of Laboratory Data from Baseline to last visit - Hematology, SAF Population
•
Shift table of Laboratory Data from Baseline to last visit - Blood Chemistry, SAF
Population
•
Shift table of Laboratory Data from Baseline to last visit - Urine Drug Screen, SAF
Population
•
Listing of subjects with Laboratory Data Out of Reference Range, SAF Population
•
Listing of subjects with Clinical Significant Laboratory Data, SAF Population
•
Listing of subjects with Positive Urine Pregnancy Test Results, SAF Population


 
RD.06.SPR.18250 
 
 
 
Page 33 of  34 
 
Pharmacokinetic tables 
• Listing of Individual Subject Plasma Concentration and Pharmacokinetic Parameters, SAF 
Population PK evaluable subjects  
• Summary of Plasma Concentration and Pharmacokinetic Parameters (with imputation and 
without imputation), SAF Population PK evaluable subjects 
 
Figures 
• Success Rate of Investigator’s Global Assessment, SAF Population 
• Success Rate of Physician Global Assessment, SAF Population 
• Erythema Worse than Baseline on the Face, SAF Population 
• Scaling Worse than Baseline on the Face, SAF Population 
• Dryness Worse than Baseline on the Face, SAF Population 
• Stinging/Burning Worse than Baseline on the Face, SAF Population 
• Erythema Worse than Baseline on the Trunk, SAFT Population 
• Scaling Worse than Baseline on the Trunk, SAFT Population 
• Dryness Worse than Baseline on the Trunk, SAFT Population 
• Stinging/Burning Worse than Baseline on the Trunk, SAFT Population 
 
Subject data listings 
• Prematurely Discontinued Subjects 
• Completed Subjects 
• Screen Failed Subjects 
• Subject Randomization 
• Demographics and Baseline Characteristics 
• Inclusion/Exclusion Criteria Not Met 
• Medical History 
• Therapy 
• Procedure/Non-Drug Therapy 
• General Comments 
• Study Medication Compliance 
• Study Medication Usage 
• Investigator’s Global Assessment, Physician Global Assessment, Lesion Counts and 
Subject Self-Assessment of Acne 


RD.06.SPR.18250 
Page 34 of  34 
•
Success of Investigator’s Global Assessment and Physician Global Assessment (Derived
Efficacy Variables)
•
Children’s Dermatology Life Quality Index Score
•
Local Tolerability Assessment
•
Adverse Events
•
Adverse Event Comments
•
Vital Signs
•
Physical Examinations
•
Pregnancy Test

Prot_000.pdf: 
GALDERMA R&D 
Protocol Summary 
RD.06.SPR.18250 – 07 Aug 2014  
Page 1 of 13 
 
Study title:  
A long-term safety and efficacy study of CD5789 50µg/g cream in subjects with acne vulgaris 
 
Short Title:  
CD5789 Long Term Study (LTS) on acne vulgaris 
 
Study Phase: 
Phase 3 
 
Eudract Number:  
2014-001755-23 
 
IND Number: 
111091 
 
Treatment Indication: 
Topical treatment of moderate (IGA/PGA score 3) acne vulgaris 
 
Study Population 
Subjects age 9+ years old, male and female 
 
Background and Rationale: 
Acne vulgaris is the most common skin disease, affecting almost 80 percent of the population at 
some time between the ages of 11 and 30 years. It can persist for years and result in 
disfigurement and permanent scarring, and may have serious adverse effects on psychosocial 
development, resulting in emotional problems, withdrawal from society, and depression. 
Truncal (back and chest) acne has been estimated to occur in over half the number of acne 
patients even if facial acne is the most common and often the most visible form of acne. In one 
study of patients referred to a dermatology clinic revealed that more than 60 percent of 
individuals had back acne. In another cohort of 696 patients from five cities, half of patients with 
facial acne were found to have coexistent truncal involvement. 
Acne is a multifactorial inflammatory disease affecting pilosebaceous follicles.  
Both clinically and pathophysiologically, truncal acne and facial acne are similar in terms of 
specific lesions (eg closed comedones, open comedones, papules and pustules etc.). Further, the 
management of truncal acne vulgaris warrants an approach similar to what is used for the 
treatment of facial acne.  
Several Proof of Concept studies have shown that CD5789 formulated in gel and creams at 
various concentrations (25, 50 and 100 µg/g) was effective in reducing inflammatory, non-
inflammatory and thus total lesion counts within 4 to 8 weeks of topical treatment in subjects 


