Clinical trial NCT03250624
Conditions: Atopic Dermatitis
Sponsor: Galderma R&D
Start date: 2016-11-01; Completion date: 2017-06-26
Enrollment: 63 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Exploratory, multi-centric, randomized, vehicle-controlled, investigator-blind, parallel group study, involved participants with chronic lesions of Atopic Dermatitis (AD) to evaluate the local and systemic safety of CD5024 0.3% cream over a 6-week treatment period compared to its vehicle.

Detailed description:
Study application was performed once daily, 7 days a week for 6 weeks.

Arms: arm 1: None arm 2: None
Interventions: intervention 1: CD5024 0.3% cream intervention 2: Placebo
Intervention descriptions: intervention 1: Participants applied CD5024 0.3% cream topically in the evening to the affected areas as a thin film corresponding to approximately 2 milligrams per centimeter square (mg/cm\^2) once daily for 6 weeks. intervention 2: Participants applied placebo matched to CD5024 0.3% cream topically in the evening to the affected areas as a thin film corresponding to approximately 2 mg/cm\^2 once daily for 6 weeks.

Protocol documents:
Prot_000.pdf: 









































































































































































SAP_001.pdf: 
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St atisti c al A n al ysis Pl a n
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S A F E T Y A N D E F FI C A C Y O F C D 5 0 2 4 0. 3 % C R E A M I N S U B J E C T S WI T H 
A T O PI C D E R M A TI TI S
S T A TI S TI C A L A N A L Y SI S P L A N
R D. 0 3. S P R. 1 0 9 6 9 6
1 3 J U L Y 2 0 1 7
T his d oc u me nt is electr o nicall y  a p pr o ve d a n d si g ne d b y:  St atistic M a n a ger
N a me
Re as o n f or Si g ni n g
D ate
2 1-J ul- 2 0 1 7
C O N FI D E N TI A L  G A L D E R M A  
2 1- J ul- 2 0 1 7
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P P D
P P D


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A ut h or :
Res p o nsi ble of t he st atistic al a n al ysis
Re vie wer :
C O N FI D E N TI A L  G A L D E R M A  
2 1- J ul- 2 0 1 7
I nt er n all y A p pr o v e d
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P P D
P P D


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 3 of 53
DOCUMENT HISTORY
Version No. 
Description of Edits
Justification 
Date
Amendment 1
The analysis of the primary endpoint
changes from the percent change in EASI 
score from baseline to week 6 to the 
Change in EASI score from baseline to 
week 6 adjusted on baseline.  Change from 
baseline will be analyzed on ITT-LOCF, 
ITT-MI and PP.
As a secondary endpoint Percentage 
change in EASI score from baseline to any 
scheduled visits will be analyzed via a 
Cochran Mantel Haenszel test stratified by 
analysis center, using RIDIT transformation 
and Row mean score statistics. Percent 
change from baseline will be analyzed on 
ITT-LOCF and PP
During dry run, one observation (percent 
change from baseline of 200%) appears to 
deviate markedly from others. This patient 
has a very low EASI at baseline 
(EASI=1).This outlier skews the 
distribution and for the intended analysis 
(ANOVA) increases the residual error and 
thus makes the statistical test less 
powerful and not appropriate.
13/07/2017
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Pr ot o c ol N o: R D. 0 3. S P R. 1 0 9 6 9 6
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T A B L E O F C O N T E N T S
1
S T U D Y O B J E C TI V E S ...................................................................................................................... 6
2
S T U D Y D E SI G N ............................................................................................................................... 6
3
E F FI C A C Y A N D S A F E T Y V A RI A B L E S ..................................................................................... 8
3. 1
Effic ac y v ari a bles ......................................................................................................................... 8
3. 1. 1
Pri m ar y effic ac y
e n d p oi nts .................................................................................................... 8
3. 1. 2
Sec o n d ar y effic ac y e n d p oi nts ................................................................................................. 8
4
S A F E T Y A N D O T H E R V A RI A B L E S ............................................................................................ 8
.......................................................................................................................... 8
5
P O P U L A TI O N S A N A L Y Z E D ......................................................................................................... 9
5. 1
I nte nt-t o-tre at (I T T) Effic ac y a n al ysis set.................................................................................. 9
5. 2
Per -pr ot oc ol ( P P) Effic ac y a n al ysis set....................................................................................... 9
5. 3
S afet y p o p ul ati o n .......................................................................................................................... 9
5. 4
P K set ............................................................................................................................................. 9
6
S A M P L E SI Z E C O N S I D E R A TI O N............................................................................................ 1 0
7
S T A TI S TI C A L M E T H O D S
A N D D A T A C O N SI D E R A TI O N S ............................................ 1 0
7. 1
St u d y s u bjects ............................................................................................................................. 1 0
7. 1. 1
Dis p ositi o n of
s u bjects........................................................................................................... 1 0
7. 1. 2
Pr ot oc ol de vi ati o ns ................................................................................................................ 1 0
7. 2
Effic ac y a n al ysis ......................................................................................................................... 1 1
7. 2. 1
D at a sets a n al yze d ................................................................................................................. 1 1
7. 2. 2
De m o gr a p hic a n d b aseli ne c h ar acteristics .......................................................................... 1 1
7. 2. 3
Me dic al hist or y, pre vi o us a n d c o nc o mit a nt t her a pies a n d pre vi o us a n d 
c o nc o mit a nt pr oce d ures ........................................................................................................ 1 1
7. 2. 4
C o m pli a nce ............................................................................................................................. 1 1
7. 2. 5
St atistic al a n al ysis f or effic ac y ............................................................................................. 1 2
7. 2. 6
St atistic al a n d a n al ytic al iss u es ........................................................................................... 1 3
7. 3
S afet y a n al ysis ............................................................................................................................. 1 4
7. 3. 1
E xte nt of
e x p os ure ................................................................................................................. 1 4
C O N FI D E N TI A L  G A L D E R M A  
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..................................................................................................................... 1 5
7. 3. 3
L a b or at or y p ar a meters ........................................................................................................ 1 5
7. 3. 4
Vit al si g ns, p h ysic al fi n di n gs a n d ot her o bser v ati o ns rel ate d t o s afet y ............................ 1 5
................................................................................................................. 1 6
................................................................................................................. 1 6
................................................................................................................. 1 6
7. 5
A n al ys is visit defi niti o n .............................................................................................................. 1 6
8
C H A N G E S F R O M T H E P R O T O C O L A N A L Y SI S P L A N ..................................................... 1 7
9
T A B L E S, FI G U R E S, A N D G R A P H S ........................................................................................... 1 7
9. 1
St u d y s u bject ............................................................................................................................... 1 7
9. 2
Effic ac y a n al ysis ......................................................................................................................... 2 3
9. 2. 1
Pri m ar y effic ac y e n d p oi nt ..................................................................................................... 2 3
9. 2. 2
Sec o n d ar y effic ac y e n d p oi nts ............................................................................................... 3 2
9. 2. 3
S u b gr o u p a n al yses ................................................................................................................ 4 4
9. 3
S afet y a n al ysis ............................................................................................................................. 4 6
9. 3. 1
E x te nt of e x p os ure ................................................................................................................. 4 6
....................................................................................................... 4 7
9. 3. 3
L a b or at or y p ar a meters ........................................................................................................ 5 0
9. 3. 4
Vit al Si g n a n d p h ysic al e x a mi n ati o n a n d ot her i nf or m ati o n rel ate d t o s afet y ................. 5 5
.................................................................................................... 5 7
C O N FI D E N TI A L  G A L D E R M A  
2 1- J ul- 2 0 1 7
I nt er n all y A p pr o v e d
C CI
C CI
C CI
C CI


Pr ot o c ol N o: R D. 0 3. S P R. 1 0 9 6 9 6
St atisti c al A n al ysis Pl a n
P a g e 6 of 5 3
1
S T U D Y O B J E C TI V E S
T he pri mar y  objecti ve of t his st u d y is t o e val uate t he l ocal a n d s yste mic safet y of C D 5 0 2 4 0. 3 % 
crea m a p plie d o nce d ail y  over a 6- wee k treat me nt peri o d i n a d ults wit h c hr o nic lesi o ns of
m o derate at o pic der matitis ( A D), c o m pare d t o its ve hicle.
T he sec o n dary o bjecti ve is t o e val uate t he efficac y of C D 5 0 2 4 0. 3 % crea m vers us its ve hicle o n 
c hr o nic lesi o ns of m o derate A D.
2
S T U D Y D E SI G N
T his 
is a n e x pl orat or y, m ulti -ce nter (a p pr o xi matel y 5 sites i n Ca na da), 
ra n d o mize d, 
ve hicle -c o ntr olle d, i n vesti gat or-bli n d, parallel gr o u p st u d y, i n v ol vi n g a p pr oxi matel y  85 s u bjects
scree ne d t o get a p pr o xi matel y 60 ra n d o mize d s u bjects wit h c hr o nic lesi o ns of A D meeti n g 
s pecific i ncl usi o n/ n o n-i ncl usi o n criteria. T he i n vesti gat or a n d/ or ot her e val uat or(s) will n ot c o me 
i nt o c o ntact wit h t he st u d y materials. S u bjects a n d t he st u d y staff d o n ot ha ve access t o t he 
c orres p o n de nce bet wee n t he kit n u m ber a n d t he assi g ne d treat me nt  gr o u p.
S u bjects w h o c o nse nt t o be e nr olle d a n d f ulfill st u d y criteria will be all ocate d t o o ne of t he st u d y 
treat me nt acc or di n g t o t he ra n d o mizati o n list, i n a 1:1 rati o (f or e xa m ple Gr o u p A: N = 3 0 s u bjects 
treate d wit h C D 5 0 2 4 0. 3 % crea m, a n d Gr o u p B: N = 3 0 s u bjects treate d wit h t he   ve hicle).
C O N FI D E N TI A L  G A L D E R M A  
2 1- J ul- 2 0 1 7
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C CI


