A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Of EN3835 In The Treatment Of Edematous Fibrosclerotic Panniculopathy (Cellulite)
Phase: PHASE3
Conditions: Edematous Fibrosclerotic Panniculopathy (Cellulite)
Sponsor: Endo Pharmaceuticals



EN3835-303 Protocol Amendment 3 
05-Jun-2018 
Endo Pharmaceuticals Inc. 
Page 3 
 
 
 
Section 
Original Text 
Revised Text 
17.2.4 Per-
Protocol (PP) 
Population 
The PP population is defined as the mITT 
subjects without any of the following :  
• Placebo-assigned subject receives EN3835 
treatment 
• EN3835-assigned subject receives placebo 
treatment only throughout study 
• Any subject receives protocol-prohibited 
medications 
• Subject lacking PR-PCSS and/or CR-PCSS 
assessment at Day 71 
• Any major protocol deviation that is 
deemed as impact subject efficacy 
The PP population is defined as the mITT 
subjects without any of the following :  
• Placebo randomized subject who receives 
EN3835 treatment. 
• EN3835 randomized subject who receives 
placebo treatment only throughout study. 
• Any subject who uses protocol-prohibited 
medications. 
• Subject missing PR-PCSS and/or 
CR-PCSS assessment at Day 71. 
• Subject with a buttock not receiving all 
three treatment sessions without medical 
reasons (e.g., adverse events or CR-PCSS 
rated as zero (0)). 
• Subject who did not meet all inclusion and 
exclusion criteria.  
Amendment 2 was incorporated into the protocol on January 18, 2018. The major reasons for 
this amendment are revising the primary efficacy variable from at least one buttock to a 
randomly selected target buttock, revising key secondary endpoints, and adding an additional 
efficacy assessment. 
Section 
Original Text 
Revised Text 
4 Synopsis, 
Study Period 
Estimated date first subject enrolled: Feb-2018 
Estimated date last subject completed: 
Sep-2018 
Estimated date first subject enrolled: Feb-2018 
Estimated date last subject completed: 
Oct-2018 
4 Synopsis, 
Study Design 
Added text 
Of the two assigned eligible buttocks, one 
buttock will be randomly selected as the target 
buttock for the primary efficacy endpoint. The 
other (remaining) buttock will be considered 
the non-target buttock. Subjects, investigators, 
site personnel, and Endo personnel will be 
blinded to the identification of the target and 
the non-target buttocks. 
At Day 1, the subject will complete a Patient 
Reported Cellulite Impact Scale (PR-CIS) 
assessment. 
At Day 1, the subject will complete a Patient 
Reported Cellulite Impact Scale (PR-CIS) 
assessment and a Subject Self-Rating Scale 
(SSRS) assessment. 
4 Synopsis, 
Diagnosis and 
Inclusion/Ex-
clusion Criteria, 
Exclusion 
Criteria 
13. Was a subject in a previous cellulite 
clinical trial of collagenase clostridium 
histolyticum (CCH): AUX-CC-830, 
AUX-CC-831, EN3835-102, 
EN3835-104, EN3835-201, and/or 
EN3835-202 
13 Was a subject in a previous cellulite 
clinical trial of collagenase clostridium 
histolyticum (CCH): AUX-CC-830, 
AUX-CC-831, EN3835-102, 
EN3835-104, EN3835-201, EN3835-202, 
and/or EN3835-205 

EN3835-303 Protocol Amendment 3 
05-Jun-2018 
Endo Pharmaceuticals Inc. 
Page 4 
 
 
 
Section 
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Revised Text 
4 Synopsis, 
Criteria for 
Evaluation, 
Efficacy 
• Subject using PR-PCSS while viewing 
digital image of the left buttock: 5-level 
scale ranging from 0 (no cellulite) to 4 
(severe cellulite) (Day 1 (Baseline) and 
Days 22, 43, and 71) for the left buttock 
• Subject using PR-PCSS while viewing 
digital image of the right buttock: 5-level 
scale ranging from 0 (no cellulite) to 4 
(severe cellulite) (Day 1 (Baseline) and 
Days 22, 43, and 71) for the right buttock 
• Investigator using the CR-PCSS by live 
assessment: 5-level scale ranging from 0 
(no cellulite) to 4 (severe cellulite) (Day 1 
(Baseline) and Days 22, 43, and 71) for the 
left buttock 
• Investigator using the CR-PCSS by live 
assessment: 5-level scale ranging from 0 
(no cellulite) to 4 (severe cellulite) (Day 1 
(Baseline) and Days 22, 43, and 71) for the 
right buttock 
• Investigator Global Aesthetic 
Improvement Scale (I-GAIS): 7-level scale 
ranging from 3 (very much improved) to 
−3 (very much worse) (Days 22, 43, and 
71) for the left buttock 
• Investigator Global Aesthetic 
Improvement Scale (I-GAIS): 7-level scale 
ranging from 3 (very much improved) to 
−3 (very much worse) (Days 22, 43, and 
71) for the right buttock 
• Subject Global Aesthetic Improvement 
Scale (S-GAIS): 7-level scale ranging from 
3 (very much improved) to −3 (very much 
worse) (Days 22, 43, and 71) for the left 
buttock 
• Subject Global Aesthetic Improvement 
Scale (S-GAIS): 7-level scale ranging from 
3 (very much improved) to −3 (very much 
worse) (Days 22, 43, and 71) for the right 
buttock 
• Patient Reported Cellulite Impact Scale 
(PR-CIS): 6 questions with responses to 
each question consisting of a numerical 
rating scale (NRS) ranging from 0 (Not at 
all) to 10 (Extremely) 
• Subject satisfaction with cellulite treatment 
assessment: 5-level scale ranging from 2 
(very satisfied) to −2 (very dissatisfied) 
(Day 71) for both left and right buttocks 
• Subject using PR-PCSS while viewing 
digital image of the target buttock: 5-level 
scale ranging from 0 (no cellulite) to 4 
(severe cellulite) (Day 1 (Baseline) and 
Days 22, 43, and 71) for the target buttock 
• Subject using PR-PCSS while viewing 
digital image of the non-target buttock: 
5-level scale ranging from 0 (no cellulite) 
to 4 (severe cellulite) (Day 1 (Baseline) 
and Days 22, 43, and 71) for the non-target 
buttock 
• Investigator using the CR-PCSS by live 
assessment: 5-level scale ranging from 0 
(no cellulite) to 4 (severe cellulite) (Day 1 
(Baseline) and Days 22, 43, and 71) for the 
target buttock 
• Investigator using the CR-PCSS by live 
assessment: 5-level scale ranging from 0 
(no cellulite) to 4 (severe cellulite) (Day 1 
(Baseline) and Days 22, 43, and 71) for the 
non-target buttock 
• Investigator Global Aesthetic 
Improvement Scale (I-GAIS): 7-level scale 
ranging from 3 (very much improved) to 
−3 (very much worse) (Days 22, 43, and 
71) for the target buttock 
• Investigator Global Aesthetic 
Improvement Scale (I-GAIS): 7-level scale 
ranging from 3 (very much improved) to 
−3 (very much worse) (Days 22, 43, and 
71) for the non-target buttock 
• Subject Global Aesthetic Improvement 
Scale (S-GAIS): 7-level scale ranging from 
3 (very much improved) to −3 (very much 
worse) (Days 22, 43, and 71) for the target 
buttock 
• Subject Global Aesthetic Improvement 
Scale (S-GAIS): 7-level scale ranging from 
3 (very much improved) to −3 (very much 
worse) (Days 22, 43, and 71) for the non-
target buttock 
• Patient Reported Cellulite Impact Scale 
(PR-CIS): 6 questions with responses to 
each question consisting of a numerical 
rating scale (NRS) ranging from 0 (Not at 
all) to 10 (Extremely) 
• Subject Self-Rating Scale (SSRS): 7-level 
scale ranging from 0 (extremely 
dissatisfied) to 6 (extremely satisfied) 
(Day 1 (Baseline) and Day 71)  

EN3835-303 Protocol Amendment 3 
05-Jun-2018 
Endo Pharmaceuticals Inc. 
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Section 
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Revised Text 
4 Synopsis, 
Statistical 
Methods, 
Analyses, 
Analyses of 
Primary 
Endpoint 
The primary endpoint is the proportion of 
2-level composite responders at Day 71 
defined as subjects with at least one of two 
treated buttocks with: 
• an improvement in severity from baseline 
(Day 1 visit) of at least 2 levels of severity 
in the CR-PCSS as assessed live by the 
Investigator, and 
• an improvement in severity from baseline 
of at least 2 levels of severity in the 
PR-PCSS as assessed by the subject while 
viewing the digital image of the same 
buttock. 
A subject will be considered a responder if 
these criteria are met in the left buttock or 
right buttock or both buttocks in that subject. 
The primary endpoint is the proportion of 
2-level composite responders at Day 71 
defined as subjects with: 
• an improvement in severity from baseline 
(Day 1 visit) of at least 2 levels of severity 
in the CR-PCSS as assessed live by the 
Investigator of the target buttock, and 
• an improvement in severity from baseline 
of at least 2 levels of severity in the 
PR-PCSS as assessed by the subject while 
viewing the digital image of the target 
buttock. 
A subject will be considered a responder if 
these criteria are met in the randomized target 
buttock of that subject. 
4 Synopsis, 
Statistical 
Methods, 
Analyses, 
Analyses of Key 
Secondary 
Endpoints 
There will be 4 key secondary endpoints 
grouped as two families of 2 endpoints per 
family analyzed in a hierarchical order. 
There will be 8 key secondary endpoints 
grouped as three families of 2-4 endpoints per 
family analyzed in hierarchical order. 
• Family #1 – two endpoints: 
• Family #1 – four endpoints: 
− Proportion of 1-level PR-PCSS responders 
defined as subjects with ≥1-level 
improvement in PR-PCSS severity rating 
of left buttock at Day 71 compared to 
Day 1 
− Proportion of 1-level PR-PCSS responders 
defined as subjects with ≥1-level 
improvement in PR-PCSS severity rating 
of the target buttock at Day 71 compared to 
Day 1 
 
− Proportion of 1-level PR-PCSS responders 
defined as subjects with ≥1-level 
improvement in PR-PCSS severity rating 
of right buttock at Day 71 compared to 
Day 1 
− Proportion of 2-level PR-PCSS responders 
defined as subjects with ≥2-level 
improvement in PR-PCSS severity rating 
of the target buttock at Day 71 compared to 
Day 1 
 