GALDERMA R&D 
Protocol Summary 
RD.06.SPR.18250 – 07 Aug 2014  
Page 2 of 13 
 
with moderate acne vulgaris of the face in comparison to its placebo. This was confirmed by 
investigators’ and subjects’ assessments. 
A recent Phase 2 study evaluated three doses of CD5789 cream (25 µg/g, 50 µg/g, and 100 µg/g) 
in subjects with moderate and severe acne. The study concluded that CD5789 at 25 µg/g 
represents the minimally effective dose. CD5789 50 µg/g, and 100 µg/g were both determined to 
be efficacious with only a modest efficacy advantage in favor of the higher dose.  
For safety, a dose response trend was observed in the overall summary of adverse events (AEs), 
with CD5789 100µg/g reporting the highest event rate of any adverse event, related adverse 
events, related adverse events leading to study withdrawal. Overall and for all categories of AEs, 
CD5789 50 µg/g had an AE profile that was comparable to vehicle control and notably better 
than CD5789 100 µg/g. The superior safety and local tolerability profile of CD5789 50 µg/g 
cream led to the choice of this dose for carrying forward to Phase 3 in this indication. 
The local tolerability profile of CD5789 was also dose dependent and followed the usual pattern 
whereby mean scores peaked at week 1 and gradually decreased over the succeeding weeks. In 
comparative terms, CD5789 50 µg/g was generally better tolerated than tazarotene 1% gel for 
most of the parameters assessed, whereas CD5789 100 µg/g was either comparable or less well 
tolerated than tazarotene 1% gel. 
Although both doses of 50 µg/g and 100 µg/g of CD5789 provide a positive benefit risk ratio in 
the treatment of acne vulgaris, the superior safety and local tolerability profile of CD5789 
50 µg/g cream argues in favour of carrying forwards this dose in Phase 3. 
 
Study Objectives  
This study objectives are to determine the safety and efficacy of CD5789 50µg/g cream in the 
long-term treatment (up to 52 Weeks) of subjects with acne vulgaris. Efficacy will be evaluated 
as a secondary objective. 
 
Study Design 
Multi-center, open-label, non-comparative safety and efficacy study with up to 52 Weeks of 
treatment on the face and trunk for acne vulgaris.  
From Baseline to Week 12 visits, subjects will apply the study drugs once daily in the evening to 
the Face and to the Trunk (except for children between 9 and 11 years old who do not have 
moderate acne on the trunk at Baseline, it is up to the investigators to decide if these 9 to 11 
years old subjects should be treated or not for truncal acne). 
 


GALDERMA R&D 
Protocol Summary 
RD.06.SPR.18250 – 07 Aug 2014  
Page 3 of 13 
 
From Week 12 to Week 52/ET visits, subject will apply the study drug according to the IGA and 
PGA assessment as follow:  
 
IGA 
Facial acne  
PGA 
Truncal acne 
Study Treatment regimen 
0 
0 
Stop on the Face  
Stop on the Trunk 
At least 1 
0 
Stop on the Trunk 
Continue on the Face 
0 
At least 1 
Stop on the Face 
Continue on the Trunk 
At least 1 
At least 1 
Continue on the Face 
Continue on the Trunk  
 
Specific requirements for children between 9 and 11 years old who do not have moderate acne 
on the trunk at Baseline (i.e. who do not have PGA of 3, at least 20 inflammatory lesions on the 
trunk and at least 20 non-inflammatory lesions on the trunk): 
In this case, it is up to the investigators to decide if these 9 to 11 years old subjects should be 
treated or not for truncal acne. In these subjects, treatment can be started (based on investigator’s 
decision) even if e.g. PGA=1, or the subject has less than 20 inflammatory lesions on the trunk 
and/or less than 20 non-inflammatory lesions on the trunk). These subjects will not be assessed 
for efficacy, but they will be assessed for safety and local tolerability. 
In any case the subject should continue in the study until the Week 52 visit. 
Unscheduled visit maybe carried-out if the subject experiences an acne flare or a local 
tolerability issue that may need to reintroduce or to adapt the study treatment regimen. 
 