Pr ot o c ol N o: R D. 0 3. S P R. 1 0 9 6 9 6
St atisti c al A n al ysis Pl a n
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Effic ac y a n d s afet y assess me nts
S cr e e ni n g 
p eri o d
Tr e at m e nt P eri o d
E arl y  
T er mi n a 
ti o n
U n s c h e
d ul e d
F oll o w
-u p
W e e k -5 t o 
W e e k - 1
W e e k 1
W e e k 2
W e e k 3
W e e k 4
W e e k 5
W e e k 6
W e e k 
7
W e e k 
9
D -3 0 t o D -3
D 0 1
D 0 2 t o 
D 0 7
D 0 8
D 0 9 t o 
D 1 4
D 1 5
D 1 6 t o 
D 2 1
D 2 2
D 2 3 t o 
D 2 8
D 2 9
D 3 0 t o 
D 3 5
D 3 6
D 3 7 t o 
D 4 2
D 4 3
D 5 4 ± 2
Effi c a c y a s s e s s m e nt
E A SI S c or e
X
X
X
X
X
X
X ( b)
X 
X
I n v e sti g at or Gl o b al A s s e s s m e nt (I G A)
X 
X
X
X
X
X
X
X ( b)
X
T S S
X
X
X
X
X
X
X ( b)
X
M o difi e d -O bj e cti v e S C O R A D
X
X
X
X
X
X
X ( b)
X
H a n d I G A w h e n a p pli c a bl e
X
X
X
X
X
X
X ( b)
X
t B S A ( T ot al B o d y S urf a c e Ar e a)
X
B S A (i. e. aff e ct e d b y A D)
X 
X
X
X
X
X
X
X ( b)
X 
X
P ati e nt- r e p ort e d O ut c o m e - Pr urit u s N u m eri c al 
R ati n g S c al e & DI A R Y
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
X ( b)
X
P ati e nt- r e p ort e d O ut c o m e - Pr urit u s V er b al 
R ati n g S c al e & DI A R Y
X
X ( b)
X
S af et y a s s e s s m e nt
Bl o o d s a m pli n g s ( c o a g ul ati o n, h e m at ol o g y, 
bi o c h e mi str y)
X
X
X 
X
Bl o o d s a m pli n g s (I g E & T A R C)
X
X 
X
P h y si c al e x a mi n ati o n
X 
X
X
X
X 
X
X
Vit al si g n s
X 
X
X
X
X 
X
X
E C G
X 
X
X 
X
Ot h er a s s e s s m e nt
( b) All a s s e s s m e nt s ar e t o b e d o n e b ef or e a n y pr o c e d ur e s ar e p erf or m e d.
 
C O N FI D E N TI A L  G A L D E R M A  
2 1- J ul- 2 0 1 7
I nt er n all y A p pr o v e d
C CI
C CI
C CI


Pr ot o c ol N o: R D. 0 3. S P R. 1 0 9 6 9 6
St atisti c al A n al ysis Pl a n
Pa ge 8 of 5 7
3
E F FI C A C Y A N D S A F E T Y
V A RI A B L E S
3. 1
Effic ac y v ari a bles
3. 1. 1
Pri m ar y effic ac y e n d p oi nts
T he Pri mar y  efficac y e n d p oi nt is t he c ha n ge fr o m Baseli ne t o Wee k 6 of t he E A SI sc ore.
3. 1. 2 
Sec o n d ar y effic ac y e n d p oi nts
T he c ha n ge fr o m Baseli ne of t he E A SI sc ore at a n y ot her e val uati o n visit a n d t he perce nt c ha n ge 
fr o m Baseli ne i n E A SI sc ore at eac h e val uati o n visit.
I n vesti gat or Gl o bal Assess me nt i n ter ms of distri b uti o n a n d i n ter ms of s uccess rate (s uccess is 
defi ne d as a s u bject wit h a n I G A sc ore of 0 [clear] or 1 [ Al m ost clear]) at eac h e val u ati o n visit.
Perce nt c ha n ge fr o m Baseli ne of t he T otal S u m Sc ore ( T S S) of t he tar get pla q ue.
C ha n ge 
fr o m 
Baseli ne 
of 
eac h 
i n di vi d ual 
sc ore 
( Er yt he ma,
I nd urati o n/ Pa p ulati o n, 
O ozi n g/ Cr usti n g, E xc oriati o n, Li c he nificati o n).
Perce nt C ha n ge fr o m basel i ne of t he M o difie d O bjecti ve S C O R A D.
Pr urit us ( n u merical rati n g scale [ N R S], ver bal rati n g scale [ V R S]) a n d t heir c ha n ges fr o m
Baseli ne at eac h e val uati o n visit.
4
S A F E T Y A N D O T H E R V A RI A B L E S
P h y sical e xa mi nati o n, Vital si g ns ( p ulse rate a n d bl o o d press ure)
La b orat or y para meters
A d verse e ve nts
C O N FI D E N TI A L  G A L D E R M A  
2 1- J ul- 2 0 1 7
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Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 9 of 57
5
POPULATIONS ANALYZED
5.1
Intent-to-treat (ITT) Efficacy analysis set
The ITT set is defined as any subjects who are randomized. Data from subjects included in the 
ITT population will be analyzed according to the treatment as randomized.
5.2
Per-protocol (PP) Efficacy analysis set
The PP set is defined as the ITT population, after exclusion of subjects deemed 
non-evaluable for efficacy due to major deviations from the protocol. Major deviations are 
divided into 4 categories:
Entrance criteria deviations,
Non-compliance,
Concomitant therapies taken during the study and/or Concomitant illnesses, 
interfering with efficacy,
Administrative errors such as unblinding or study drug dispensing errors.
Major deviations will be identified and categorized before database lock and unblinding, 
during a blind data review meeting.
5.3
Safety population
The Safety set is defined as comprising the ITT Population subjects who applied/were 
administered the study drug(s) at least once. In practice, only the subjects who return their
study drug(s) unopened will be excluded from the Safety Population. All safety data will be
summarized based on the Safety Population.
5.4
PK set
The PK set is defined as comprising all subjects from the safety set who have signed the ICF
for PK samples and who provide at least one post-baseline evaluable drug concentration
value. All PK data will be based on observed cases.
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 10 of 57
6
SAMPLESIZECONSIDERATION
In a previous Galderma R&D trial (SPR.18158) where a Vehicle was used in atopic 
dermatitis in subjects with involved BSA between 5% and 20%, the Vehicle percent change 
from Baseline at Week 4 of a modified EASI (No Head and Neck) was -40% and the 
standard deviation (SD) was 45%.
In studies evaluating Dupilumab versus placebo, the observed placebo EASI score percent 
changes from Baseline at Week 4 ranged from -17% to -25% with a SD around 40% 
(Beck 2014), and was - 18% at Week 16 with a standard deviation of 40% (Thaci 2016). In
this last trial it was observed that these values were reached from week 4 onwards. Based on 
these historical data, the SD was set at 40%.
The magnitude of effect of Dupilumab reached 45% over placebo. However, systemic 
immunosuppressant drug for atopic dermatitis are generally more effective than topical 
treatments (Thaci 2016). Taking that into account, for CD5024 cream 0.3% applied once
daily, an effect of 30% over its vehicle would be considered as clinically relevant.
Consequently, the effect size (delta/sigma) has been set at 0.75 (30%/40%).
Using a randomization ratio of 1:1 for CD5024 cream 0.3% QD and vehicle, a sample size of 
30 randomized subjects in each treatment group can ensure an 80% power to detect a
difference of 30 % between CD5024 and its vehicle on EASI score mean percent change from
Baseline.
7
STATISTICALMETHODS AND DATA CONSIDERATIONS
For statistical analyses purpose, baseline is defined as the last measurement prior to the first 
application of the study drug. This is true for all variables except NRS, for which baseline is
the mean of the values collected from Day -3 to Day -1.
7.1
Study subjects
7.1.1
Disposition of subjects
Reasons for early discontinuation, and normal completions, will be summarized using frequency 
distribution (n, %).
7.1.2
Protocol deviations
Major protocol deviations will be summarized overall using frequency distribution (n, %).
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 11 of 57
7.2
Efficacy analysis
7.2.1
Data sets analyzed
Number of subjects included in each efficacy analyses (ITT, PP) and number of subjects included 
in the safety analysis will be presented by treatment.
7.2.2
Demographic and baseline characteristics
The subject demographics and baseline characteristics will be summarized by descriptive 
statistics.
Frequency distribution (n, %), for qualitative  criteria,
Usual statistics (n, mean, standard deviation, median, min, max), for quantitative criteria,
Both frequency distribution and usual statistics for ordinal criteria.
7.2.3
Medical history, previous and concomitant therapies and previous and 
concomitant procedures
Frequency distribution of subjects with at least one previous or/and concomitant disease at  
inclusion will be given.
Previous and Concomitant therapies will be descriptively summarized on the safety population. 
Previous and concomitant procedures will be summarized in the same way using MedDRA 
dictionary v19.0.
Therapies and procedures ongoing at the baseline visit or starting after the baseline visit will be 
summarized in concomitant therapies /procedures and those ending at baseline or before will be 
summarized in previous therapies / procedures.
7.2.4
Compliance
Non-Compliance is defined as subjects who have a deviation of more than 20% from the planned 
42 applications (i.e. less than 34 applications or more than 50 applications).
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 12 of 57
7.2.5
Statistical analysis for efficacy
A type I error of 0.05 (two-sided test) will be used to declare statistical  significance.
All efficacy variables will be summarized by treatment at each visit. The categorical variables 
(e.g. IGA), and their changes from Baseline will be summarized by frequency and percentage for 
each response category (N, %). The continuous variables (EASI, objective SCORAD, TSS, and 
their change or percent changes, Pruritus [weekly average NRS and the VRS] and their changes  
from Baseline) will be summarized using means, medians, Q1, Q3, minimum, maximum, and 
standard deviations.
The Primary efficacy endpoint, the change from Baseline to Week 6 of the EASI score, will be 
analyzed using an analysis of covariance (ANCOVA) with the Treatment group as factor and 
Analysis center as a cofactor and EASI score at baseline as a covariate. The p-value for the 
treatment comparison, estimate of the Least Square means (LSmeans) treatment difference 
(CD5024 – Vehicle), will be generated from the ANCOVA model.
The change from Baseline in EASI score at any other evaluation visit, will be analyzed using 
analysis of covariance with the Treatment group as factor, Analysis center as a cofactor and EASI 
score at baseline as a covariate. The p- value for the treatment comparison, estimate of the 
LSmeans treatment difference (CD5024 – Vehicle), will be generated from the ANCOVA model.
Percent change from Baseline in EASI score at each evaluation visit will be analyzed by a CMH 
test stratified by analysis center with the ridit transformation and the row mean score difference 
statistic (FREQ procedure from SAS).
Modified objective SCORAD and TSS least square mean percent change from Baseline at each 
evaluation visit, will be analyzed individually using analysis of  variance  with  the  Treatment 
group as factor and analysis center as a cofactor.
Distribution of individual scores and their changes from Baseline, will be analyzed at each 
evaluation visit using the Cochran-Mantel-Haenszel (CMH) test stratified by analysis center with 
the ridit transformation and the row mean score difference statistic (FREQ procedure from
SAS).
Proportion of subjects achieving success (IGA=0 [clear] or IGA=1 [Almost clear]) will be 
analyzed at each evaluation visit using the CMH test stratified by analysis center with the ridit 
transformation and the general association statistic (FREQ procedure from  SAS).
Change in Pruritus (Weekly average NRS based on at least 4 daily scores and the VRS) will be 
separately analyzed at each evaluation visit by the CMH test stratified by analysis center with the 
ridit transformation and the row mean difference statistic (FREQ procedure from   SAS).
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 13 of 57
7.2.6
Statistical and analytical issues
7.2.6.1
Adjustment for covariates
NA.
7.2.6.2
Handling of dropouts or missing data
For the primary endpoint (change from Baseline in EASI score) several sensitivity analyses will 
be conducted in ITT population:
The primary imputation method will use the LOCF (Last observation carried forward) 
approach.
For sensitivity purpose, the method of imputation for missing data will be MI (Multiple 
Imputation) using the Missing At Random (MAR) assumption. The MI procedure of the SAS 
system will be used to generate five sets of data with missing values imputed from observed 
data. It is expected that the pattern of missing data will be monotonic, with slight deviations 
being corrected by the Markov Chain Monte Carlo (MCMC) method of the MI procedure. 
Linear regression will be employed to model the missing EASI score, with the following 
covariates included in the imputation model:  treatment and non-missing data from earlier 
timepoints. The imputed datasets will be analyzed using the methodology described for change 
from Baseline in EASI score. The results from the analysis of the multiple imputed datasets 
will be combined by the MIANALYZE procedure of the SAS system. The seed number to be 
used will be the protocol number (109696).
For secondary endpoints the LOCF method will be used.
7.2.6.3
Interim analyses and data monitoring
NA
7.2.6.4
Multicenter studies
Analysis center will be defined during the blind review meeting and will be included as a cofactor 
in the inferential analyses of primary and secondary endpoints.
7.2.6.5
Multiple comparison/multiplicity
The primary purpose is to compare CD5024 cream 0.3% QD daily to its vehicle in terms of EASI 
score. P-values for secondary criteria will be given for indicative purposes, so no adjustment will
be made. All tests will be two-sided and significance will be declared at a 5% two-sided level.
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 14 of 57
7.2.6.6
Use of a subset of patients
The protocol deviations will be identified during the blind review, and some of them will lead to 
the exclusion of the subjects from the PP analyses. PP analyses will be performed on primary and 
secondary endpoints.
7.2.6.7
Active-Control studies intended to show equivalence
NA.
7.2.6.8
Examination of Subgroups
Subgroup analyses will be explored by IgE on the primary endpoint. A threshold will be defined 
during the blind review.
7.3
Safety analysis
7.3.1
Extent of exposure
7.3.1.1
Treatment duration
Treatment duration will be calculated as the difference in days between the date of last 
application of medication and the date of first use + 1 during Period A. Date of last visit under 
treatment will be used if the date of last use is not  available.
7.3.1.2
Quantity of product used
All collected and weighed packaging of product will be used to determine the quantity of product 
used per subject. Total Medication usage (g) and Daily medication usage (g/day) will be 
summarized by descriptive statistics. The variables will be derived by the   following:

Total medication used = total dispensed weight (g) - total returned weight (g)

Daily medication used = total medication used (g) / treatment duration (day)
As the subject will be instructed by a member of the staff on how to measure the prescribed dose 
using fingertip units (FTU), FTU will be summarized the same way as the medication used, Total 
and Daily FTU.
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Pr ot o c ol N o: R D. 0 3. S P R. 1 0 9 6 9 6
St atisti c al A n al ysis Pl a n
Pa ge 1 5 of 5 7
7. 3. 3
L a b or at or y p ar a meters
F or eac h para meter, s hift ta bles prese nti n g: pre -treat me nt (t he val ue o btai ne d cl osest a n d pri or t o 
t he first a p plicati o n, i n case of retest) vers us Da y  22 a n d D a y  43/ Earl y ter mi nati o n (last 
p ost -baseli ne val ue o n treat me nt) will be ge nerate d. T he n u m ber a n d perce nta ge of s u bjects 
bel o w, wit hi n, a n d a b o ve t he la b orat or y refere nce ra n ges will be s u m marize d. T he perce nta ge 
will be base d o n
t he n u m ber of s u bjects wit h
data a vaila ble f or b ot h pre -treat me nt a n d
p ost -treat me nt.
Descri pti ve statistics ( n, mea n, mi n, ma x a n d me dia n) will be perf or me d f or pre -treat me nt val ue, 
D a y  22 a n d D a y  43/ Earl y  ter mi nati o n. C ha n ge fr o m baseli ne t o Da y  22 a n d t o Da y  43/ Earl y 
ter mi nati o n val ue will als o be s u m marize d.
T he ma xi mal val ue will be i m p ute d f or a n y la b orat or y val ues bel o w t he li mit of q ua ntificati o n 
(e. g. “ X” will be use d f or “ < X”).
I n case a para meter w o ul d a val ue ‘ > X’ n o i m p utati o n will be ma de a n d n o mea n a n d sta n dar d 
de viati o n will be o ut p ut as f or I g E a n d Creati ni ne Cleara nce. F or Creati ni ne Cleara nce t he 
a nal ys is will be s u m marize d i n  cate g ories :
Cr e ati ni n e Cl e ar a n c e
> 9 0 m L/ mi n/ 1. 7 3 m²
6 0 -8 9 m L/ mi n/ 1. 7 3 m²
3 0 -5 9 m L/ mi n/ 1. 7 3 m²
1 5 - 2 9 m L/ mi n/ 1. 7 3 m²
< 1 5 m L/ mi n/ 1. 7 3 m²
7. 3. 4
Vit al si g ns, p h ysic al fi n di n gs a n d ot her o bser v ati o ns rel ate d t o s afet y
Vital si g ns, p h ys ical e xa mi nati o n a n d E C G will be descri pti vel y s u m marize d.
C O N FI D E N TI A L  G A L D E R M A  
2 1- J ul- 2 0 1 7
I nt er n all y A p pr o v e d
C CI


Pr ot o c ol N o: R D. 0 3. S P R. 1 0 9 6 9 6
St atisti c al A n al ysis Pl a n
Pa ge 1 6 of 5 7
7. 5
A n al ysis visit defi niti o n
If m ulti ple meas ure me nts are ta ke n i n t he sa me i nter val, t he o ne cl osest t o t he tar get st u d y da y 
will be use d f or t he a nal ysis. If t w o meas u re me nts are ta ke n wit h e q ual differe nces i n ti mi n g 
c o m pare d wit h t he tar get date, t he n o mi nal visit n u m ber (rec or de d o n t he C R F pa ge) will be use d. 
A nal y sis visit will a p pl y t o t he s u m maries a n d a nal yses of all efficac y varia bles.
A n al y s i s Vi sit
A n al y s i s Vi sit 
n u m b er
T ar g et 
St u d y  D a y
Vi sit Wi n d o w ( St u d y  D ay)
B a s eli n e
B a s eli n e
1
[≤ 1 ]
W e e k 1
W e e k 1
8
[ 2 – 1 1]
W e e k 2
W e e k 2
1 5
[ 1 2 – 1 8]
W e e k 3
W e e k 3
2 2
[ 1 9 – 2 5]
W e e k 4
W e e k 4
2 9
[ 2 6 – 3 2]
W e e k 5
W e e k 5
3 6
[ 3 3 – 3 9]
W e e k 6
W e e k 6
4 3
[ 4 0 - 4 6]
C O N FI D E N TI A L  G A L D E R M A  
2 1- J ul- 2 0 1 7
I nt er n all y A p pr o v e d
C CI