• Family #2 – two endpoints: 
− Proportion of 1-level S-GAIS responders 
defined as subjects with ≥1-level 
improvement (improved, much improved 
or very much improved) in the S-GAIS 
assessment of left buttock at Day 71 
− Proportion of 1-level S-GAIS responders 
defined as subjects with ≥1-level 
improvement (improved, much improved 
or very much improved) in the S-GAIS 
assessment of right buttock at Day 71 
− Proportion of 1-level composite responders 
of the target buttock (defined as subjects 
with an improvement in severity from 
baseline of at least 1 level of severity in the 
CR-PCSS of the target buttock assessed 
live by the Investigator and an 
improvement of severity from baseline of 
at least 1 level of severity in the PR-PCSS 
of the target buttock) at Day 71 compared 
to Day 1 
− Proportion of 2-level composite responders 
of the non-target buttock at Day 71 
compared to Day 1 
• Family #2 – two endpoints: 
− Proportion of 1-level SSRS responders 
defined as subjects who were at least 
slightly satisfied at Day 71 (SSRS rating 
≥ 4)  
− Change from baseline (Day1) of the 
PR-CIS at Day 71 
 
 

EN3835-303 Protocol Amendment 3 
05-Jun-2018 
Endo Pharmaceuticals Inc. 
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Revised Text 
 
• Family #3 – two endpoints: 
− Proportion of 1-level S-GAIS responders 
defined as subjects with ≥1-level 
improvement (improved, much improved 
or very much improved) in the S-GAIS 
assessment of the target buttock at Day 71 
− Proportion of 2-level S-GAIS responders 
defined as subjects with ≥2-level 
improvement (much improved or very 
much improved) in the S-GAIS assessment 
of the target buttock at Day 71 
The family #1 key secondary efficacy analyses 
will be performed only if the primary efficacy 
analysis is significant at a significance level of 
p ≤ 0.05 (gatekeeping strategy). Similarly, 
family #2 key secondary efficacy analyses will 
be performed only if at least one of the key 
secondary efficacy endpoints of family #1 is 
significant at a significance level of p ≤ 0.025 
(parallel gatekeeping strategy) 
The family #1 key secondary efficacy analyses 
will be performed only if the primary efficacy 
analysis is significant at a significance level of 
p ≤ 0.05 (gatekeeping strategy). Similarly, 
family #2 key secondary efficacy analyses will 
be performed only if at least one of the key 
secondary efficacy endpoints of family #1 is 
significant at a significance level of p ≤ 0.0125 
and family #3 key secondary efficacy analyses 
will be performed only if at least one of the 
key secondary efficacy endpoints of family #2 
is significant (parallel gatekeeping strategy). 
4 Synopsis, 
Statistical 
Methods, 
Analysis, 
Supportive 
Endpoints 
• Proportion of 2-level PR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 2 levels 
of severity in the PR-PCSS) of the left 
buttock (Days 22, 43, and 71) 
• Proportion of 2-level PR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 2 levels 
of severity in the PR-PCSS) of the right 
buttock (Days 22, 43, and 71) 
• Proportion of 1-level PR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the PR-PCSS) of the left 
buttock (Days 22, 43, and 71) 
• Proportion of 1-level PR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the PR-PCSS) of the right 
buttock (Days 22, 43, and 71) 
• Proportion of 2-level PR-PCSS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the left 
buttock or right buttock or both buttocks in 
that subject. 
• Proportion of 2-level PR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 2 levels 
of severity in the PR-PCSS) of the target 
buttock (Days 22, 43, and 71) 
• Proportion of 2-level PR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 2 levels 
of severity in the PR-PCSS) of the non-
target buttock (Days 22, 43, and 71) 
• Proportion of 1-level PR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the PR-PCSS) of the target 
buttock (Days 22, 43, and 71)  
• Proportion of 1-level PR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the PR-PCSS) of the non-
target buttock (Days 22, 43, and 71) 
• Proportion of 2-level PR-PCSS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the 
target buttock or non-target buttock or both 
buttocks in that subject.  

EN3835-303 Protocol Amendment 3 
05-Jun-2018 
Endo Pharmaceuticals Inc. 
Page 8 
 
 
 
Section 
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Revised Text 
 
• Proportion of 1-level PR-PCSS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the left 
buttock or right buttock or both buttocks in 
that subject. 
• Proportion of 2-level PR-PCSS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both left and right buttocks. 
• Proportion of 1-level PR-PCSS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both left and right buttocks. 
• Proportion of 2-level CR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 2 levels 
of severity in the CR-PCSS) of the left 
buttock (Days 22, 43, and 71) 
• Proportion of 2-level CR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 2 levels 
of severity in the CR-PCSS) of the right 
buttock (Days 22, 43, and 71) 
• Proportion of 1-level CR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the CR-PCSS) of the left 
buttock (Days 22, 43, and 71) 
• Proportion of 1-level CR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the CR-PCSS) of the right 
buttock (Days 22, 43, and 71) 
• Proportion of 2-level CR-PCSS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the left 
buttock or right buttock or both buttocks in 
that subject 
• Proportion of 1-level CR-PCSS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the left 
buttock or right buttock or both buttocks in 
that subject 
• Proportion of 1-level PR-PCSS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the 
target buttock or non-target buttock or both 
buttocks in that subject. 
• Proportion of 2-level PR-PCSS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both the target and non-target 
buttocks. 
• Proportion of 1-level PR-PCSS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both the target and non-target 
buttocks. 
• Proportion of 2-level CR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 2 levels 
of severity in the CR-PCSS) of the target 
buttock (Days 22, 43, and 71) 
• Proportion of 2-level CR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 2 levels 
of severity in the CR-PCSS) of the 
non-target buttock (Days 22, 43, and 71) 
• Proportion of 1-level CR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the CR-PCSS) of the target 
buttock (Days 22, 43, and 71) 
• Proportion of 1-level CR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the CR-PCSS) of the 
non-target buttock (Days 22, 43, and 71) 
• Proportion of 2-level CR-PCSS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the 
target buttock or non-target buttock or both 
buttocks in that subject 
• Proportion of 1-level CR-PCSS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the 
target buttock or non-target buttock or both 
buttocks in that subject 

EN3835-303 Protocol Amendment 3 
05-Jun-2018 
Endo Pharmaceuticals Inc. 
Page 9 
 
 
 
Section 
Original Text 
Revised Text 
• Proportion of 2-level CR-PCSS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both left and right buttocks 
• Proportion of 1-level CR-PCSS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both left and right buttocks 
• Proportion of 1-level composite responders 
of the left buttock (defined as subjects with 
an improvement in severity from baseline 
of at least 1 level of severity in the CR-
PCSS of the left buttock assessed live by 
the Investigator and an improvement of 
severity from baseline of at least 1 level of 
severity in the PR-PCSS of that same left 
buttock) (Days 22, 43, and 71) 
• Proportion of 1-level composite responders 
of the right buttock (defined as subjects 
with an improvement in severity from 
baseline of at least 1 level of severity in the 
CR-PCSS of the right buttock assessed live 
by the Investigator and an improvement of 
severity from baseline of at least 1 level of 
severity in the PR-PCSS of that same right 
buttock) (Days 22, 43, and 71) 
• Proportion of 1-level composite responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the left 
buttock or right buttock or both buttocks in 
that subject. 
• Proportion of 1-level composite responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both left and right buttocks. 
• Proportion of 2-level composite responders 
of the left buttock (defined as subjects with 
an improvement in severity from baseline 
of at least 2 levels of severity in the CR-
PCSS of the left buttock assessed live by 
the Investigator and an improvement of 
severity from baseline of at least 2 levels of 
severity in the PR-PCSS of that same left 
buttock) (Days 22, 43, and 71) 
• Proportion of 2-level CR-PCSS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both the target and non-target 
buttocks 
• Proportion of 1-level CR-PCSS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both the target and non-target 
buttocks 
• Proportion of 1-level composite responders 
of the target buttock (defined as subjects 
with an improvement in severity from 
baseline of at least 1 level of severity in the 
CR-PCSS of the target buttock assessed 
live by the Investigator and an 
improvement of severity from baseline of 
at least 1 level of severity in the PR-PCSS 
of that same target buttock) (Days 22, 43, 
and 71) 
• Proportion of 1-level composite responders 
of the non-target buttock (defined as 
subjects with an improvement in severity 
from baseline of at least 1 level of severity 
in the CR-PCSS of the non-target buttock 
assessed live by the Investigator and an 
improvement of severity from baseline of 
at least 1 level of severity in the PR-PCSS 
of that same non-target buttock) (Days 22, 
43, and 71) 
• Proportion of 1-level composite responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the 
target buttock or non-target buttock or both 
buttocks in that subject. 
• Proportion of 1-level composite responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both the target and non-target 
buttocks. 