Total Number of Sites 
The total number of sites is expected to be 33 to 47 approximately. 
 
Region / Countries 
The study will be conducted in Europe, Japan and USA. 
 
Study Duration  
The planned clinical trial duration, from First Subject In (FSI) to Last Subject Out (LSO) is 
approximately 24 months.  
The planned duration of recruitment, from FSI to Last Subject In (LSI), is approximately to 6 to 
12 months. 


GALDERMA R&D 
Protocol Summary 
RD.06.SPR.18250 – 07 Aug 2014  
Page 4 of 13 
 
 
Duration of Subject Participation  
Clinical trial participation for each subject is approximately 12 months (up to 54 weeks +/- 3 
days including a screening period of up to 2 weeks). 
 
Total Number of Subjects 
Approximately 665 subjects will be screened to enrol 500 subjects worldwide (Europe, USA and 
Japan), including approximately 50 Japanese subjects.  
Treatment Duration 
Each subject will be treated for up to 52 weeks.   
Inclusion Criteria 
In order to be eligible for the study, subjects must fulfill all of the following criteria: 
 
1. Male or female, 9 years of age and older at Screening visit. 
2. The subject has a facial acne severity grade of IGA 3 (moderate) at Screening and 
Baseline visits.  
3. The subject has a minimum of 20 inflammatory lesions and 25 non-inflammatory lesions 
on the face at Screening and Baseline visits.  
4. The subject has truncal acne severity grade of PGA 3 (moderate) at Screening and 
Baseline visits on the shoulders, anterior chest and upper back reachable to self-
application of study drug by the subject (this inclusion criterion is optional for children 
between 9 and 11 years old). 
5. The subject has a minimum of 20 inflammatory lesions and 20 non-inflammatory lesions 
at Screening and Baseline visits on the shoulders, upper back and anterior chest (this 
inclusion criterion is optional for children between 9 and 11 years old). 
6. Female of non-childbearing potential pre-menarcheal or postmenopausal (absence of 
menstrual bleeding for 1 year prior to Screening, without any other medical reason), 
hysterectomy or bilateral oophorectomy. 
7. Female of childbearing potential:  
a. With a negative urine pregnancy test (UPT) at Screening and Baseline visits,  
b. Who has been strictly abstinent for 1 month prior to Baseline and agrees to 
continue for the duration of the clinical trial and at least 1 month after the last 
study drug application, 
OR 
c. Who agrees to use an effective and approved contraceptive method(s) for the 
duration of the study and at least 1 month after the last study drug application. An 
effective method of contraception is defined as: 
i. bilateral tubal ligation;  


GALDERMA R&D 
Protocol Summary 
RD.06.SPR.18250 – 07 Aug 2014  
Page 5 of 13 
 
ii. combined oral contraceptives (estrogens and progesterone) or implanted or 
injectable contraceptives or hormonal contraceptive vaginal rings with a 
stable dose for at least 1 month prior to the Baseline visit; 
iii. hormonal intra-uterine device (IUD) inserted at least 1 month prior to the 
Baseline visit; 
iv. vasectomized partner for at least 3 months prior to the Baseline visit. 
8. Female of childbearing potential uses combined oral contraceptives approved as acne 
treatment (e.g., Ortho Tri-Cyclen®, Yaz®, Diane-35®), the dose should be stable for at 
least 6 months prior to the Baseline visit. 
9. For pre-menstrual female who begin menses during the study:  
a. Who agrees to be strictly abstinent for the duration of the clinical trial and at least 
1 month after the last study drug application,  
OR 
b. Who agrees to use an effective and approved contraceptive method(s) for the 
duration of the study and at least 1 month after the last study drug application and 
agrees to undergo pregnancy tests. An effective method of contraception is 
defined as combined oral contraceptives (oestrogens and progesterone) or 
implanted or injectable contraceptives, or hormonal  intra-uterine device (IUD) or 
hormonal contraceptive vaginal rings.  
10. The Subject is willing and is able to comply with all of the time commitments and 
procedural requirements of the protocol (for subjects who are minors, the parent(s)/legal 
representative must be also willing and able to comply with study requirements). 
11. The subject agrees to participate in the study, verified by dating and signing an approved 
written Informed Consent Form (ICF) or, for subjects under age of majority, an assent 
form signed by the subject in conjunction with an ICF signed by the parent(s)/legal 
representative at the Screening visit before any study procedures.  
In selected sites (outside Japan): Child between 9 and 11 years old and the parent(s)/legal 
representative agrees to participate in PK assessment, will accept the PK procedure in the 
Consent / Assent form. Participation to PK sampling is not mandatory to participate in the 
Study. 
In selected sites: The subject agrees to participate to the study photographs, verified by 
dating and signing a separate approved written Informed Consent Form for photos and for 
subjects under age of majority, an assent form signed by the subject in conjunction with 
an photo ICF signed by the parent(s)/legal representative at the Screening visit.  
Participation to photo procedures is not mandatory to participate in the Study. 
12. In USA centers only: Apprised of the Health Insurance Portability and Accountability 
Act (HIPAA) and is willing to share personal information and data, as verified by signing 
a written authorization at the Screening visit. 
 