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 17 of 57
8
CHANGES FROM THE PROTOCOL ANALYSIS PLAN
The initial analysis plan was to perform an ANOVA on the percent change from baseline to week 
6 in EASI score, but one observation appears to deviate markedly from others (200% increase of 
the EASI score). This outlier skews the distribution and for the intended analysis (ANOVA) 
increases the residual error and thus makes the statistical test less powerful and less appropriate. 
Then, the change from Baseline in EASI score at Week 6 will be the primary endpoint and will 
be analyzed via an ANCOVA with treatment as factor, analysis center as a cofactor and EASI at 
Baseline as covariate. This analysis will be conducted on ITT-LOCF, ITT-MI and PP population. 
Percent change from baseline at any scheduled visits will be secondary and will be analyzed via a 
CMH test using RIDIT transformation and row mean score statistics. This analysis will be 
conducted on ITT-LOCF and PP population.
9
TABLES, FIGURES, AND GRAPHS
9.1
Study subject
Table 9.1.1
Enrolment by country and investigator
CD5024
Vehicle
Overall
xx
xx
5xxx-PR. XXX
xx
xx
5yyy-PR. YYY
xx
xx
….
Table 9.1.2
Reason for discontinuation
CD5024
Vehicle
N (%)
xx
xx
Normal Completion
xx (x.xx%)
xx (x.xx%)
Adverse Event
xx (x.xx%)
xx (x.xx%)
Subject's Request
xx (x.xx%)
xx (x.xx%)
Lost to Follow-up
xx (x.xx%)
xx (x.xx%)
Other
xx (x.xx%)
xx (x.xx%)
…
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 18 of 57
Table 9.1.3
Demographic data
CD5024
Vehicle
N
xx
xx
Gender
Female
xx(xx.x%)
xx(xx.x%)
Male
xx(xx.x%)
xx(xx.x%)
Race
White
xx(xx.x%)
xx(xx.x%)
…
xx(xx.x%)
xx(xx.x%)
Age (in Years)
Mean±SD
xx.x (xx.x)
xx.x (xx.x)
Median
xx
xx
Min;Max
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
Table 9.1.4
Baseline disease characteristics
CD5024
Vehicle
IGA
N
xx
xx
0-Clear
xx (xx.x%)
xx(xx.x%)
1-Almost Clear
xx (xx.x%)
xx(xx.x%)
2-Mild
xx (xx.x%)
xx(xx.x%)
3-Moderate
xx (xx.x%)
xx(xx.x%)
4-Severe
xx (xx.x%)
xx(xx.x%)
Hand IGA
N
xx
xx
0-Clear
xx (xx.x%)
xx(xx.x%)
1-Almost Clear
xx (xx.x%)
xx(xx.x%)
2-Mild
xx (xx.x%)
xx(xx.x%)
3-Moderate
xx (xx.x%)
xx(xx.x%)
4-Severe
xx (xx.x%)
xx(xx.x%)
tBSA
N
xx
xx
Mean±SD
xx.x (xx.x)
xx.x (xx.x)
Median
xx
xx
Min;Max
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
BSA affected
N
xx
xx
Mean±SD
xx.x (xx.x)
xx.x (xx.x)
Median
xx
xx
Min;Max
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
EASI
N
xx
xx
Mean±SD
xx.x (xx.x)
xx.x (xx.x)
Median
xx
xx
Min;Max
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 19 of 57
CD5024
Vehicle
Modified SCORAD
N
xx
xx
Mean±SD
xx.x (xx.x)
xx.x (xx.x)
Median
xx
xx
Min;Max
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
VRS
N
xx
xx
Mean±SD
xx.x (xx.x)
xx.x (xx.x)
Median
xx
xx
Min;Max
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
NRS
N
xx
xx
Mean±SD
xx.x (xx.x)
xx.x (xx.x)
Median
xx
xx
Min;Max
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
TSS
N
xx
xx
Mean±SD
xx.x (xx.x)
xx.x (xx.x)
Median
xx
xx
Min;Max
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
Erythema
N
xx
xx
0-Clear
xx (xx.x%)
xx (xx.x%)
1-Almost Clear
xx (xx.x%)
xx (xx.x%)
2-Mild
xx (xx.x%)
xx (xx.x%)
3-Moderate
xx (xx.x%)
xx (xx.x%)
4-Severe
xx (xx.x%)
xx (xx.x%)
Induration / Papulation
N
xx
xx
0-Clear
xx (xx.x%)
xx (xx.x%)
1-Almost Clear
xx (xx.x%)
xx (xx.x%)
2-Mild
xx (xx.x%)
xx (xx.x%)
3-Moderate
xx (xx.x%)
xx (xx.x%)
4-Severe
xx (xx.x%)
xx (xx.x%)
Oozing / Crusting
N
xx
xx
0-Clear
xx (xx.x%)
xx (xx.x%)
1-Almost Clear
xx (xx.x%)
xx (xx.x%)
2-Mild
xx (xx.x%)
xx (xx.x%)
3-Moderate
xx (xx.x%)
xx (xx.x%)
4-Severe
xx (xx.x%)
xx (xx.x%)
Excoriation
N
xx
xx
0-Clear
xx (xx.x%)
xx (xx.x%)
1-Almost Clear
xx (xx.x%)
xx (xx.x%)
2-Mild
xx (xx.x%)
xx (xx.x%)
3-Moderate
xx (xx.x%)
xx (xx.x%)
4-Severe
xx (xx.x%)
xx (xx.x%)
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 20 of 57
CD5024
Vehicle
Lichenification
N
xx
xx
0-Clear
xx (xx.x%)
xx (xx.x%)
1-Almost Clear
xx (xx.x%)
xx (xx.x%)
2-Mild
xx (xx.x%)
xx (xx.x%)
3-Moderate
xx (xx.x%)
xx (xx.x%)
4-Severe
xx (xx.x%)
xx (xx.x%)
Table 9.1.5
Dataset analyzed
CD5024
Vehicle
Total
Screened subjects
-
-
xx
ITT population
xx (x.xx%)
xx (x.xx%)
xx (x.xx%)
PP population
xx (x.xx%)
xx (x.xx%)
xx (x.xx%)
Safety population
xx (x.xx%)
xx (x.xx%)
xx (x.xx%)
PK set
xx (x.xx%)
xx (x.xx%)
xx (x.xx%)
Table 9.1.6
Medical history
CD5024
Vehicle
Medical History
N (%)
xx
xx
Yes
xx (xx.x%)
xx (xx.x%)
No
xx (xx.x%)
xx (xx.x%)
Table 9.1.7
Previous therapies
CD5024
Vehicle
n 
therapies
n subjects % subj.
n 
therapies
n 
subjects
% subj.
Subjects with at least one previous therapy*
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
ATC Text#1
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #1
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #2
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #3
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
ATC Text#2
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #1
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #2
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #3
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
ATC Text#3
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #1
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #2
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #3
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
ATC Text#x…..
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
…..
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
*Multiple reports by each subject are possible
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 21 of 57
Table 9.1.8
Concomitant therapies
CD5024
Vehicle
n 
therapies
n subjects % subj.
n 
therapies
n 
subjects
% subj.
Subjects with at least one concomitant therapy*
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
ATC Text#1
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #1
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #2
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #3
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
ATC Text#2
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #1
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #2
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #3
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
ATC Text#3
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #1
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #2
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #3
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
ATC Text#x…..
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
…..
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
*Multiple reports by each subject are possible
Table 9.1.9
Summary of Previous Procedures and Non-Drug Therapies
CD5024
Vehicle
n 
procedure
s
n 
subjects
%
subj.
n 
procedure
s
n 
subjects
%
subj.
Subjects with at least one previous procedures and non 
drug therapy*
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
SOC#1
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #1
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #2
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #3
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
SOC#2
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #1
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #2
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #3
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
SOC#3
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #1
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #2
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #3
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
SOC #x…..
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
…..
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
*Multiple reports by each subject are possible
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 22 of 57
Table 9.1.10 Summary of concomitant Procedures and Non-Drug Therapies
CD5024
Vehicle
n 
procedure
s
n 
subjects
%
subj.
n 
procedure
s
n 
subjects
%
subj.
Subjects with at least one concomitant procedures and 
non drug therapy*
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
SOC#1
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #1
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #2
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #3
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
SOC#2
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #1
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #2
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #3
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
SOC#3
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #1
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #2
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Preferred term #3
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
SOC #x…..
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
…..
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
*Multiple reports by each subject are possible
Table 9.1.11 Subject with major protocol deviations
CD5024
Vehicle
N
subj.*
%
subj
N
subj.*
%
subj
AT LEAST ONE MAJOR DEVIATION*
xx
xx.x
xx
xx.x
entrance criteria deviations (at baseline)
x
x.x
x
x.x
concomitant therapies taken during the study
x
x.x
x
x.x
….
x
x.x
x
x.x
* Subjects with at least one major deviation
Numbers in columns cannot be added because a given subject may have reported more than one deviation
Table 9.1.12 Compliance
CD5024
Vehicle
N
subj.*
%
subj
N
subj.*
%
subj
<34 applications
x
x.x
x
x.x
34 to 50 applications
x
x.x
x
x.x
>50 applications
x
x.x
x
x.x
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 23 of 57
9.2
Efficacy analysis
9.2.1
Primary efficacy endpoint
Table 9.2.1.1 Descriptive results of the change from baseline in EASI score at each 
timepoint – ITT-LOCF
CD5024
Vehicle
Raw Data
Change from 
baseline
Raw Data
Change from 
baseline
Baseline
N
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
Median
xx
xx
Min;Max
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
Day 8-LOCF
N
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 15-LOCF
N
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 22-LOCF
N
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 29-LOCF
N
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 24 of 57
CD5024
Vehicle
Raw Data
Change from 
baseline
Raw Data
Change from 
baseline
Day 36-LOCF
N
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 43-LOCF
N
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Table 9.2.1.2 Statistical analysis of the change from baseline in score EASI at each 
timepoint – ITT-LOCF
CD5024
Vehicle
CD5024- Vehicle
Baseline
N
xx
xx
-
Mean
xx
xx
xx
SD
xx
xx
xx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
Day 8-LOCF
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
Day 15-LOCF