EN3835-303 Protocol Amendment 3 
05-Jun-2018 
Endo Pharmaceuticals Inc. 
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Section 
Original Text 
Revised Text 
• Proportion of 2-level composite responders 
of the right buttock (defined as subjects 
with an improvement in severity from 
baseline of at least 2 levels of severity in 
the CR-PCSS of the right buttock assessed 
live by the Investigator and an 
improvement of severity from baseline of 
at least 2 levels of severity in the PR-PCSS 
of that same right buttock) (Days 22, 43, 
and 71) 
• Proportion of 2-level composite responders 
of at least one of two buttocks (Days 22, 
43, and 71). A subject will be considered a 
responder if this criterion is met in the left 
buttock or right buttock or both buttocks in 
that subject. 
• Proportion of 2-level composite responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both left and right buttocks. 
• Proportion of subjects at each level of the 
S-GAIS of the left buttock (Days 22, 43, 
and 71) 
• Proportion of subjects at each level of the 
S-GAIS of the right buttock (Days 22, 43, 
and 71) 
• Proportion of 1-level S-GAIS responders 
defined as subjects with a response of at 
least 1 (improved) in the S- GAIS of the 
left buttock (Days 22, 43, and 71) 
• Proportion of 1-level S-GAIS responders 
defined as subjects with a response of at 
least 1 (improved) in the S- GAIS of the 
right buttock (Days 22, 43, and 71) 
• Proportion 1-level S-GAIS responders of at 
least one buttock (Days 22, 43, and 71). A 
subject will be considered a responder if 
this criterion is met in the left buttock or 
right buttock or both buttocks in that 
subject. 
• Proportion of 1-level S-GAIS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both left and right buttocks. 
• Proportion of subjects at each level of the 
I-GAIS of the left buttock (Days 22, 43, 
and 71) 
• Proportion of subjects at each level of the 
I-GAIS of the right buttock (Days 22, 43, 
and 71) 
• Proportion of 2-level composite responders 
of the target buttock (defined as subjects 
with an improvement in severity from 
baseline of at least 2 levels of severity in 
the CR-PCSS of the target buttock assessed 
live by the Investigator and an 
improvement of severity from baseline of 
at least 2 levels of severity in the PR-PCSS 
of that same target buttock) (Days 22, 43, 
and 71) 
• Proportion of 2-level composite responders 
of the non-target buttock (defined as 
subjects with an improvement in severity 
from baseline of at least 2 levels of severity 
in the CR-PCSS of the non-target buttock 
assessed live by the Investigator and an 
improvement of severity from baseline of 
at least 2 levels of severity in the PR-PCSS 
of that same non-target buttock) (Days 22, 
43, and 71)  
• Proportion of 2-level composite responders 
of at least one of two buttocks (Days 22, 
43, and 71). A subject will be considered a 
responder if this criterion is met in the 
target buttock or non-target buttock or both 
buttocks in that subject. 
• Proportion of 2-level composite responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both the target and non-target 
buttocks. 
• Proportion of subjects at each level of the 
S-GAIS of the target buttock (Days 22, 43, 
and 71) 
• Proportion of subjects at each level of the 
S-GAIS of the non-target buttock (Days 
22, 43, and 71) 
• Proportion of 1-level S-GAIS responders 
defined as subjects with a response of at 
least 1 (improved) in the S-GAIS of the 
target buttock (Days 22, 43, and 71) 
• Proportion of 1-level S-GAIS responders 
defined as subjects with a response of at 
least 1 (improved) in the S-GAIS of the 
non-target buttock (Days 22, 43, and 71) 
• Proportion 1-level S-GAIS responders of at 
least one buttock (Days 22, 43, and 71). A 
subject will be considered a responder if 
this criterion is met in the target buttock or 
non-target buttock or both buttocks in that 
subject. 

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05-Jun-2018 
Endo Pharmaceuticals Inc. 
Page 11 
 
 
 
Section 
Original Text 
Revised Text 
• Proportion of 1-level I-GAIS responders 
(defined as subjects with a response of at 
least 1 (improved) in the Investigator GAIS 
assessment) of at least one buttock (Days 
22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in the left buttock or right buttock or 
both buttocks in that subject. 
• Proportion of 1-level I-GAIS responders of 
two buttocks in the same individual (Days 
22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both left and right buttocks. 
• Change from baseline (Day 1) of the PR-
CIS total score at Day 71 
• Change from baseline (Day 1) of the 
abbreviated PR-CIS score at Day 71 
• Proportion of subjects with a change from 
baseline (Day1) of the PR-CIS ≥12 at 
Day 71 
• Proportion of subjects with a change from 
baseline (Day 1) of the abbreviated PR-CIS 
≥10 at Day 71 
• Proportion of subjects at each level of the 
subject satisfaction with cellulite treatment 
(Day 71) 
• Proportion of satisfied responders (defined 
as subjects with a response of at least 1 
(ie, 1 Satisfied or 2-Very Satisfied) in the 
subject satisfaction with cellulite treatment 
assessment (Day 71) 
• Proportion of 1-level S-GAIS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both the target and non-target 
buttocks. 
• Proportion of subjects at each level of the 
I-GAIS of the target buttock (Days 22, 43, 
and 71) 
• Proportion of subjects at each level of the 
I-GAIS of the non-target buttock (Days 22, 
43, and 71) 
• Proportion of 1-level I-GAIS responders 
defined as subjects with a response of at 
least 1 (improved) in the I-GAIS of the 
target buttock (Days 22, 43, and 71) 
• Proportion of 1-level I-GAIS responders 
defined as subjects with a response of at 
least 1 (improved) in the I-GAIS of the 
non-target buttock (Days 22, 43, and 71) 
• Proportion of 1-level I-GAIS responders of 
at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if 
this criterion is met in the target buttock or 
non-target buttock or both buttocks in that 
subject. 
• Proportion of 1-level I-GAIS responders of 
two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both the target and non-target 
buttocks. 
• Change from baseline (Day 1) of the 
PR-CIS score at Day 71 
• Change from baseline (Day 1) of the 
abbreviated PR-CIS score at Day 71 
• Proportion of subjects with a change from 
baseline (Day1) of the PR-CIS ≥12 at 
Day 71 
• Proportion of subjects with a change from 
baseline (Day 1) of the abbreviated PR-CIS 
≥10 at Day 71 
• Proportion of subjects at each level of the 
subject self-rating scale (SSRS) (Day 1 
(Baseline) and Day 71 
• Proportion of 1-level SSRS responders 
defined as subjects who were at least 
slightly satisfied at Day 71 (SSRS rating 
≥ 4) 
• Proportion of subjects at each level of the 
subject satisfaction with cellulite treatment 
assessment (Day 71) 

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• Proportion of satisfied responders (defined 
as subjects with a response of at least 1 
(ie, 1 Satisfied or 2-Very Satisfied) in the 
subject satisfaction with cellulite treatment 
assessment (Day 71) 
5 Schedule of 
Events 
Added table row 
• Subject Self-Rating Scale (SSRS) 
Day 1 Treatment Visit 1: Xc 
Day 71 (+ 5d)/End of Study/Early 
Termination: X 
7 List of 
Abbreviations, 
Table 2: 
Abbreviations 
and Special 
Terms 
Added table rows 
SSRS: Subject Self-Rating Scale 
MI: Multiple imputation 
11.2 Subject 
Exclusion 
Criteria 
13. Was a subject in a previous cellulite 
clinical trial of CCH: AUX-CC-830, 
AUX-CC-831, EN3835-102, 
EN3835-104, EN3835-201, and/or 
EN3835-202 
13. Was a subject in a previous cellulite 
clinical trial of CCH: AUX-CC-830, 
AUX-CC-831, EN3835-102, 
EN3835-104, EN3835-201, EN3835-202, 
and/or EN3835-205 
12.4.1 Treatment 
Visit 1: 
Pre-Injection 
Added text 
6. Subjects will complete the SSRS 
assessment (section 13.1.2.5); the 
Investigator is blinded to these ratings 
Added text 
9. Upon confirmation of two buttocks 
eligible for treatment (eligible criteria 
being each buttock have PR-PCSS and 
CR-PCSS scores of 3 or 4), the IWRS 
system will randomly assign one buttock 
as the target buttock in the background. 
Subjects, investigators, site personnel and 
Endo personnel will be blinded to target 
buttock assignment. 
8. Randomization of subjects with two 
buttocks eligible for treatment (eligible 
criteria being each buttock have PR-PCSS 
and CR-PCSS scores of 3 or 4) to 
treatment (section 12.10); obtain kit 
numbers of study treatment 
10. Randomization of subjects with two 
buttocks eligible for treatment (eligible 
criteria being each buttock have PR-PCSS 
and CR-PCSS scores of 3 or 4) to 
treatment (section 12.10); obtain kit 
numbers of study treatment. Subjects, 
investigators, site personnel, and Endo 
personnel will be blinded to treatment 
assignment. 
12.6 Day 71 
(+5 days) / End 
of Study / Early 
Termination 
6. Subject Cellulite Assessment of each of the 
two buttocks using the photographic image 
before marking dimples and injection sites 
(NOTE: complete subject cellulite 
assessments before Investigator cellulite 
assessments) using: 
6. Subject Cellulite Assessment of each of the 
two buttocks using the photographic image 
before marking dimples and injection sites 
(NOTE: complete subject cellulite 
assessments before Investigator cellulite 
assessments) using: 
 
a. Patient Reported Photonumeric Cellulite 
Severity Scale (PR-PCSS) assessment 
(section 13.1.2.1) 
a. Patient Reported Photonumeric Cellulite 
Severity Scale (PR-PCSS) assessment 
(section 13.1.2.1) 
 
b. Subject Global Aesthetic Improvement 
Scale (S-GAIS) (section 13.1.2.2) 
b. Subject Global Aesthetic Improvement 
Scale (S-GAIS) (section 13.1.2.2) 

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c. Patient Reported Cellulite Impact Scale 
(PR-CIS) assessment (section 13.1.2.3); 
note this assessment is of both left and 
right buttocks rather than each individual 
buttock 
c. Patient Reported Cellulite Impact Scale 
(PR-CIS assessment (section 13.1.2.3); 
note this assessment is of both left and 
right buttocks rather than each individual 
buttock 
 
d. Subject Satisfaction with Cellulite 
Treatment Assessment (section 13.1.2.4); 
note this assessment is of both left and 
right buttocks rather than each individual 
buttock 
d. Subject Satisfaction with Cellulite 
Treatment Assessment (section 13.1.2.4); 
note this assessment is of both left and 
right buttocks rather than each individual 
buttock 
 
 
e. Subject Self-Rating Scale assessment 
(section 13.1.2.5); note this assessment is 
of both left and right buttocks rather than 
each individual buttock 
12.10 Blinding 
and 
Randomization 
On Day 1, if each of the buttocks again meet 
the criteria (3 or 4 on the PR-PCSS and CR-
PCSS), the subject will be randomized to a 
treatment group. 
On Day 1, if each of the buttocks (ie, both 
buttocks) again meet the criteria (3 or 4 on 
the PR-PCSS and CR-PCSS), one buttock 
will be randomly assigned by the IWRS as 
the target buttock for the primary efficacy 
endpoint. Subjects, investigators, site 
personnel and Endo personnel will be blinded 
to the identification of the target buttock.  
On Day 1, if each of the buttocks (ie, both 
buttocks) again meet the criteria (3 or 4 on the 
PR-PCSS and CR-PCSS), the subject will be 
randomized to a treatment group.  
13.1.2.5 Subject 
Self-Rating Scale 
(SSRS) 
Added section 
13.1.2.5. Subject Self-Rating Scale (SSRS) 
The SSRS is a measure that assesses subject 
satisfaction with appearance in association 
with cellulite on the buttocks using whole 
numbers on a 7-level scale that ranges from 0 
(extremely dissatisfied) to 6 (extremely 
satisfied). The patient will be asked to respond 
to the question related to the satisfaction with 
appearance of the cellulite on their buttocks on 
the appropriate visit day (note Day 71 question 
is different than Day 1 question). No 
photographs or reference to previous ratings or 
evaluations will be used. Subjects will be 
given a list of responses and they will provide 
a rating from those below that best represents 
their answer (Table 7); the list of responses is 
the same for Day 1 and for Day 71. 
On Day 1 (Baseline), subjects will be 
instructed to answer: Considering your 
appearance in association with your cellulite 
on your buttocks, how satisfied do you feel 
with your appearance at the present time? 