Exclusion Criteria 
Any subjects who meet one or more of the following exclusion criteria will not be eligible for 
this study. 


GALDERMA R&D 
Protocol Summary 
RD.06.SPR.18250 – 07 Aug 2014  
Page 6 of 13 
 
1. The Subjects with severe forms of acne (acne conglobata, acne fulminans) or secondary 
acne form (chloracne, drug-induced acne, etc.).  
2. The Subject has more than 1 nodule on the face at Screening or Baseline. 
3. The subject has more than 1 nodule on the trunk at Screening or Baseline. 
4. The Subject has any acne cyst on the face at Screening and at Baseline visits. 
5. The Subject has any acne cyst on the trunk at Screening and at Baseline visits. 
6. The Subject has a beard or facial/body hair that may interfere with the study assessments. 
7. The Subject with tattoos on the face, the shoulders, upper back and anterior chest on 
evaluable area that may interfere with the study assessments or subject who intend to 
have tattoos on these areas during the course of the study. 
8. The Subjects has any uncontrolled or serious disease or any medical or surgical condition 
that may either interfere with the interpretation of the trial results and/or put the subject at 
significant risk (according to the Investigator’s judgment) if the subject takes part in the 
trial. 
9. The Subject has clinically significant abnormal laboratory values at Screening visit 
(results to be checked at Baseline visit) that may either interfere with the interpretation of 
the trial results and/or put the subject at significant risk (according to the Investigator’s 
judgment) if the subject takes part in the trial.  
10. The Subject has known or suspected allergies or sensitivities to any components of any of 
the study drugs (see Investigator’s Brochure). 
11. The Subject is a Female who is lactating. 
12. The Subject is a Female who intends to conceive a child during the trial or for at least 1 
month after the last study drug application.  
13. The Subject is currently participating in any other clinical trial of a drug or medical 
device OR participated in any other clinical trial within the 30 days prior to the Baseline 
visit 
14. The Subject has received, applied, or ingested the following treatments within the 
specified time frame prior to the Baseline visit 
Topical treatment on the face and trunk:
Antibiotics,
Benzoyl peroxide, 
Azelaic acid, 
Zinc 
Corticosteroids 
Other topical treatments (including laser) 
2 weeks 
Retinoids
4 weeks
Topical procedures on the face and trunk:
Phototherapy devices for acne (e.g., ClearLight™) 
Adhesive cleansing strips (e.g., Pond®, Biore®)  
Cosmetic procedures (i.e., facials, peeling, comedone extraction) 
1 week 
Systemic treatment:


GALDERMA R&D 
Protocol Summary 
RD.06.SPR.18250 – 07 Aug 2014  
Page 7 of 13 
 
Non- steroidal anti-inflammatory drugs
2 weeks
Corticosteroids (except inhaled corticosteroids or intrathecal corticosteroids )
4 weeks
Antibiotics (except plain penicillin)
4 weeks
Oral retinoids
6 months
Immunomodulators, including biologics
6 months
Note: No time frame period is specified for Alpha-hydroxy acid products, medicated 
shaving creams, after-shaves, colognes, astringents, or preparations with alcohol, but 
their application is prohibited during the study.  
15. The Subject has been exposed to excessive ultraviolet (UV) radiation on the face and/or 
on the trunk treated area within one month prior to the Baseline visit or the subject is 
planning intense UV exposure during the study (i.e. occupational exposure to the sun, 
subject used to sunbathing, tanning salon use, phototherapy, etc.) 
16. The Subject is unwilling to refrain from use of prohibited medication during the clinical 
trial 
17. The Subject is vulnerable (e.g., deprived of freedom) as defined in Section 1.61 of 
International Conference on Harmonization (ICH) Guideline for Good Clinical Practice 
(GCP). 
 
Efficacy Assessments 
Efficacy will be evaluated as a secondary objective. IGA and PGA assessments are to be 
performed by a qualified investigator. Training is required for all evaluators who perform 
IGA/PGA. 
IGA (Investigator’s Global Assessment) of facial acne  
The areas defined for IGA assessment are forehead, each cheek, chin and nose. 
Investigators will evaluate the facial acne at predetermined visits (see table 1) according 
to the following scale. 
 
Investigator’s Global Assessment Scale (IGA)
0
Clear
Clear skin with no inflammatory or non inflammatory lesions.
1
Almost Clear
A few scattered comedones and a few small papules.
2
Mild
Easily recognizable; less than half the surface is involved. Some 
comedones and some papules and pustules. 
3
Moderate
More than half of the surface is involved. Many comedones, papules and 
pustules. One nodule may be present. 
4
Severe
Entire surface is involved. Covered with comedones, numerous papules 
and pustules.  Few nodules may be present. 
Note: At Screening and Baseline visits IGA assessment is to be done prior to lesion counts. Time of 
IGA assessment should be recorded in the source data and the eCRF (before assessing lesions 
counts on the face). 
 


GALDERMA R&D 
Protocol Summary 
RD.06.SPR.18250 – 07 Aug 2014  
Page 8 of 13 
 
PGA (Physician’s Global Assessment) of truncal acne  
The areas defined PGA assessment are shoulders, upper back and anterior chest which 
are accessible to self-application by the subject, i.e. the regions that the subject can 
easily reach and apply the study drug by himself or herself without assistance.  
Investigators will evaluate the truncal acne at predetermined visits (see table 1) 
according to the following scale. 
Specific requirements for children between 9 and 11 years old who do not have 
moderate acne on the trunk at Baseline (i.e. who do not have PGA of 3, at least 20 
inflammatory lesions on the trunk and at least 20 non-inflammatory lesions on the 
trunk): 
The PGA scale will be completed at all visits (including Week 1, 2, 4 and 8 visits), and 
used by the investigators to decide if they want to start the treatment for truncal acne.  
 
Physician Global Assessment Scale (PGA)
0
Clear
Clear skin with no inflammatory or non -inflammatory lesions.
1
Almost Clear
A few scattered comedones and a few small papules.
2
Mild
Easily recognizable; less than half the surface is involved. Some 
comedones and some papules and pustules. 
3
Moderate
 
More than half of the surface is involved. Many comedones, papules and 
pustules. One nodule may be present. 
4
Severe
 
Entire surface is involved. Covered with comedones, numerous papules and 
pustules. Few nodules may be present. 
Note: At Screening and Baseline visits PGA assessment is to be done prior to lesion counts. Time of 
PGA assessment should be recorded in the source data and the eCRF (before assessing lesions 
counts on the trunk). 
 
Efficacy Assessments  
• 
Success rate of IGA (defined as 0=clear or 1=almost clear) at each time point  
• 
Success rate of  PGA (defined as 0=clear or 1=almost clear) at each time point  
• 
Grade change from baseline of IGA at each time point  
• 
Grade change from baseline of PGA at each time point  
• 
Subject’s assessment of facial acne improvement at each time point. 
 