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
Day 22-LOCF
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
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Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 25 of 57
CD5024
Vehicle
CD5024- Vehicle
Day 29-LOCF
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
Day 36-LOCF
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
Day 43-LOCF
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
(1) p-values from the ANCOVA model include treatment, analysis center and baseline EASI scores
Table 9.2.1.3 Statistical analysis of the change from baseline in score EASI at each 
timepoint – ITT-MI
CD5024
Vehicle
CD5024- Vehicle
Baseline
N
xx
xx
-
Mean
xx
xx
xx
SD
xx
xx
xx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
Day 8-MI
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
Day 15-MI
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
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Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 26 of 57
CD5024
Vehicle
CD5024- Vehicle
Day 22-MI
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
Day 29-MI
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
Day 36-MI
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
Day 43-MI
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
(1) p-values from the ANCOVA model include treatment, analysis center and baselineEASI scores
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Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 27 of 57
Table 9.2.1.4 Descriptive results of the change from baseline in EASI score at each 
timepoint – PP population
CD5024
Vehicle
Raw Data
Change from 
baseline
Raw Data
Change from 
baseline
Baseline
N
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
Median
xx
xx
Min;Max
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
Day 8-PP
N
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 15-PP
N
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 22-PP
N
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 29-PP
N
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 36-PP
N
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 43-LOCF
N
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
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Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 28 of 57
Table 9.2.1.5 Statistical analysis of the change from baseline EASI at each timepoint – PP 
population
CD5024
Vehicle
CD5024- Vehicle
Baseline
N
xx
xx
-
Mean
xx
xx
xx
SD
xx
xx
xx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
Day 8-PP
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
Day 15-PP
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
Day 22-PP
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
Day 29-PP
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
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Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 29 of 57
CD5024
Vehicle
CD5024- Vehicle
Day 36-PP
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
Day 43-PP
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
(1) p-values from the ANCOVA model include treatment, analysis center and baseline EASI scores
Table 9.2.1.6 Statistical Analysis of the percent change from baseline in EASI score at each 
timepoint – ITT-LOCF
CD5024
Vehicle
p-value
Raw Data
Percent 
change from 
baseline
Raw Data
Change from 
baseline
Baseline
N
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
Median
xx
xx
-
Min;Max
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
Day 8-LOCF
N
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
0.xxx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 15-LOCF
N
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
0.xxx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 22-LOCF
N
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
0.xxx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
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Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 30 of 57
CD5024
Vehicle
p-value
Raw Data
Percent 
change from 
baseline
Raw Data
Change from 
baseline
Day 29-LOCF
N
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
0.xxx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 36-LOCF
N
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
0.xxx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 43-LOCF
N
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
0.xxx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
(1) p-values based on CMH test stratified by analysis center
Table 9.2.1.7 Statistical Analysis results of the percent change from baseline in EASI score 
at each timepoint – PP
CD5024
Vehicle
p-value
Raw Data
Percent 
change from 
baseline
Raw Data
Change from 
baseline
Baseline
N
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
Median
xx
xx
-
Min;Max
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
Day 8-PP
N
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
0.xxx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 15-PP
N
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
0.xxx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
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Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 31 of 57
CD5024
Vehicle
p-value
Raw Data
Percent 
change from 
baseline
Raw Data
Change from 
baseline
Day 22-PP
N
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
0.xxx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 29-PP
N
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
0.xxx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 36-PP
N
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
0.xxx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 43-PP
N
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
0.xxx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
(1) p-values based on CMH test stratified by analysis center
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Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 32 of 57
9.2.2
Secondary efficacy endpoints
Table 9.2.2.1 Distribution of Investigator Global Assessment by visit –ITT LOCF
CD5024
Vehicle
p-value
Baseline
N (%)
xx
xx
3-Moderate
xx (xx.x%)
xx (xx.x%)
Day 8-LOCF
N (%)
xx
xx
0.xxx
0-Clear
xx (xx.x%)
xx (xx.x%)
1-Almost clear
xx (xx.x%)
xx (xx.x%)
2-Mild
xx (xx.x%)
xx (xx.x%)
3-Moderate
xx (xx.x%)
xx (xx.x%)
4-Severe
xx (xx.x%)
xx (xx.x%)
Day 15-LOCF
N (%)
xx
xx
0.xxx
0-Clear
xx (xx.x%)
xx (xx.x%)
1-Almost clear
xx (xx.x%)
xx (xx.x%)
2-Mild
xx (xx.x%)
xx (xx.x%)
3-Moderate
xx (xx.x%)
xx (xx.x%)
4-Severe
xx (xx.x%)
xx (xx.x%)
Day 22-LOCF
N (%)
xx
xx
0.xxx
0-Clear
xx (xx.x%)
xx (xx.x%)
1-Almost clear
xx (xx.x%)
xx (xx.x%)
2-Mild
xx (xx.x%)
xx (xx.x%)
3-Moderate
xx (xx.x%)
xx (xx.x%)
4-Severe
xx (xx.x%)
xx (xx.x%)
Day 29-LOCF
N (%)
xx
xx
0.xxx
0-Clear
xx (xx.x%)
xx (xx.x%)
1-Almost clear
xx (xx.x%)
xx (xx.x%)
2-Mild
xx (xx.x%)
xx (xx.x%)
3-Moderate
xx (xx.x%)
xx (xx.x%)
4-Severe
xx (xx.x%)
xx (xx.x%)
Day 36-LOCF
N (%)
xx
xx
0.xxx
0-Clear
xx (xx.x%)
xx (xx.x%)
1-Almost clear
xx (xx.x%)
xx (xx.x%)
2-Mild
xx (xx.x%)
xx (xx.x%)
3-Moderate
xx (xx.x%)
xx (xx.x%)
4-Severe
xx (xx.x%)
xx (xx.x%)
Day 43-LOCF
N (%)
xx
xx
0.xxx
0-Clear
xx (xx.x%)
xx (xx.x%)
1-Almost clear
xx (xx.x%)
xx (xx.x%)
2-Mild
xx (xx.x%)
xx (xx.x%)
3-Moderate
xx (xx.x%)
xx (xx.x%)
4-Severe
xx (xx.x%)
xx (xx.x%)
(1) p-values based on CMH test stratified by analysis center
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Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 33 of 57
Table 9.2.2.2 Distribution of Investigator Global Assessment by visit – PP
CD5024
Vehicle
p-value
Baseline
N (%)
xx
xx
3-Moderate
xx (xx.x%)
xx (xx.x%)
Day 8
N (%)
xx
xx
0.xxx
0-Clear
xx (xx.x%)
xx (xx.x%)
1-Almost clear
xx (xx.x%)
xx (xx.x%)
2-Mild
xx (xx.x%)
xx (xx.x%)
3-Moderate
xx (xx.x%)
xx (xx.x%)
4-Severe
xx (xx.x%)
xx (xx.x%)
Day 15
N (%)
xx
xx
0.xxx
0-Clear
xx (xx.x%)
xx (xx.x%)
1-Almost clear
xx (xx.x%)
xx (xx.x%)
2-Mild
xx (xx.x%)
xx (xx.x%)
3-Moderate
xx (xx.x%)
xx (xx.x%)
4-Severe
xx (xx.x%)
xx (xx.x%)
Day 22
N (%)
xx
xx
0.xxx
0-Clear
xx (xx.x%)
xx (xx.x%)
1-Almost clear
xx (xx.x%)
xx (xx.x%)
2-Mild
xx (xx.x%)
xx (xx.x%)
3-Moderate
xx (xx.x%)
xx (xx.x%)
4-Severe
xx (xx.x%)
xx (xx.x%)
Day 29
N (%)
xx
xx
0.xxx
0-Clear
xx (xx.x%)
xx (xx.x%)
1-Almost clear
xx (xx.x%)
xx (xx.x%)
2-Mild
xx (xx.x%)
xx (xx.x%)
3-Moderate
xx (xx.x%)
xx (xx.x%)
4-Severe
xx (xx.x%)
xx (xx.x%)
Day 36
N (%)
xx
xx
0.xxx
0-Clear
xx (xx.x%)
xx (xx.x%)
1-Almost clear
xx (xx.x%)
xx (xx.x%)
2-Mild
xx (xx.x%)
xx (xx.x%)
3-Moderate
xx (xx.x%)
xx (xx.x%)
4-Severe
xx (xx.x%)
xx (xx.x%)
Day 43
N (%)
xx
xx
0.xxx
0-Clear
xx (xx.x%)
xx (xx.x%)
1-Almost clear
xx (xx.x%)
xx (xx.x%)
2-Mild
xx (xx.x%)
xx (xx.x%)
3-Moderate
xx (xx.x%)
xx (xx.x%)
4-Severe
xx (xx.x%)
xx (xx.x%)
(1) p-values based on CMH test stratified by analysis center
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Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 34 of 57
Table 9.2.2.3 Summary of IGA Success - ITT LOCF
CD5024
Vehicle
p-value
Baseline
N (%)
xx
xx
3-Moderate
xx (xx.x%)
xx (xx.x%)
Day 8
N (%)
xx
xx
0.xxx
Success
xx (xx.x%)
xx (xx.x%)
Failure
xx (xx.x%)
xx (xx.x%)
Day 15
N (%)
xx
xx
0.xxx
Success
xx (xx.x%)
xx (xx.x%)
Failure
xx (xx.x%)
xx (xx.x%)
Day 22
N (%)
xx
xx
0.xxx
Success
xx (xx.x%)
xx (xx.x%)
Failure
xx (xx.x%)
xx (xx.x%)
Day 29
N (%)
xx
xx
0.xxx
Success
xx (xx.x%)
xx (xx.x%)
Failure
xx (xx.x%)
xx (xx.x%)
Day 36
N (%)
xx
xx
0.xxx
Success
xx (xx.x%)
xx (xx.x%)
Failure
xx (xx.x%)
xx (xx.x%)
Day 43
N (%)
xx
xx
0.xxx
Success
xx (xx.x%)
xx (xx.x%)
Failure
xx (xx.x%)
xx (xx.x%)
(1) p-values based on CMH test stratified by analysis center
Table 9.2.2.4 Summary of IGA Success - PP
Table 9.2.2.5 Distribution of the Hand Investigator Global Assessment by visit –ITT LOCF
Same as for IGA
Table 9.2.2.6 Distribution of the Hand Investigator Global Assessment by visit –PP
Same as for IGA
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Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 35 of 57
Table 9.2.2.7 Descriptive results of the TSS at each timepoint – ITT-LOCF
CD5024
Vehicle
Raw Data Change from 
baseline
Percent 
change from 
baseline
Raw Data
Change from 
baseline
Percent 
change from 
baseline
Baseline
N
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
Median
xx
xx
Min;Max
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
Day 8-LOCF
N
xx
xx
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 15-LOCF
N
xx
xx
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 22-LOCF
N
xx
xx
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 29-LOCF
N
xx
xx
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 36-LOCF
N
xx
xx
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 43-LOCF
N
xx
xx
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 36 of 57