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On Day 71, subjects will be instructed to 
answer: Considering your appearance in 
association with your cellulite on your 
buttocks, how satisfied do you feel with your 
appearance at the present time whether or not 
in your judgment it is due entirely to treatment 
with EN3835? 
This variable will be entered directly into the 
EDC system, thus the electronic database will 
serve as the direct point of data capture and 
will serve as source for this variable. 
Table 7: Subject Self-Rating Scale (SSRS) 
Rating 
Response Option 
6 
Extremely satisfied 
5 
Satisfied 
4 
Slightly satisfied 
3 
Neither satisfied nor dissatisfied 
2 
Slightly dissatisfied 
1 
Dissatisfied 
0 
Extremely dissatisfied 
 
14.6.1 Adverse 
Events of Special 
Interest 
Adverse events such as bruising, ecchymosis, 
hematomas, and contusions that occur remote 
to the site of drug administration, or any 
hypersensitivity reactions, including 
anaphylaxis, will be recorded as an AE or 
SAE as appropriate (see section 14.1.1, 
Adverse Events or section 14.1.2, Serious 
Adverse Events). 
Adverse events such as bruising, ecchymosis, 
hematomas, and contusions that occur remote 
to the site of drug administration, or any 
hypersensitivity reactions, including 
anaphylaxis, will be recorded and evaluated 
for seriousness and severity (see section 
14.1.1, Adverse Events or section 14.1.2, 
Serious Adverse Events). 
In addition, local AEs associated with the 
injection site, including bruising, pain, 
nodules/mass, ulceration, erythema, pruritus, 
swelling, and/or induration, will be recorded 
and evaluated for seriousness and severity (see 
as appropriate, section 14.1.1, Adverse Events 
or section 14.1.2, Serious Adverse Events) 
17.1 
Determination of 
Sample Size 
The primary variable is the proportion of 
2-level composite responders at Day 71 
defined as subjects with at least one of two 
treated buttocks with: 
• an improvement in severity from baseline 
(Day 1 visit) of at least 2 levels of severity 
in the CR-PCSS as assessed live by the 
Investigator, and 
• an improvement in severity from baseline 
of at least 2 levels of severity in the 
PR-PCSS as assessed by the subject while 
viewing the digital image of the same 
buttock. 
The primary variable is the proportion of 
2-leve composite responders at Day 71 
defined as subjects with: 
• an improvement in severity from baseline 
(Day 1 visit) of at least 2 levels of severity 
in the CR-PCSS as assessed live by the 
Investigator of the target buttock, and 
• an improvement in severity from baseline 
of at least 2 levels of severity in the 
PR-PCSS as assessed by the subject while 
viewing the digital image of the target 
buttock. 

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17.2.3 Modified 
Intent-to-Treat 
(mITT) 
Population 
The mITT population is defined as all intent-
to-treat subjects with a baseline and at least 1 
post-injection evaluation of both the 
Investigator CR-PCSS and subject PR-PCSS 
for both left and right buttocks.. 
The mITT population is defined as all intent-
to-treat subjects with a baseline and at least 1 
post-injection evaluation of both the 
Investigator CR-PCSS and subject PR-PCSS 
for both the target and non-target buttocks.  
17.2.4 Per-
Protocol (PP) 
Population 
The per-protocol population is defined as the 
mITT subjects without any major protocol 
deviation that will impact the subject’s 
efficacy and safety.  
The per-protocol population is defined as the 
mITT subjects without any of the following:  
• Placebo-assigned subject receives EN3835 
treatment 
• EN3835-assigned subject receives placebo 
treatment only throughout the study 
• Any subject receives protocol-prohibited 
medications 
• Subject lacking PR-PCSS and/or CR-PCSS 
assessment at Day 71 
• Any major protocol deviation that is 
deemed as impacting subject efficacy 
17.5 Efficacy 
Analysis 
Changes in the PR-PCSS ratings and 
CR-PCSS ratings from baselines, S-GAIS 
scores, and I-GAIS scores will be analyzed 
using the Wilcoxon rank sum test. 
Changes in the PR-PCSS ratings and 
CR-PCSS ratings from baselines, S-GAIS 
scores, I-GAIS scores, and SSRS scores will 
be analyzed using the Wilcoxon rank sum test. 
Changes in PR-CIS from baselines will be 
analyzed using an analysis of covariance 
(ANCOVA) adjusted for baseline values. 
Similarly family #2 key secondary efficacy 
analyses will be performed only if at least one 
of the key secondary efficacy endpoints of 
family #1 is significant (p ≤ 0.025; parallel 
gatekeeping strategy 
Similarly family #2 key secondary efficacy 
analyses will be performed only if at least one 
of the key secondary efficacy endpoints of 
family #1 is significant (p ≤ 0.0125; parallel 
gatekeeping strategy) and family #3 key 
secondary efficacy analyses will be performed 
only if at least one of the key secondary 
efficacy endpoints of family #2 is significant 
(parallel gatekeeping strategy). 
Changes in the PR-PCSS ratings and CR-
PCSS ratings from baselines, S-GAIS scores, 
and I-GAIS scores will be analyzed using the 
Wilcoxon rank sum test. 
Changes in the PR-PCSS ratings and 
CR-PCSS ratings from baselines, S-GAIS 
scores, I-GAIS scores, and SSRS scores will 
be analyzed using the Wilcoxon rank sum test. 
17.5.1 Primary 
Efficacy 
Variable 
The primary efficacy variable is the proportion 
of 2-level composite responders at Day 71 
defined as subjects with at least one of two 
treated buttocks with: 
• an improvement in severity from baseline 
(Day 1 visit) of at least 2 levels of severity 
in the CR-PCSS as assessed live by the 
Investigator, and 
• an improvement in severity from baseline 
of at least 2 levels of severity in the 
PR-PCSS by the subject while viewing the 
digital image of the same buttock. 
The primary efficacy variable is the proportion 
of 2-level composite responders at Day 71 
defined as subjects with: 
• an improvement in severity from baseline 
(Day 1 visit) of at least 2 levels of severity 
in the CR-PCSS as assessed live by the 
Investigator of the target buttock, and 
• an improvement in severity from baseline 
of at least 2 levels of severity in the 
PR-PCSS by the subject while viewing the 
digital image of the target buttock. 

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A subject will be considered a responder if 
these criteria are met in either the left buttock 
or right buttock or both buttocks in that 
subject. In other words, a subject will be 
considered a responder if she has an 
improvement of at least 2 levels on the 
PR-PCSS and an improvement of at least 
2 levels on the CR-PCSS on that same 
buttock; that buttock could be the left buttock 
or right buttock or both buttocks. 
A subject will be considered a responder if 
these criteria are met in the randomized target 
buttock of that subject. 
17.5.2.1 Key 
Secondary 
Variables 
There will be 4 key secondary endpoints 
grouped in two families of 2 endpoints per 
family analyzed in a hierarchical order. 
• Family #1 – two endpoints: 
− Proportion of 1-level PR-PCSS responders 
defined as subjects with ≥1-level 
improvement in PR-PCSS severity rating 
of left buttock at Day 71 compared to 
Day 1 
− Proportion of 1-level PR-PCSS responders 
defined as subjects with ≥1-level 
improvement in PR-PCSS severity rating 
of right buttock at Day 71 compared to 
Day 1 
• Family #2 – two endpoints: 
− Proportion of 1-level S-GAIS responders 
defined as subjects with ≥1-level 
improvement (improved, much improved 
or very much improved) in the S- GAIS 
assessment of left buttock at Day 71 
− Proportion of 1-level S-GAIS responders 
defined as subjects with ≥1-level 
improvement (improved, much improved 
or very much improved) in the S-GAIS 
assessment of right buttock at Day 71 
There will be 8 key secondary endpoints 
grouped in three families of 2-4 endpoints per 
family analyzed in hierarchical order. 
• Family #1 – four endpoints: 
− Proportion of 1-level PR-PCSS responders 
defined as subjects with ≥1-level 
improvement in PR-PCSS severity rating 
of target buttock at Day 71 compared to 
Day 1 
− Proportion of 2-level PR-PCSS responders 
defined as subjects with ≥2-level 
improvement in PR-PCSS severity rating 
of target buttock at Day 71 compared to 
Day 1 
− Proportion of 1-level composite responders 
of target buttock (defined as subjects with 
an improvement in severity from baseline 
of at least 1 level of severity in the CR-
PCSS of the target buttock assessed live by 
the Investigator and an improvement of 
severity from baseline of at least 1 level of 
severity in the PR-PCSS of the target 
buttock) at Day 71 compared to Day 1 
− Proportion of 2-level composite responders 
of non-target buttock at Day 71 compared 
to Day 1 
• Family #2 – two endpoints: 
− Proportion of 1-level SSRS responders 
defined as subjects who were at least 
slightly satisfied at Day 71 (SSRS rating 
≥ 4)  
− Proportion of subjects with a change from 
baseline (Day1) of the PR-CIS ≥12 at 
Day 71 
• Family #3 – two endpoints: 
− Proportion of 1-level S-GAIS responders 
defined as subjects with ≥1-level 
improvement (improved, much improved 
or very much improved) in the S-GAIS 
assessment of the target buttock at Day 71 