Safety Assessments 
• 
Local tolerability (erythema, scaling, dryness, and stinging/burning) on the face and 
trunk, 
• 
Adverse event,  
• 
Laboratory parameters,  


GALDERMA R&D 
Protocol Summary 
RD.06.SPR.18250 – 07 Aug 2014  
Page 9 of 13 
 
• 
Vital signs and physical examination 
 
Other Assessments 
• 
Lesion counts on the face and on the trunk at Screening and Baseline visit  
• 
DLQI and C-DLQI at each time point,  
• 
PK data 
In selected sites only, a PK assessment will be performed only in 9 to 11 year old subjects who 
have agreed in the parents/guardian ICF and Assent form to have a PK sample taken.  At week 4, 
the application will be done on site at this specific day at any time. One single blood sample will 
be collected 4 hours (± 10 min) after on-site study drug application.  
 
Principal Statistical Methods 
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. 
Any changes to the statistical analyses decided after the Database Lock should be justified and 
documented in the clinical trial report. 
 
Sample Size 
 
This study was designed to ensure that at least 300 subjects will be exposed to CD5789 50µg/g cream for 
6 months, and 100 subjects exposed for 1 year. 
 


GALDERMA R&D 
Protocol Summary 
RD.06.SPR.18250 – 07 Aug 2014  
Page 10 of 13 
 
Table 1 – Schedule of Assessments 
Scheduled Visits i 
Procedures 
Screening a 
(up to 14 days 
prior to 
Baseline) 
Baseline a 
Wk 1 
(±3 day) 
Wk 2 
(±3 day) 
Wk 4 
(± 3days) 
Wk 8 
(±3 days) 
Wk 12 
(±5days) 
Wk 20 
(±5days) 
Wk 26 
(±5 days) 
Wk 38 
(±5 days) 
Wk 52/ ET 
(±5 days) 
Unscheduledk k
Informed Consent/ HIPAA 
(US only)/ Assent Form/ 
Photo Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
X d 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
X d 
 
 
 
 
 
 
 
 
 
 
Previous 
Therapies/Procedures 
X 
 
 
 
 
 
 
 
 
 
 
 
Vital Signs/Physical 
Examination 
X 
X d 
 
 
 
 
X 
 
X 
 
X 
X 
Laboratory Safety Test 
X 
 
 
 
 
 
 
 
X 
 
X 
 
Urine Pregnancy Testing c 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Subject’s Assessment of 
Acne improvement (face) 
 
 
 
 
 
 
X 
 
X 
 
X 
 
Face and trunk 
Photographs (only in 
selected centers) 
 
X 
 
 
 
 
X 
 
X 
 
X 
 
IGA 
X 
X d 
 
 
 
 
X 
X 
X 
X 
X 
X 
PGA l 
X 
X d 
Xm 
Xm 
Xm 
Xm 
X 
X 
X 
X 
X 
X 
Acne Lesion Counting 
(face) 
X 
X d 
 
 
 
 
 
 
 
 
 
 
Acne Lesion Counting 
(trunk) e 
X 
X d 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
X d 
 
 
 
 
 
 
 
 
 
 
Local Tolerability (face) f 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Local Tolerability (trunk) f 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


GALDERMA R&D 
Protocol Summary 
RD.06.SPR.18250 – 07 Aug 2014  
Page 11 of 13 
 
Scheduled Visits i 
Procedures 
Screening a 
(up to 14 days 
prior to 
Baseline) 
Baseline a 
Wk 1 
(±3 day) 
Wk 2 
(±3 day) 
Wk 4 
(± 3days) 
Wk 8 
(±3 days) 
Wk 12 
(±5days) 
Wk 20 
(±5days) 
Wk 26 
(±5 days) 
Wk 38 
(±5 days) 
Wk 52/ ET 
(±5 days) 
Unscheduledk k
Adverse Event recording g 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pharmacokinetic 
assessment (only in 
selected sites and to 
eligible subjects [9 to 11 
years old]) 
 
 
 
 
X 
 
 
 
 
 
 
 
DLQI or C-DLQI 
 
X 
 
 
 
 
X 
 
X 
 
X 
 
Study drug dispensing (D) 
and Accountability (A) 
 
D 
 
 
D/A 
 
D/A j 
D/A j 
D/A j 
D/A j 
A j 
D 
Moisturizer/cleanser 
Dispensing (D) 
 
D 
 
 
D 
 
D 
D 
D 
D 
 
D 
Dosing calendar given (G) 
returned and reviewed (RR) 
 