Table 9.2.2.8 Statistical analysis of the percent change from baseline of the TSS at each 
timepoint – ITT-LOCF
CD5024
Vehicle
CD5024- Vehicle
Baseline
N
xx
xx
-
Mean
xx
xx
xx
SD
xx
xx
xx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
Day 8-LOCF
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
Day 15-LOCF
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
Day 22-LOCF
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
Day 29-LOCF
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
Day 36-LOCF
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 37 of 57
CD5024
Vehicle
CD5024- Vehicle
Day 43-LOCF
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
(1) p-values from the ANOVA model including treatment and analysis center effects
Table 9.2.2.9 Descriptive results of the TSS at each timepoint – PP population
Table 9.2.2.10 Statistical analysis of the percent change from baseline of the TSS at each 
timepoint – PP
Table 9.2.2.11 Descriptive results of the Modified Objective SCORAD at each timepoint – ITT 
population
CD5024
Vehicle
Raw Data Change from 
baseline
Percent 
change from 
baseline
Raw Data
Change from 
baseline
Percent 
change from 
baseline
Baseline
N
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
Median
xx
xx
Min;Max
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
Day 8-LOCF
N
xx
xx
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 15-LOCF
N
xx
xx
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 22-LOCF
N
xx
xx
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 38 of 57
CD5024
Vehicle
Raw Data Change from 
baseline
Percent 
change from 
baseline
Raw Data
Change from 
baseline
Percent 
change from 
baseline
Day 29-LOCF
N
xx
xx
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 36-LOCF
N
xx
xx
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Day 43-LOCF
N
xx
xx
xx
xx
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Table 9.2.2.12 Statistical analysis of the percent change from baseline of the Modified 
Objective SCORAD at each timepoint – ITT-LOCF
CD5024
Vehicle
CD5024- Vehicle
Baseline
N
xx
xx
-
Mean
xx
xx
xx
SD
xx
xx
xx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
Day 8-LOCF
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
Day 15-LOCF
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 39 of 57
CD5024
Vehicle
CD5024- Vehicle
Day 22-LOCF
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
Day 29-LOCF
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
Day 36-LOCF
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
Day 43-LOCF
N
xx
xx
-
LS-Mean
xx
xx
xx
SE
xx
xx
xx
p-value (1)
xx
xx
0.xxx
Lower bound 95%CI
xx
xx
xx
Upper bound 95%CI
xx
xx
xx
(1) p-values from the ANOVA model including treatment and analysis center effects
Table 9.2.2.13 Descriptive results of the Modified Objective SCORAD at each timepoint –
PP population
Table 9.2.2.14 Statistical analysis of the percent change from baseline of the Modified 
Objective SCORAD at each timepoint – PP
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 40 of 57
Table 9.2.2.15 Distribution of Erythema score by visit –ITT LOCF
CD5024
Vehicle
p-value
Baseline
N (%)
xx
xx
0-Clear
xx (xx.x%)
xx (xx.x%)
1-Almost clear
xx (xx.x%)
xx (xx.x%)
2-Mild
xx (xx.x%)
xx (xx.x%)
3-Moderate
xx (xx.x%)
xx (xx.x%)
4-Severe
xx (xx.x%)
xx (xx.x%)
Day 8-LOCF
N (%)
xx
xx
0.xxx
0-Clear
xx (xx.x%)
xx (xx.x%)
1-Almost clear
xx (xx.x%)
xx (xx.x%)
2-Mild
xx (xx.x%)
xx (xx.x%)
3-Moderate
xx (xx.x%)
xx (xx.x%)
4-Severe
xx (xx.x%)
xx (xx.x%)
Day 15-LOCF
N (%)
xx
xx
0.xxx
0-Clear
xx (xx.x%)
xx (xx.x%)
1-Almost clear
xx (xx.x%)
xx (xx.x%)
2-Mild
xx (xx.x%)
xx (xx.x%)
3-Moderate
xx (xx.x%)
xx (xx.x%)
4-Severe
xx (xx.x%)
xx (xx.x%)
Day 22-LOCF
N (%)
xx
xx
0.xxx
0-Clear
xx (xx.x%)
xx (xx.x%)
1-Almost clear
xx (xx.x%)
xx (xx.x%)
2-Mild
xx (xx.x%)
xx (xx.x%)
3-Moderate
xx (xx.x%)
xx (xx.x%)
4-Severe
xx (xx.x%)
xx (xx.x%)
Day 29-LOCF
N (%)
xx
xx
0.xxx
0-Clear
xx (xx.x%)
xx (xx.x%)
1-Almost clear
xx (xx.x%)
xx (xx.x%)
2-Mild
xx (xx.x%)
xx (xx.x%)
3-Moderate
xx (xx.x%)
xx (xx.x%)
4-Severe
xx (xx.x%)
xx (xx.x%)
Day 36-LOCF
N (%)
xx
xx
0.xxx
0-Clear
xx (xx.x%)
xx (xx.x%)
1-Almost clear
xx (xx.x%)
xx (xx.x%)
2-Mild
xx (xx.x%)
xx (xx.x%)
3-Moderate
xx (xx.x%)
xx (xx.x%)
4-Severe
xx (xx.x%)
xx (xx.x%)
Day 43-LOCF
N (%)
xx
xx
0.xxx
0-Clear
xx (xx.x%)
xx (xx.x%)
1-Almost clear
xx (xx.x%)
xx (xx.x%)
2-Mild
xx (xx.x%)
xx (xx.x%)
3-Moderate
xx (xx.x%)
xx (xx.x%)
4-Severe
xx (xx.x%)
xx (xx.x%)
(1) p-values based on CMH test stratified by analysis center, for the change from baseline
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 41 of 57
Table 9.2.2.16 Distribution of Erythema score by visit – PP
Table 9.2.2.17 Distribution of Induration/Papulation score by visit – ITT LOCF
Table 9.2.2.18 Distribution of Induration/Papulation score by visit – PP
Table 9.2.2.19 Distribution of Oozing/Crusting score by visit – ITT LOCF
Table 9.2.2.20 Distribution of Oozing/Crusting score by visit – PP
Table 9.2.2.21 Distribution of Excoriation score by visit – ITT LOCF
Table 9.2.2.22 Distribution of Excoriation score by visit – PP
Table 9.2.2.23 Distribution of Lichenification score by visit – ITT LOCF
Table 9.2.2.24 Distribution of Lichenification score by visit – PP
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 42 of 57
Table 9.2.2.25 Descriptive results of the weekly average NRS at each timepoint – ITT 
population
CD5024
Vehicle
p-value(1)
Raw Data
Change from 
baseline
Raw Data
Change from 
baseline
Baseline
N
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
Median
xx
xx
Min;Max
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
Week 1 - LOCF
N
xx
xx
xx
xx
0.xxx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Week 2-LOCF
N
xx
xx
xx
xx
0.xxx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Week 3 -LOCF
N
xx
xx
xx
xx
0.xxx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Week 4 -LOCF
N
xx
xx
xx
xx
0.xxx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Week 5 -LOCF
N
xx
xx
xx
xx
0.xxx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Week 6 -LOCF
N
xx
xx
xx
xx
0.xxx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
(1) p-values based on CMH test stratified by analysis center Baseline is the mean of the values collected from Day -1 to Day -3
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 43 of 57
Table 9.2.2.26 Descriptive results of the weekly average NRS at each timepoint – PP population
Table 9.2.2.27 Descriptive results of the VRS at each timepoint – ITT population
CD5024
Vehicle
p-value(1)
Raw Data
Change from 
baseline
Raw Data
Change from 
baseline
Baseline
N
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
Median
xx
xx
Min;Max
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
Day 43 -LOCF
N
xx
xx
xx
xx
0.xxx
Mean±SD
xx.x ±xx
xx.x ±xx
xx.x ±xx
xx.x ±xx
Median
xx
xx
xx
xx
Min;Max
xx ; xx
xx ; xx
xx ; xx
xx ; xx
Q1;Q3
xx ; xx
xx ; xx
xx ; xx
xx ; xx
(1) p-values based on CMH test stratified by analysis center
Table 9.2.2.28 Descriptive results of the VRS at each timepoint – PP population
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 44 of 57
9.2.3
Subgroup analyses
Table 9.2.3.1 Descriptive results of EASI at each timepoint broken down by IgE– ITT 
population
IgE<X
IgE>=X
CD5024
Vehicle
CD5024
Vehicle
Raw 
Data
Change 
from 
baselin
e
Percent 
change 
from 
baselin
e
Raw 
Data
Change 
from 
baselin
e
Percent 
change 
from 
baselin
e
Raw 
Data
Change 
from 
baselin
e
Percent 
change 
from 
baselin
e
Raw 
Data
Change 
from 
baselin
e
Percent 
change 
from 
baselin
e
Baselin
e
N
xx
xx
xx
Mean±SD xx.x
±xx
xx.x
±xx
xx.x
±xx
Median
xx
xx
xx
Min;Max
xx ; 
xx
xx ; xx
xx ; 
xx
Q1;Q3
xx ; 
xx
xx ; xx
xx ; 
xx
Day 8-
LOCF
N
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
Mean±SD xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
Median
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
Min;Max
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
Q1;Q3
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
Day 15-
LOCF
N
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
Mean±SD xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
Median
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
Min;Max
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
Q1;Q3
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
Day 22-
LOCF
N
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
Mean±SD xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
Median
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
Min;Max
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
Q1;Q3
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 45 of 57
IgE<X
IgE>=X
CD5024
Vehicle
CD5024
Vehicle
Day 29-
LOCF
N
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
Mean±SD xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
Median
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
Min;Max
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
Q1;Q3
xx ;
xx ; xx
xx ; xx
xx ;
xx ; xx
xx ; xx
xx ;
xx ; xx
xx ; xx
xx ;
xx ; xx
xx ; xx
xx
xx
xx
xx
Day 36-
LOCF
N
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
Mean±SD xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
Median
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
Min;Max
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
Q1;Q3
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
Day 43-
LOCF
N
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
Mean±SD xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
xx.x
±xx
Median
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
Min;Max
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
Q1;Q3
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
xx ; 
xx
xx ; xx
xx ; xx
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 46 of 57
9.3
Safety analysis
9.3.1
Extent of exposure
Table 9.3.1.1 Treatment applications- Safety population
CD5024
Vehicle
Treatment duration (in days)
N
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
Median
xx
xx
Min;Max
xx ; xx
xx ; xx
Table 9.3.1.2 Quantity of product used (g)
CD5024
Vehicle
Total medication used (g)
N
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
Median
xx
xx
Min;Max
xx ; xx
xx ; xx
Daily medication used (g/day)
N
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
Median
xx
xx
Min;Max
xx ; xx
xx ; xx
Table 9.3.1.3 Quantity of product applied in Fingertips unit (FTU)
CD5024
Vehicle
Total number of fingertips (FTU)
N
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
Median
xx
xx
Min;Max
xx ; xx
xx ; xx
Daily fingertips (FTU/day)
N
xx
xx
Mean±SD
xx.x ±xx
xx.x ±xx
Median
xx
xx
Min;Max
xx ; xx
xx ; xx
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Pr ot o c ol N o: R D. 0 3. S P R. 1 0 9 6 9 6
St atisti c al A n al ysis Pl a n
Pa ge 4 7 of 5 7
C O N FI D E N TI A L  G A L D E R M A  
2 1- J ul- 2 0 1 7
I nt er n all y A p pr o v e d
C CI