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− Proportion of 2-level S-GAIS responders 
defined as subjects with ≥2-level 
improvement (much improved or very 
much improved) in the S-GAIS assessment 
of the target buttock at Day 71 
Added text 
Sensitivity analyses for the key secondary 
endpoints will include: 
• ITT subjects with missing data handled by 
multiple imputation (MI) approach 
• ITT subjects with missing data handled by 
an LOCF approach 
• mITT subjects with missing data handled 
by an LOCF approach 
• Observed data only (no missing data 
handling) 
• Per-protocol (PP) subjects with missing 
data handled by an LOCF approach if 10% 
or more subjects are excluded in the PP 
population from mITT population 
17.5.3.1 
Supportive 
Variables 
• 
Proportion of 2-level PR-PCSS responders 
defined as subjects with an improvement 
in severity from baseline of at least 2 
levels of severity in the PR-PCSS of the 
left buttock (Days 22, 43, and 71) 
• 
Proportion of 2-level PR-PCSS responders 
defined as subjects with an improvement 
in severity from baseline of at least 2 
levels of severity in the PR-PCSS of the 
right buttock (Days 22, 43, and 71) 
• 
Proportion of 1-level PR-PCSS responders 
defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the PR-PCSS of left buttock 
(Days 22, 43, and 71) 
• 
Proportion of 1-level PR-PCSS responders 
defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the PR-PCSS of right 
buttock (Days 22, 43, and 71) 
• 
Proportion of 2-level PR-PCSS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the left 
buttock or right buttock or both buttocks 
in that subject. 
• 
Proportion of 1-level PR-PCSS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the left 
buttock or right buttock or both buttocks 
in that subject. 
• 
Proportion of 2-level PR-PCSS responders 
defined as subjects with an improvement 
in severity from baseline of at least 2 
levels of severity in the PR-PCSS of the 
target buttock (Days 22, 43, and 71) 
• 
Proportion of 2-level PR-PCSS responders 
defined as subjects with an improvement 
in severity from baseline of at least 2 
levels of severity in the PR-PCSS of the 
non-target buttock (Days 22, 43, and 71) 
• 
Proportion of 1-level PR-PCSS responders 
defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the PR-PCSS of the target 
buttock (Days 22, 43, and 71) 
• 
Proportion of 1-level PR-PCSS responders 
defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the PR-PCSS of the non-
target buttock (Days 22, 43, and 71) 
• 
Proportion of 2-level PR-PCSS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the 
target buttock or non-target buttock or 
both buttocks in that subject. 
• 
Proportion of 1-level PR-PCSS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the 
target buttock or non-target buttock or 
both buttocks in that subject. 

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• 
Proportion of 2-level PR-PCSS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both left and right buttocks. 
• 
Proportion of 1-level PR-PCSS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both left and right buttocks. 
• 
Proportion of 2-level CR-PCSS 
responders defined as subjects with an 
improvement in severity from baseline of 
at least 2 levels of severity in the 
CR-PCSS of the left buttock (Days 22, 43, 
and 71) 
• 
Proportion of 2-level CR-PCSS 
responders defined as subjects with an 
improvement in severity from baseline of 
at least 2 levels of severity in the 
CR-PCSS of the right buttock (Days 22, 
43, and 71) 
• 
Proportion of 1-level CR-PCSS 
responders defined as subjects with an 
improvement in severity from baseline of 
at least 1 level of severity in the CR-PCSS 
of the left buttock (Days 22, 43, and 71) 
• 
Proportion of 1-level CR-PCSS 
responders defined as subjects with an 
improvement in severity from baseline of 
at least 1 level of severity in the CR-PCSS 
of the right buttock (Days 22, 43, and 71) 
• 
Proportion of 2-level CR-PCSS 
responders of at least one buttock 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in the left buttock or right buttock or 
both buttocks in that subject. 
• 
Proportion of 1-level CR-PCSS 
responders of at least one buttock 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in the left buttock or right buttock or 
both buttocks in that subject. 
• 
Proportion of 2-level CR-PCSS 
responders of two buttocks in the same 
individual (Days 22, 43, and 71). A 
subject will be considered a responder if 
this criterion is met in both left and right 
buttocks. 
• 
Proportion of 2-level PR-PCSS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both the target and non-target 
buttocks. 
• 
Proportion of 1-level PR-PCSS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both the target and non-target 
buttocks. 
• 
Proportion of 2-level CR-PCSS 
responders defined as subjects with an 
improvement in severity from baseline of 
at least 2 levels of severity in the 
CR-PCSS of the target buttock (Days 22, 
43, and 71) 
• 
Proportion of 2-level CR-PCSS 
responders defined as subjects with an 
improvement in severity from baseline of 
at least 2 levels of severity in the 
CR-PCSS of the non-target buttock (Days 
22, 43, and 71) 
• 
Proportion of 1-level CR-PCSS 
responders defined as subjects with an 
improvement in severity from baseline of 
at least 1 level of severity in the CR-PCSS 
of the target buttock (Days 22, 43, and 71) 
• 
Proportion of 1-level CR-PCSS 
responders defined as subjects with an 
improvement in severity from baseline of 
at least 1 level of severity in the CR-PCSS 
of the non-target buttock (Days 22, 43, 
and 71) 
• 
Proportion of 2-level CR-PCSS 
responders of at least one buttock 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in the target buttock or non-target 
buttock or both buttocks in that subject. 
• 
Proportion of 1-level CR-PCSS 
responders of at least one buttock 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in the target buttock or non-target 
buttock or both buttocks in that subject. 
• 
Proportion of 2-level CR-PCSS 
responders of two buttocks in the same 
individual (Days 22, 43, and 71). A 
subject will be considered a responder if 
this criterion is met in both the target and 
non-target buttocks. 

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• 
Proportion of 1-level CR-PCSS 
responders of two buttocks in the same 
individual (Days 22, 43, and 71). A 
subject will be considered a responder if 
this criterion is met in both left and right 
buttocks. 
• 
Proportion of 1-level composite 
responders of the left buttock (defined as 
subjects with an improvement in severity 
from baseline of at least 1 level of severity 
in the CR-PCSS of the left buttock 
assessed live by the Investigator and an 
improvement of severity from baseline of 
at least 1 level of severity in the PR-PCSS 
of that same left buttock) (Days 22, 43, 
and 71) 
• 
Proportion of 1-level composite 
responders of the right buttock (defined as 
subjects with an improvement in severity 
from baseline of at least 1 level of severity 
in the CR-PCSS of the right buttock 
assessed live by the Investigator and an 
improvement of severity from baseline of 
at least 1 level of severity in the PR-PCSS 
of that same right buttock) (Days 22, 43, 
and 71) 
• 
Proportion of 1-level composite 
responders of at least one buttock 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in the left buttock or right buttock or 
both buttocks in that subject. 
• 
Proportion of 1-level composite 
responders of two buttocks in the same 
individual (Days 22, 43, and 71). A 
subject will be considered a responder if 
this criterion is met in both left and right 
buttocks. 
• 
Proportion of 2-level composite 
responders of the left buttock (defined as 
subjects with an improvement in severity 
from baseline of at least 2 levels of 
severity in the CR-PCSS of the left 
buttock assessed live by the Investigator 
and an improvement of severity from 
baseline of at least 2 levels of severity in 
the PR-PCSS of that same left buttock) 
(Days 22, 43, and 71)  
• 
Proportion of 1-level CR-PCSS 
responders of two buttocks in the same 
individual (Days 22, 43, and 71). A 
subject will be considered a responder if 
this criterion is met in both the target and 
non-target buttocks. 
• 
Proportion of 1-level composite 
responders of the target buttock (defined 
as subjects with an improvement in 
severity from baseline of at least 1 level of 
severity in the CR-PCSS of the target 
buttock assessed live by the Investigator 
and an improvement of severity from 
baseline of at least 1 level of severity in 
the PR-PCSS of that same target buttock) 
(Days 22, 43, and 71) 
• 
Proportion of 1-level composite 
responders of the non-target buttock 
(defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the CR-PCSS of the 
non-target buttock assessed live by the 
Investigator and an improvement of 
severity from baseline of at least 1 level of 
severity in the PR-PCSS of that same 
non-target buttock) (Days 22, 43, and 71) 
• 
Proportion of 1-level composite 
responders of at least one buttock 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in the target buttock or non-target 
buttock or both buttocks in that subject. 
• 
Proportion of 1-level composite 
responders of two buttocks in the same 
individual (Days 22, 43, and 71). A 
subject will be considered a responder if 
this criterion is met in both the target and 
non-target buttocks. 
• 
Proportion of 2-level composite 
responders of the target buttock (defined 
as subjects with an improvement in 
severity from baseline of at least 2 levels 
of severity in the CR-PCSS of the target 
buttock assessed live by the Investigator 
and an improvement of severity from 
baseline of at least 2 levels of severity in 
the PR-PCSS of that same target buttock) 
(Days 22, 43, and 71) 

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• 
Proportion of 2-level composite 
responders of the right buttock (defined as 
subjects with an improvement in severity 
from baseline of at least 2 levels of 
severity in the CR-PCSS of the right 
buttock assessed live by the Investigator 
and an improvement of severity from 
baseline of at least 2 levels of severity in 
the PR-PCSS of that same right buttock) 
(Days 22, 43, and 71) 
• 
Proportion of 2-level composite 
responders of at least one of two buttocks 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in the left buttock or right buttock or 
both buttocks in that subject.  
• 
Proportion of 2-level composite 
responders of two buttocks in the same 
individual (Days 22, 43, and 71). A 
subject will be considered a responder if 
this criterion is met in both left and right 
buttocks. 
• 
Proportion of subjects at each level of the 
S-GAIS of the left buttock (Days 22, 43, 
and 71) 
• 
Proportion of subjects at each level of the 
S-GAIS of the right buttock (Days 22, 43, 
and 71) 
• 
Proportion of 1-level S-GAIS responders 
defined as subjects with a response of at 
least 1 (improved) in the S- GAIS of the 
left buttock (Days 22, 43, and 71) 
• 
Proportion of 1-level S-GAIS responders 
defined as subjects with a response of at 
least 1 (improved) in the S- GAIS of the 
right buttock (Days 22, 43, and 71) 
• 
Proportion 1-level S-GAIS responders of 
at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if 
this criterion is met in the left buttock or 
right buttock or both buttocks in that 
subject. 
• 
Proportion of 1-level S-GAIS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both left and right buttocks. 
• 
Proportion of subjects at each level of the 
I-GAIS of the left buttock (Days 22, 43, 
and 71)  
• 
Proportion of 2-level composite 
responders of the non-target buttock 
(defined as subjects with an improvement 
in severity from baseline of at least 2 
levels of severity in the CR-PCSS of the 
non-target buttock assessed live by the 
Investigator and an improvement of 
severity from baseline of at least 2 levels 
of severity in the PR-PCSS of that same 
non-target buttock) (Days 22, 43, and 71) 
• 
Proportion of 2-level composite 
responders of at least one of two buttocks 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in the target buttock or non-target 
buttock or both buttocks in that subject.  
• 
Proportion of 2-level composite 
responders of two buttocks in the same 
individual (Days 22, 43, and 71). A 
subject will be considered a responder if 
this criterion is met in both the target and 
non-target buttocks. 
• 
Proportion of subjects at each level of the 
S-GAIS of the target buttock (Days 22, 
43, and 71) 
• 
Proportion of subjects at each level of the 
S-GAIS of the non-target buttock 
(Days 22, 43, and 71) 
• 
Proportion of 1-level S-GAIS responders 
defined as subjects with a response of at 
least 1 (improved) in the S-GAIS of the 
target buttock (Days 22, 43, and 71) 
• 
Proportion of 1-level S-GAIS responders 
defined as subjects with a response of at 
least 1 (improved) in the S-GAIS of the 
non-target buttock (Days 22, 43, and 71) 
• 
Proportion 1-level S-GAIS responders of 
at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if 
this criterion is met in the target buttock or 
non-target buttock or both buttocks in that 
subject. 
• 
Proportion of 1-level S-GAIS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both the target and non-target right 
buttocks. 
• 
Proportion of subjects at each level of the 
I-GAIS of the target buttock (Days 22, 43, 
and 71)  