G 
RR 
RR 
RR 
RR 
RR 
RR 
RR 
RR 
RR 
RR 
Concomitant 
therapies/procedures h 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Exit Form 
 
 
 
 
 
 
 
 
 
 
X b 
 
 
a) Baseline visit must be performed maximum 14 days after Screening. For women of childbearing potential, there must be 14 days between Screening and Baseline Visit (for UPT 
reason). No re-screen will be allowed  
b) Should be conducted earlier if subject discontinues prior to Week 52. 
c) For Subject of childbearing potential only: The determination of Urine Pregnancy Tests is mandatory at Screening, Baseline, Week 4, Week 8, Week 12, Week 20, Week 26 
,Week 38 and Week 52 before if there is early termination and in case of an Unscheduled Visit.  
d) Confirm information at Baseline. 
e) Lesion counts on the trunk : except for Children between 9 and 11 years old with no moderate acne on the trunk at Baseline 
f) 
The Baseline local tolerability assessment will occur prior the first study drug application on the given area. 
Subjects between 9 and 11 years old with no moderate acne on the trunk at Baseline (i.e. who do not have PGA of 3): the local tolerability assessment will only be performed if 
study drug treatment has been started on the trunk (based on investigator decision) 
g) Adverse events occurring from the time the informed consent is signed should be recorded in the eCRF.  
h) Medication that continues after Screening visit should be recorded on the Concomitant Medication page of the eCRF. Medical or surgical procedures occurring after Screening visit 
should be recorded on the Procedures page of the eCRF. 


GALDERMA R&D 
Protocol Summary 
RD.06.SPR.18250 – 07 Aug 2014  
Page 12 of 13 
 
i) 
To enhance subject compliance, a study window of plus or minus 3 days will be allowed for Week 1, Week 2; Week 4 and Week 8. A study window of plus or minus 5 days will be 
allowed for Weeks 12,  20, 26, 38, 52. All study visits should be scheduled based on the actual date of Baseline visit date. 
j) 
From Week 12 to Week 52 the dispensation will be done only if the skin assessment is not clear (IGA or PGA >=1); Accountability should occur only when a prescription has been 
done at the previous corresponding visit and the Subject returns the study drugs. 
k) An unscheduled visit can take place in case of need for any dose regimen adaptation or study drug restart necessary for managing local skin tolerability or acne flare. 
l) 
Mandatory PGA assessment for all the study population, at Screening, Baseline and all visits from Week 12. 
m) PGA assessment ONLY for Subjects  between 9 and 11 years old with no moderate acne on the trunk at Baseline. 
 


GALDERMA R&D 
Protocol Summary 
RD.06.SPR.18250 – 07 Aug 2014  
Page 13 of 13 
 
Table 2 – Description and usage of Study Drugs 
 
Investigational Product
Trade Name or Equivalent
N/A
Internal Code
CD5789 
Pharmaceutical Form
Cream
Strength/ Concentration
50µg/g 
Formula number
0219.0102
Packaging (type and size)
50mL bottle with pump and overcap
Storage conditions
Store below 25°C / 77°F, do not freeze, do not refrigerate
Dosage (total daily dose)
Apply a thin film on the face on affected and not affected areas. A pea-size amount for 
each area of the face (forehead, chin, nose and each cheek), should be used; avoiding 
the nostrils, mouth, lips, eyelids and periorbital areas.  
 
Apply a thin film on the trunk on the upper back, shoulders and anterior chest on the 
affected and not affected areas. At least a pea-size amount for each area of the trunk 
(right & left upper back, right & left shoulders and right & left anterior chest) should be 
used. 
Route
Topical
Dose Regimen
Once daily in the evening after washing the treated areas with preferred or the provided 
cleanser , the study drug will be applied.  
 
Subjects are also encouraged  to use their preferred moisturizer or provided moisturizer 
as desired but respecting an interval of approximately  1 hour (before and after) the 
study drug application. 
Duration of administration
Up to 52 Weeks (+/- 5 days)
Location of Treated Area
Face (forehead, chin, nose and each cheek) and trunk (upper back, shoulders and 
anterior chest)  
N/A = Not Applicable