Pr ot o c ol N o: R D. 0 3. S P R. 1 0 9 6 9 6
St atisti c al A n al ysis Pl a n
Pa ge 4 8 of 5 7
C O N FI D E N TI A L  G A L D E R M A  
2 1- J ul- 2 0 1 7
I nt er n all y A p pr o v e d
C CI


Pr ot o c ol N o: R D. 0 3. S P R. 1 0 9 6 9 6
St atisti c al A n al ysis Pl a n
Pa ge 4 9 of 5 7
C O N FI D E N TI A L  G A L D E R M A  
2 1- J ul- 2 0 1 7
I nt er n all y A p pr o v e d
C CI


Pr ot o c ol N o: R D. 0 3. S P R. 1 0 9 6 9 6
St atisti c al A n al ysis Pl a n
Pa ge 5 0 of 5 7
9. 3. 3
L a b or at or y p ar a meters
9. 3. 3. 1
Bl o o d c he mistry
T a ble 9. 3. 3. 1. 1 Bl o o d c he mistr y s hift t a ble
B a s eli n e
C D 5 0 2 4
V e hi cl e
L o w
N or m al
Hi g h
Mi s si n g
L o w
N or m al
Hi g h
Mi s si n g
D a y 2 2
P ar a m et er # 1
L o w
-
x ( x. x)
- 
- 
- 
- 
- 
-
N or m al
-
x ( x. x)
- 
- 
-
x ( x. x)
- 
-
Hi g h
-
x ( x. x)
- 
- 
-
x ( x. x)
- 
-
Mi s si n g
- 
- 
- 
- 
-
x ( x. x)
- 
-
P ar a m et er # 2
L o w
-
x ( x. x)
- 
- 
-
x ( x. x)
- 
-
N or m al
-
x ( x. x)
- 
- 
-
x ( x. x)
- 
-
Hi g h
-
x ( x. x)
- 
- 
-
x ( x. x)
- 
-
Mi s si n g
- 
- 
- 
- 
- 
- 
- 
-
…
…
D a y 4 3/ e arl y 
T er mi n ati o n
P ar a m et er # 1
L o w
- 
- 
- 
- 
- 
- 
- 
-
N or m al
-
x ( x. x)
- 
- 
-
x ( x. x)
- 
-
Hi g h
-
x ( x. x)
- 
- 
-
x ( x. x)
- 
-
Mi s si n g
-
x ( x. x)
- 
- 
-
x ( x. x)
- 
-
P ar a m et er # 2
L o w
-
x ( x. x)
- 
- 
-
x ( x. x)
- 
-
N or m al
-
x ( x. x)
- 
- 
-
x ( x. x)
- 
-
Hi g h
-
x ( x. x)
- 
- 
-
x ( x. x) 
- 
-
Mi s si n g
- 
- 
- 
- 
- 
- 
- 
-
…
…
- 
- 
-
- 
-
C O N FI D E N TI A L  G A L D E R M A  
2 1- J ul- 2 0 1 7
I nt er n all y A p pr o v e d
C CI