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• 
Proportion of subjects at each level of the 
I-GAIS of the right buttock (Days 22, 43, 
and 71) 
• 
Proportion of 1-level I-GAIS responders 
(defined as subjects with a response of at 
least 1 (improved) in the Investigator 
GAIS assessment) of at least one buttock 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in the left buttock or right buttock or 
both buttocks in that subject.  
• 
Proportion of 1-level I-GAIS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both left and right buttocks. 
• 
Change from baseline (Day 1) of the 
PR-CIS total score at Day 71 
• 
Change from baseline (Day 1) of the 
abbreviated PR-CIS score at Day 71 
• 
Proportion of subjects with a change from 
baseline (Day 1) of the PR-CIS ≥ 12 at 
Day 71 
• 
Proportion of subjects with a change from 
baseline (Day 1) of the abbreviated 
PR-CIS ≥ 10 at Day 71 
• 
Proportion of subjects at each level of the 
subject satisfaction with cellulite 
treatment (Day 71) 
• 
Proportion of satisfied responders (defined 
as subjects with a response of at least 1 
(ie, 1 Satisfied or 2 Very Satisfied) in the 
subject satisfaction with cellulite 
treatment assessment (Day 71) 
• 
Proportion of subjects at each level of the 
I-GAIS of the non-target buttock 
(Days 22, 43, and 71) 
• 
Proportion of 1-level I-GAIS responders 
defined as subjects with a response of at 
least 1 (improved) in the I-GAIS of the 
target buttock (Days 22, 43, and 71) 
• 
Proportion of 1-level I-GAIS responders 
defined as subjects with a response of at 
least 1 (improved) in the I-GAIS of the 
non-target buttock (Days 22, 43, and 71) 
• 
Proportion of 1-level I-GAIS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the 
target buttock or non-target buttock or 
both buttocks in that subject.  
• 
Proportion of 1-level I-GAIS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both the target and non-target 
buttocks. 
• 
Change from baseline (Day 1) of the 
PR-CIS total score at Day 71 
• 
Change from baseline (Day 1) of the 
abbreviated PR-CIS score at Day 71 
• 
Proportion of subjects with a change from 
baseline (Day 1) of the PR-CIS ≥ 12 at 
Day 71 
• 
Proportion of subjects with a change from 
baseline (Day 1) of the abbreviated 
PR-CIS ≥ 10 at Day 71 
• 
Proportion of subjects at each level of the 
SSRS (Day 1 (Baseline) and Day 71) 
• 
Proportion of 1-level SSRS responders 
defined as subjects who were at least 
slightly satisfied at Day 71 (SSRS rating 
≥ 4) 
• 
Proportion of subjects at each level of the 
subject satisfaction with cellulite treatment 
assessment (Day 71) 
• 
Proportion of satisfied responders (defined 
as subjects with a response of at least 1 
(ie, 1 Satisfied or 2 Very Satisfied) in the 
subject satisfaction with cellulite treatment 
assessment (Day 71) 

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4 Synopsis, 
Study Design 
Subjects with 2 treatment areas (bilateral 
buttocks) (also referred to as quadrants) with 
moderate or severe levels of cellulite as 
independently assessed by the subject using 
the Patient Reported Photonumeric Cellulite 
Severity Scale (PR-PCSS) and by the 
Investigator using the Clinician Reported 
Photonumeric Cellulite Severity Scale 
(CR-PCSS) and a Hexsel Cellulite Severity 
Scale no greater than 13 will be eligible. 
Subjects with 2 treatment areas (bilateral 
buttocks) (also referred to as quadrants) with 
moderate or severe levels of cellulite as 
independently assessed by the subject using 
the Patient Reported Photonumeric Cellulite 
Severity Scale (PR-PCSS) and by the 
Investigator using the Clinician Reported 
Photonumeric Cellulite Severity Scale 
(CR-PCSS) will be eligible. 
Add text 
At Day 1, the subject will complete a Patient 
Reported Cellulite Impact Scale (PR-CIS) 
assessment. 
4 Synopsis, 
Diagnosis and 
Inclusion/ 
Exclusion 
Criteria, 
Inclusion 
Criteria 
3. At Screening visit, have 2 bilateral 
buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as 
reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as 
reported by the Investigator (CR-PCSS), 
and 
c. a Hexsel CSS score no greater than 13 
3. At Screening visit, have 2 bilateral 
buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as 
reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as 
reported by the Investigator (CR-PCSS) 
4. At Day 1 visit, have 2 bilateral buttocks 
with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as 
reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as 
reported by the Investigator (CR-PCSS), 
and 
c. a Hexsel CSS score no greater than 13 
4. At Day 1visit, have 2 bilateral buttocks 
with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as 
reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as 
reported by the Investigator (CR-PCSS) 
4 Synopsis, 
Diagnosis and 
Inclusion/ 
Exclusion 
Criteria, 
Exclusion 
Criteria  
2. Has any of the following local conditions 
in the areas to be treated: 
a. History of lower extremity thrombosis or 
post-thrombosis syndrome 
b. Vascular disorder (eg, varicose veins, 
telangiectasia) in area to be treated 
c. Inflammation or active infection 
d. Active cutaneous alteration including rash, 
eczema, psoriasis, or skin cancer 
e. Has a tattoo and/or a mole located within 
2 cm of the site of injection  
2. Has any of the following local conditions 
in the areas to be treated: 
a. History of lower extremity thrombosis or 
post-thrombosis syndrome 
b. Vascular disorder (eg, varicose veins, 
telangiectasia) in area to be treated 
c. Inflammation or active infection 
d. Severe skin laxity, flaccidity, and/or 
sagging  
e. Active cutaneous alteration including rash, 
eczema, psoriasis, or skin cancer 
f. Has a tattoo and/or a mole located within 
2 cm of the site of injection 
4 Synopsis, 
Criteria for 
Evaluation, 
Efficacy 
Added text 
• Patient Reported Cellulite Impact Scale: 6 
questions with responses to each question 
consisting of a numerical rating scale 
(NRS) ranging from 0 (Not at all) to 10 
(Extremely) 

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4 Synopsis, 
Statistical 
Methods, 
Analysis, 
Supportive 
Endpoints 
Added text 
• Change from baseline (Day 1) of the 
PR-CIS total score at Day 71 
• Change from baseline (Day 1) of the 
abbreviated PR-CIS score at Day 71 
• Proportion of subjects with a change from 
baseline (Day1) of the PR-CIS ≥12 at 
Day 71 
• Proportion of subjects with a change from 
baseline (Day 1) of the abbreviated 
PR-CIS ≥10 at Day 71 
5 Schedule of 
Events, Physical 
examination 
Day -14 to -1 Screening: X 
Day 71 (+ 5d)/End of Study/Early 
Termination: X 
Day -14 to -1 Screening: X 
5 Schedule of 
Events, Subject 
cellulite 
assessments, 
Patient Reported 
Cellulite Impact 
Scale (PR-CIS) 
Added table row 
• Patient Reported Cellulite Impact Scale 
(PR-CIS) 
Day 1 Treatment Visit 1: Xc,g 
Day 71 (+ 5d)/End of Study/Early 
Termination: Xg 
5 Schedule of 
Events, 
Investigator 
cellulite 
assessments, 
Hexsel Cellulite 
Severity Scale 
(CSS) 
• Hexsel Cellulite Severity Scale (CSS) 
Day -14 to -1 Screening: Xb,i 
Day 1 Treatment Visit 1: Xc,b,i 
Deleted table row 
5 Schedule of 
Events, Table 
footnotes 
i Initial Hexsel CSS at Screening must be ≤13 
on each of 2 bilateral buttocks and the 
buttocks must again be ≤13 at Day 1 visit  
Deleted text 
j Before randomization, each of the subject’s 
buttocks must have ratings of 3 or 4 
(moderate or severe) in both the CR-PCSS 
and PR-PCSS, and Hexsel CSS score ≤13. 
i Before randomization, each of the subject’s 
buttocks must have ratings of 3 or 4 
(moderate or severe) in both the CR-PCSS 
and PR-PCSS. 
7. List of 
Abbreviations, 
Table 2: 
Abbreviations 
and Special 
Terms 
CSS: Cellulite severity scale 
Deleted table row 
Added table row 
PR-CIS: Patient Reported Cellulite Impact 
Scale 
11.1 Subject 
Inclusion 
Criteria 
3. At Screening visit, have 2 bilateral 
buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as 
reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as 
reported by the Investigator (CR-PCSS), 
and 
c. a Hexsel CSS score no greater than 13 
3. At Screening visit, have 2 bilateral 
buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as 
reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as 
reported by the Investigator (CR-PCSS) 

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4. At Day 1 visit, have 2 bilateral buttocks 
with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as 
reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as 
reported by the Investigator (CR-PCSS), 
and 
c. a Hexsel CSS score no greater than 13 
4. At Day 1 visit, have 2 bilateral buttocks 
with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as 
reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as 
reported by the Investigator (CR-PCSS)  
11.2 Subject 
Exclusion 
Criteria 
2. Has any of the following local conditions 
in the areas to be treated: 
a. History of lower extremity thrombosis or 
post-thrombosis syndrome 
b. Vascular disorder (eg, varicose veins, 
telangiectasia) in area to be treated 
c. Inflammation or active infection 
d. Active cutaneous alteration including rash, 
eczema, psoriasis, or skin cancer 
e. Has a tattoo and/or a mole located within 
2 cm of the site of injection 
2. Has any of the following local conditions 
in the areas to be treated: 
a. History of lower extremity thrombosis or 
post-thrombosis syndrome 
b. Vascular disorder (eg, varicose veins, 
telangiectasia) in area to be treated 
c. Inflammation or active infection 
d. Severe skin laxity, flaccidity, and/or 
sagging 
e. Active cutaneous alteration including rash, 
eczema, psoriasis, or skin cancer 
f. Has a tattoo and/or a mole located within 
2 cm of the site of injection 
12.1.2.2 
Screening Period 
(Day -14 to 
Day -1) 
5. Prior to Investigator CR-PCSS or Hexsel 
CSS assessment, subjects will rate each of 
their two buttocks using the PR-PCSS 
while viewing their digital images 
(section 13.1.2.1); the Investigator is 
blinded to these scores 
5. Prior to Investigator CR-PCSS assessment, 
subjects will rate each of their two 
buttocks using the PR-PCSS while viewing 
their digital images (section 13.1.2.1); the 
Investigator is blinded to these ratings 
6. After the subject has completed the 
PR-PCSS ratings, the Investigator will 
conduct live assessments of subject’s 
cellulite severity of each of the two 
buttocks using the CR-PCSS 
(section 13.1.2.4); the subject is blinded to 
these ratings 
7. After the Investigator has completed the 
CR-PCSS ratings, the Investigator will 
conduct live evaluation of each of the two 
buttocks using the Hexsel CSS; the subject 
is blinded to these ratings. The ratings 
from the PR-PCSS, CR-PCSS, and Hexsel 
CSS (section 13.1.2.6) will be used to 
assess initial eligibility of the buttocks for 
study entry 
6. After the subject has completed the 
PR-PCSS ratings, the Investigator will 
conduct live assessments of subject’s 
cellulite severity of each of the two 
buttocks using the CR-PCSS 
(section 13.1.2.5); the subject is blinded to 
these ratings. The ratings from the 
PR-PCSS and CR-PCSS will be used to 
assess initial eligibility of the buttocks for 
study entry 
12.2 Selecting 
and Marking 
Dimples during 
Treatment Visits 
The cellulite severity assessments using the 
PR-PCSS, CR-PCSS, and Hexsel CSS (note 
that the Hexsel CSS assessment is performed 
at Screening visit and Day 1 visit only) will be 
completed prior to marking dimples and 
injection sites. 
The cellulite severity assessments using the 
PR-PCSS and CR-PCSS, will be completed 
prior to marking dimples and injection sites. 

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12.4.1 Treatment 
Visit 1: Pre-
Injection 
4. Subjects will rate each of their buttocks 
using the PR-PCSS (section 13.1.2.1); the 
Investigator is blinded to these scores 
4. Subjects will rate each of their buttocks 
using the PR-PCSS (section 13.1.2.1); the 
Investigator is blinded to these ratings 
Added text 
5. Subjects will complete the Patient 
Reported Cellulite Impact Scale 
assessment (PR-CIS; section 13.1.2.3): the 
Investigator is blinded to this rating 
5. The Investigator will conduct live 
assessments of subject’s cellulite severity 
of each of the buttocks using the CR-PCSS 
(section 13.1.2.4); the subject is blinded to 
these ratings 
6. The Investigator will conduct live cellulite 
evaluation of each of the buttocks using 
the Hexsel CSS. The ratings from the 
PR-PCSS, CR-PCSS and Hexsel CSS 
(section 13.1.2.6) will be used to assess 
eligibility for randomization 
6. The Investigator will conduct live 
assessments of subject’s cellulite severity 
of each of the buttocks using the CR-PCSS 
(section 13.1.2.5); the subject is blinded to 
these ratings. The ratings from the 
PR-PCSS and CR-PCSS will be used to 
assess eligibility for randomization 
7. Subjects with PR-PCSS or CR-PCSS 
ratings in either of the buttocks <3 or a 
Hexsel CSS total score in either of the 
buttocks greater than 13 (section 13.1.2.6) 
will be excluded from participation 
7. Subjects with PR-PCSS or CR-PCSS 
ratings in either of the buttocks <3 will be 
excluded from participation 
8. Randomization of subjects with two 
buttocks eligible for treatment (eligible 
criteria being each buttock have PR-PCSS 
and CR-PCSS scores of 3 or 4 and a 
Hexsel CSS total score not greater than 13) 
to treatment (section 12.10); obtain kit 
numbers of study treatment 
8. Randomization of subjects with two 
buttocks eligible for treatment (eligible 
criteria being each buttock have PR-PCSS 
and CR-PCSS scores of 3 or 4) to 
treatment (section 12.10); obtain kit 
numbers of study treatment 
12.6 Day 71 
(+5 days)/End of 
Study/Early 
Termination 
6. Subject Cellulite Assessment of each of 
the two buttocks using the photographic 
image before marking dimples and 
injection sites (NOTE: complete subject 
cellulite assessments before Investigator 
cellulite assessments) using: 
a. Patient Reported Photonumeric Cellulite 
Severity Scale (PR-PCSS) assessment 
(section 13.1.2.1) 
b. Subject Global Aesthetic Improvement 
Scale (S-GAIS) (section 13.1.2.2) 
c. Subject Satisfaction with Cellulite 
Treatment Assessment (section 13.1.2.3); 
note this assessment is of both left and 
right buttocks rather than each individual 
buttock 
6. Subject Cellulite Assessment of each of the 
two buttocks using the photographic image 
before marking dimples and injection sites 
(NOTE: complete subject cellulite 
assessments before Investigator cellulite 
assessments) using: 
a. Patient Reported Photonumeric Cellulite 
Severity Scale (PR-PCSS) assessment 
(section 13.1.2.1) 
b. Subject Global Aesthetic Improvement 
Scale (S-GAIS) (section 13.1.2.2) 
c. Patient Reported Cellulite Impact Scale 
(PR-CIS assessment (section 13.1.2.3); 
note this assessment is of both left and 
right buttocks rather than each individual 
buttock 
d. Subject Satisfaction with Cellulite 
Treatment Assessment (section 13.1.2.4); 
note this assessment is of both left and 
right buttocks rather than each individual 
buttock 

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12.10 Blinding 
and Random-
ization 
On Day 1, if each of the buttocks again meet 
the criteria (3 or 4 on the PR-PCSS and 
CR-PCSS and no greater than 13 on Hexsel 
CSS) the subject will be randomized to a 
treatment group. 
On Day 1, if each of the buttocks again meet 
the criteria (3 or 4 on the PR-PCSS and 
CR-PCSS) the subject will be randomized to a 
treatment group. 
13.1.2.3 Patient 
Reported 
Cellulite Impact 
Scale (PR-CIS) 
Added section 
13.1.2.3. Patient Reported Cellulite Impact 
Scale (PR-CIS) 
At the Day 1 visit and Day 71 visit, subjects 
will be instructed to answer 6 questions 
related to the areas selected for treatment on 
their buttocks on the Patient Reported 
Cellulite Impact Scale (Appendix D) while 
viewing digital images of their buttocks. The 
PR-CIS assesses the visual and emotional 
impact of cellulite (happy, bothered, 
self-conscious, embarrassed, looking older or 
looking overweight or out of shape) using a 
6-question survey, with each question rated on 
a numerical rating scale from 0 (not at all) to 
10 (extremely). 
This variable will be entered directly into the 
EDC system, thus the electronic database will 
serve as the direct point of data capture and 
will serve as source for this variable. 
13.1.2.4 Subject 
Satisfaction  
Added text 
This variable will be entered directly into the 
EDC system, thus the electronic database will 
serve as the direct point of data capture and 
will serve as source for this variable. 
13.1.2.6 Hexsel 
Cellulite 
Severity Scale 
13.1.2.6. Hexsel Cellulite Severity Scale 
The Hexsel Cellulite Severity Scale (referred 
to as the Hexsel CSS) is a photonumeric scale 
that looks at 5 key morphologic features of 
cellulite: (A) number of evident depressions, 
(B) depth of depressions, (C) morphological 
appearance of skin surface alterations, (D) 
laxity, flaccidity or sagging of skin, and (E) 
current classification scale based on medical 
literature including Nürnberger and 
Müller.(12,13) Each of these features is 
evaluated on a 4-point scale from a low of 0 to 
a high of 3 as described in Table 8. The total 
score is the summation of all 5 features 
(Appendix D). 
Deleted section and table 

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The Investigator or qualified designee will 
independently use the Hexsel CSS to assess 
the severity of EFP in each of the two buttocks 
at the Screening visit and each of the two 
buttocks on Day 1 (Note: In this study, the 
Hexsel CSS is used exclusively for assessment 
of subject eligibility; it is not used as an 
efficacy assessment). All cellulite assessments 
should be made while the subject is in the 
standing position with relaxed gluteus 
muscles. However, when evaluating the 
subject for Category E (classification scale by 
Nürnberger and Müller) (13) if the subject has 
no evident depressions, the subject should be 
asked to contract her gluteus muscles or the 
pinch test should be applied (by pinching the 
skin between the thumb and index finger) so 
the Investigator or qualified designee can 
differentiate between scores/grades of zero (0) 
or I. 
This variable will be entered directly into the 
EDC system, thus the electronic database will 
serve as the direct point of data capture and 
will serve as source for this variable. 
[Table] 
 
17.5 Efficacy 
Analyses 
All supportive endpoints will be summarized 
as percentages. 
All supportive endpoints will be summarized 
as subject counts and percentages for 
categorical data or n, mean, SD, median, 
minimum, and maximum for continuous data. 
Added text 
Changes in PR-CIS from baselines will be 
analyzed using an analysis of covariance 
(ANCOVA) adjusted for baseline values 
17.5.3.1 
Supportive 
Variables 
Added text 
• Change from baseline (Day 1) of PR-CIS 
total score at Day 71 
• Change from baseline (Day 1) of 
abbreviated PR-CIS score at Day 71 
• Proportion of subjects with a change from 
baseline (Day 1) of PR-CIS ≥ 12 at Day 71 
• Proportion of subjects with a change from 
baseline (Day 1) of abbreviated PR-CIS 
≥ 10 at Day 71 
19.1 Source 
Documents 
This study allows for direct data entry (DDE) 
for selected data points as outlined below: 
• PR-PCSS 
• CR-PCSS 
• Hexsel CSS 
• S-GAIS 
• I-GAIS 
• Subject Satisfaction with Cellulite 
Treatment Assessment 
This study allows for direct data entry (DDE) 
for selected data points as outlined below: 
• PR-PCSS 
• CR-PCSS 
• S-GAIS 
• I-GAIS 
• PR-CIS 
• Subject Satisfaction with Cellulite 
Treatment Assessment 