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 51 of 57
Table 9.3.3.1.2 Blood chemistry parameter over time
CD5024
Vehicle
Raw data
Change
Raw data
Change
Parameter#
1
Baseline
N
xx
xx
Mean±SD
x.xx±x.xx
x.xx±x.xx
Median
x.xx
x.xx
Min;Max
x.xx;x.xx
x.xx;x.xx
Day 22
N
xx
xx
xx
xx
Mean±SD
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
Median
x.xx
x.xx
x.xx
x.xx
Min;Max
x.xx;x.xx
-x.xx;x.xx
x.xx;x.xx
-x.xx;x.xx
Day 43 / Early Termination
N
xx
xx
xx
xx
Mean±SD
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
Median
x.xx
x.xx
x.xx
x.xx
Min;Max
x.xx;x.xx
-x.xx;x.xx
x.xx;x.xx
-x.xx;x.xx
Parameter#
2
Baseline
N
xx
xx
Mean±SD
x.xx±x.xx
x.xx±x.xx
Median
x.xx
x.xx
Min;Max
x.xx;x.xx
x.xx;x.xx
Day 22
N
xx
xx
xx
xx
Mean±SD
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
Median
x.xx
x.xx
x.xx
x.xx
Min;Max
x.xx;x.xx
-x.xx;x.xx
x.xx;x.xx
-x.xx;x.xx
Day 43 / Early Termination
N
xx
xx
xx
xx
Mean±SD
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
Median
x.xx
x.xx
x.xx
x.xx
Min;Max
x.xx;x.xx
-x.xx;x.xx
x.xx;x.xx
-x.xx;x.xx
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 52 of 57
9.3.3.2
Hematology
Table 9.3.3.2.1 Hematology shift table
Baseline
CD5024
Vehicle
Low
Normal
High
Missing
Low
Normal
High
Missing
Day 22
Parameter#1 
(unit)
Low
-
x (x.x)
-
-
-
x (x.x)
-
-
Normal
-
x (x.x)
-
-
-
x (x.x)
-
-
High
-
x (x.x)
-
-
-
x (x.x)
-
-
Missing
-
-
-
-
-
-
-
Parameter#2 
(unit)
Low
-
x (x.x)
-
-
-
x (x.x)
-
-
Normal
-
x (x.x)
-
-
-
x (x.x)
-
-
High
-
x (x.x)
-
-
-
x (x.x)
-
-
Missing
-
-
-
-
-
-
-
-
…
…
Day 43/Early 
Termination
Parameter#1 
(unit)
Low
-
-x (x.x)
-
-
-
x (x.x)
-
-
Normal
-
x (x.x)
-
-
-
x (x.x)
-
-
High
-
x (x.x)
-
-
-
x (x.x)
-
-
Missing
-
-
-
-
-
-
Parameter#2 
(unit)
Low
-
x (x.x)
-
-
-
x (x.x)
-
-
Normal
-
x (x.x)
-
-
-
x (x.x)
-
-
High
-
x (x.x)
-
-
-
x (x.x)
-
-
Missing
-
-
-
-
-
-
-
-
…
…
-
-
-
-
-
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 53 of 57
Table 9.3.3.2.2 Descriptive analysis for Creatinine Clearance
CD5024
Vehicle
Baseline
> 90 mL/min/1.73m²
x (x.x)
x (x.x)
60-89  mL/min/1.73m²
x (x.x)
x (x.x)
30-59  mL/min/1.73m²
x (x.x)
x (x.x)
15-29  mL/min/1.73m²
x (x.x)
x (x.x)
<15 mL/min/1.73m²
x (x.x)
x (x.x)
Day 22
> 90 mL/min/1.73m²
x (x.x)
x (x.x)
60-89  mL/min/1.73m²
x (x.x)
x (x.x)
30-59  mL/min/1.73m²
x (x.x)
x (x.x)
15-29  mL/min/1.73m²
x (x.x)
x (x.x)
<15 mL/min/1.73m²
x (x.x)
x (x.x)
Day 43/Early Termination
> 90 mL/min/1.73m²
x (x.x)
x (x.x)
60-89  mL/min/1.73m²
x (x.x)
x (x.x)
…
Table 9.3.3.2.3 Hematology parameter over time
CD5024
Vehicle
Raw data
Change
Raw data
Change
Parameter#1
Baseline
N
xx
xx
Mean±SD
x.xx±x.xx
x.xx±x.xx
Median
x.xx
x.xx
Min;Max
x.xx;x.xx
x.xx;x.xx
Day 22
N
xx
xx
xx
xx
Mean±SD
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
Median
x.xx
x.xx
x.xx
x.xx
Min;Max
x.xx;x.xx
-x.xx;x.xx
x.xx;x.xx
-x.xx;x.xx
Day 43 / Early Termination
N
xx
xx
xx
xx
Mean±SD
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
Median
x.xx
x.xx
x.xx
x.xx
Min;Max
x.xx;x.xx
-x.xx;x.xx
x.xx;x.xx
-x.xx;x.xx
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 54 of 57
CD5024
Vehicle
Raw data
Change
Raw data
Change
Parameter#2
Baseline
N
xx
xx
Mean±SD
x.xx±x.xx
x.xx±x.xx
Median
x.xx
x.xx
Min;Max
x.xx;x.xx
x.xx;x.xx
Day 22
N
xx
xx
xx
xx
Mean±SD
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
Median
x.xx
x.xx
x.xx
x.xx
Min;Max
x.xx;x.xx
-x.xx;x.xx
x.xx;x.xx
-x.xx;x.xx
Day 43 / Early Termination
N
xx
xx
xx
xx
Mean±SD
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
Median
x.xx
x.xx
x.xx
x.xx
Min;Max
x.xx;x.xx
-x.xx;x.xx
x.xx;x.xx
-x.xx;x.xx
9.3.3.3
Coagulation
Table 9.3.3.3.1 Coagulation shift table
Baseline
CD5024
Vehicle
Low
Normal
High
Missing
Low
Normal
High
Missing
Day 22
Prothrombin 
Ratio
Low
-
x (x.x)
-
-
-
x (x.x)
-
-
Normal
-
x (x.x)
-
-
-
x (x.x)
-
-
High
-
x (x.x)
-
-
-
x (x.x)
-
-
Missing
-
-
-
-
-
-
Day 43/Early 
Termination
Prothrombin 
Ratio
Low
-
x (x.x)-
-
-
-
x (x.x)
-
-
Normal
-
x (x.x)
-
-
-
x (x.x)
-
-
High
-
x (x.x)
-
-
-
x (x.x)
-
-
Missing
-
-
-
-
-
-
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 55 of 57
Table 9.3.3.3.2 Coagulation parameter over time
CD5024
Vehicle
Raw data
Change
Raw data
Change
Prothrombin 
Ratio
Baseline
N
xx
xx
Mean±SD
x.xx±x.xx
x.xx±x.xx
Median
x.xx
x.xx
Min;Max
x.xx;x.xx
x.xx;x.xx
Day 22
N
xx
xx
xx
xx
Mean±SD
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
Median
x.xx
x.xx
x.xx
x.xx
Min;Max
x.xx;x.xx
-x.xx;x.xx
x.xx;x.xx
-x.xx;x.xx
Day 43 / Early Termination
N
xx
xx
xx
xx
Mean±SD
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
Median
x.xx
x.xx
x.xx
x.xx
Min;Max
x.xx;x.xx
-x.xx;x.xx
x.xx;x.xx
-x.xx;x.xx
9.3.4
Vital Sign and physical examination and other information related to safety
Table 9.3.4.1 Descriptive results of vital signs
CD5024
Vehicle
Systolic 
blood 
pressure 
(mmHg)
Diastolic 
blood 
pressure 
(mmHg)
Pulse rate 
(bpm)
Systolic 
blood 
pressure 
(mmHg)
Diastolic 
blood 
pressure 
(mmHg)
Pulse rate 
(bpm)
Baseline
N
xx
xx
xx
xx
xx
xx
Mean±SD
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
Median
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Min;Max
x.xx;x.xx
x.xx;x.xx
x.xx;x.xx
x.xx;x.xx
x.xx;x.xx
x.xx;x.xx
….
N
xx
xx
xx
xx
xx
xx
Mean±SD
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
Median
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Min;Max
x.xx;x.xx
x.xx;x.xx
x.xx;x.xx
x.xx;x.xx
x.xx;x.xx
x.xx;x.xx
Day 54/Early 
termination
N
xx
xx
xx
xx
xx
xx
Mean±SD
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
x.xx±x.xx
Median
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Min;Max
x.xx;x.xx
x.xx;x.xx
x.xx;x.xx
x.xx;x.xx
x.xx;x.xx
x.xx;x.xx
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Protocol No: RD.03.SPR.109696
Statistical Analysis Plan
Page 56 of 57
Table 9.3.4.2 Descriptive results of physical examination
CD5024
Vehicle
Baseline
N (%)
xx
xx
Normal Physical Examination
xx (xx.x)
xx (xx.x)
Day 15
N (%)
xx
xx
Normal Physical Examination
xx (xx.x)
xx (xx.x)
Ex #1 Neurological Function
x (x.x)
x (x.x)
Ex #2 Skin
x (x.x)
x (x.x)
…
Day 29
N (%)
xx
xx
Normal Physical Examination
xx (xx.x)
xx (xx.x)
Ex #1 Neurological Function
x (x.x)
x (x.x)
Ex #2 Skin
…
x (x.x)
x (x.x)
Day 43
N (%)
xx
xx
Normal Physical Examination
xx (xx.x)
xx (xx.x)
Ex #1 Neurological Function
x (x.x)
x (x.x)
Ex #2 Skin
x (x.x)
x (x.x)
…
Day 54/Early termination
N (%)
xx
xx
Normal Physical Examination
xx (xx.x)
xx (xx.x)
Ex #1 Neurological Function
x (x.x)
x (x.x)
Ex #2 Skin
x (x.x)
x (x.x)
…
Table 9.3.4.3 Descriptive results of ECG
CD5024
Vehicle
Baseline
N (%)
xx
xx
Normal
xx (xx.x)
xx (xx.x)
Abnormal
xx (xx.x)
xx (xx.x)
Day 43/Early termination
N (%)
xx
xx
Normal
xx (xx.x)
xx (xx.x)
Abnormal
x (x.x)
x (x.x)
CONFIDENTIAL GALDERMA
 
21-Jul-2017
Internally Approved


Pr ot o c ol N o: R D. 0 3. S P R. 1 0 9 6 9 6
St atisti c al A n al ysis Pl a n
Pa ge 5 7 of 5 7
C O N FI D E N TI A L  G A L D E R M A  
2 1- J ul- 2 0 1 7
I nt er n all y A p pr o v e d
C CI