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27 References 
12. Hexsel DM, Dal’Forno T, Hexsel CL. A 
validated photonumeric cellulite severity 
scale. J Eur Acad Dermatol Venereol. 
2009;23(5):523-8. 
13. Nürnberger F, Müller G. So-called 
cellulite: an invented disease. J Dermatol 
Surg Oncol. 1978;4(3):221-9. 
Deleted text 
APPENDIX D 
APPENDIX D. HEXSEL DM, DAL’FORNO 
T, HEXSEL CL. A VALIDATED 
PHOTONUMERIC CELLULITE SEVERITY 
SCALE. J EUR ACAD DERMATOL 
VENEREOL. 2009;23(5):523-8 
[Article] 
APPENDIX D. PATIENT REPORTED 
CELLULITE IMPACT SCALE (PR-CIS) 
Please select the rating that best represents 
your answer on a scale of 0 to 10 with 0 
representing “Not at all” and 10 representing 
“Extremely” while viewing digital images of 
your buttocks. Please answer each question. 
1. Thinking about the areas selected for 
treatment, how happy are you with the 
appearance of your cellulite? 
[Scale] 
2. Thinking about the areas selected for 
treatment, how bothered are you by the 
appearance of your cellulite? 
[Scale] 
3. Thinking about the areas selected for 
treatment, how self-conscious are you 
about the appearance of your cellulite? 
[Scale] 
4. Thinking about the areas selected for 
treatment, how embarrassed are you about 
the appearance of your cellulite? 
[Scale] 
5. Thinking about the areas selected for 
treatment, how much older do you look 
because of your cellulite? 
[Scale] 
6. Thinking about the areas selected for 
treatment, how overweight or out of shape 
do you look because of your cellulite? 
[Scale] 
APPENDIX E. 
REFERENCE 
IMAGES FOR 
HEXSEL 
SEVERITY 
RATINGS 
APPENDIX E. REFERENCE IMAGES FOR 
HEXSEL SEVERITY RATINGS  
The 2 images below are representative of a 
Hexsel score of 13, the maximum severity 
level to be included in the study. Subjects with 
cellulite severity that exceeds a Hexsel score 
of 13 should be excluded. 
[Image 1] [Image 2] 
The image below represents a Hexsel score 
>13, and depicts excessive skin laxity in the 
buttock and posterolateral thigh. Subjects with 
a Hexsel score >13 should be excluded from 
the study. 
[Image 3] 
Deleted appendix and images 

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4. 
SYNOPSIS 
Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
Title of Study: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of EN3835 in the 
Treatment of Edematous Fibrosclerotic Panniculopathy 
Lead Principal Investigator: 
Study Period:  
Estimated date first subject enrolled:  
Feb-2018 
Estimated date last subject completed:  
Oct-2018 
Phase of Development: 3 
Objectives:  
To assess the efficacy and safety of EN3835 in the treatment of edematous fibrosclerotic panniculopathy 
(EFP), commonly known as cellulite, in adult women  
Study Design: This study is a Phase 3 randomized, double-blind, placebo-controlled study of the 
efficacy and safety of EN3835 in the treatment of EFP in adult women. Subjects will be screened for 
study eligibility within 14 days prior to enrolling in this study. Subjects with 2 treatment areas (bilateral 
buttocks) (also referred to as quadrants) with moderate or severe levels of cellulite as independently 
assessed by the subject using the Patient Reported Photonumeric Cellulite Severity Scale (PR-PCSS) 
and by the Investigator using the Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 
will be eligible. The eligibility of the buttocks will be confirmed on Day 1. 
Once the eligibility of the buttocks is confirmed, subjects will be randomly assigned to a treatment 
group (EN3835 0.84 mg per buttock or placebo) in a 1:1 ratio within an investigational site. Each 
subject will receive a treatment course which consists of up to 3 treatment visits (sessions), separated by 
21 days (ie, Days 1, 22, and 43). Each treatment visit will consist of 12 injections (0.3 mL per injection 
of EN3835 0.07 mg/injection or placebo; 0.84 mg in 3.6 mL per buttock) in each of the two buttocks for 
a total volume of 7.2 mL (1.68 mg). Selection of dimples to be treated in the buttocks will be at the 
discretion of the Investigator. End of study will occur at study day 71. Of the two assigned eligible 
buttocks, one buttock will be randomly selected as the target buttock for the primary efficacy endpoint. 
The other (remaining) buttock will be considered the non-target buttock. Subjects, investigators, site 
personnel, and Endo personnel will be blinded to the identification of the target and non-target buttocks. 
At each treatment visit, each of the buttocks will be photographed before and after marking dimples and 
injection sites while the subject is in a consistent, standardized relaxed standing pose. The subject will 
assess the digital photographic image (pre-marking) of each of the buttocks using the PR-PCSS to 
determine the severity of EFP in each of the buttocks. In addition, the subject will evaluate each of the 
buttocks using a Subject Global Aesthetic Improvement Scale (S-GAIS). Subsequently, the Investigator 
will conduct live assessments of each buttock using the CR-PCSS. At Day 1, the subject will complete a 
Patient Reported Cellulite Impact Scale (PR-CIS) assessment and a Subject Self-Rating Scale (SSRS) 
assessment. The subject assessments will always be completed prior to and independently of the 
Investigator assessments at each treatment visit. In addition, the Investigator will assess each of the 
buttocks using an Investigator Global Aesthetic Improvement Scale (I-GAIS). All of the assessments 
must be done before the dimple marking. 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
At Day 71 (End of Study/Early Termination), photographs of each of the buttocks will be taken and 
evaluated by subject using the PR-PCSS. The Investigator will conduct live assessments of each of the 
buttocks using the CR-PCSS. Global assessment evaluations will be completed by both the subject and 
the Investigator. 
Number of Subjects (Planned): 420 
Study Center(s): Approximately 25 sites in United States 
Diagnosis and Inclusion/Exclusion Criteria: 
Inclusion Criteria: 
1. Voluntarily sign and date an informed consent agreement 
2. Be a female ≥18 years of age 
3. At Screening visit, have 2 bilateral buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as reported by the Investigator (CR-PCSS) 
4. At Day 1 visit, have 2 bilateral buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as reported by the Investigator (CR-PCSS) 
5. Be willing to apply sunscreen to the buttocks before each exposure to the sun while 
participating in the study (ie, Screening through end of study) 
6. Be judged to be in good health, based upon the results of a medical history, physical 
examination, and laboratory profile at Screening  
7. Have a negative serum pregnancy test at Screening and a negative urine pregnancy test before 
injection of study drug and be using a stable and effective contraception method (eg, abstinence, 
intrauterine device [IUD], hormonal [estrogen/progestin] contraceptives, or double barrier 
method) for at least 1 menstrual cycle prior to study enrollment and for the duration of the 
study; or be menopausal defined as 12 months of amenorrhea in the absence of other biological 
or physiological causes, as determined by the Investigator; or post-menopausal for at least 
1 year; or be surgically sterile  
8. Be willing and able to cooperate with the requirements of the study 
9. Be able to read, complete and understand the patient-reported outcomes rating instruments in 
English 
Exclusion Criteria: 
A subject will be excluded from study participation if she: 
1. Has any of the following systemic conditions: 
a. Coagulation disorder 
b. Evidence or history of malignancy (other than excised basal-cell carcinoma) unless there 
has been no recurrence in at least 5 years 
c. History of keloidal scarring or abnormal wound healing 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
d. Concurrent diseases or conditions that might interfere with the conduct of the study, 
confound the interpretation of the study results, or endanger the subject’s well-being. Any 
questions about concurrent diseases should be discussed with the Medical Monitor 
e. Evidence of clinically significant abnormalities on physical examination, vital signs, 
electrocardiogram (ECG), or clinical laboratory values  
2. Has any of the following local conditions in the areas to be treated: 
a. History of lower extremity thrombosis or post-thrombosis syndrome 
b. Vascular disorder (eg, varicose veins, telangiectasia) in area to be treated 
c. Inflammation or active infection 
d. Severe skin laxity, flaccidity, and/or sagging  
e. Active cutaneous alteration including rash, eczema, psoriasis, or skin cancer 
f. Has a tattoo and/or a mole located within 2 cm of the site of injection  
3. Requires the following concomitant medications before or during participation in the trial: 
a. Anticoagulant or antiplatelet medication or has received anticoagulant or antiplatelet 
medication (except for ≤150 mg aspirin daily) within 7 days before injection of study drug 
4. Has used any of the following for the treatment of EFP on a buttock within the timelines 
identified below or intends to use any of the following at any time during the course of the 
study: 
a. Liposuction in a buttock during the 12-month period before injection of study drug 
b. Injections (eg, mesotherapy); radiofrequency device treatments; laser treatment; buttock 
implant treatment; cryolipolysis; or surgery (including subcision and/or powered subcision) 
within a buttock during the 12-month period before injection of study drug 
c. Any investigational treatment for EFP on a buttock during the 12-month period before 
injection of study drug 
d. Endermologie™ or similar treatments within a buttock during the 6-month period before 
injection of study drug 
e. Massage therapy within a buttock during the 3-month period before injection of study drug 
f. Creams (eg, Celluvera™, TriLastin®) and/or home therapies to prevent or mitigate EFP 
within a buttock during the 2-week period before injection of study drug 
5. Is presently nursing or providing breast milk 
6. Intends to become pregnant during the study 
7. Intends to initiate an intensive sport or exercise program during the study 
8. Intends to initiate a weight reduction program during the study 
9. Intends to use tanning spray or tanning booths during the study 
10. Has received an investigational drug or treatment within 30 days before injection of study drug 
11. Has a known systemic allergy to collagenase or any other excipient of study drug 
12. Has received any collagenase treatments at any time prior to treatment 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
13. Was a subject in a previous cellulite clinical trial of collagenase clostridium histolyticum 
(CCH): AUX-CC-830, AUX-CC-831, EN3835-102, EN3835-104, EN3835-201, EN3835-202, 
and/or EN3835-205 
14. Any other condition(s) that, in the Investigator’s opinion, might indicate the subject to be 
unsuitable for the study 
Investigational Product, Dosage and Mode of Administration: EN3835, 1.68 mg, subcutaneous. A 
dose of 0.84 mg of EN3835 per buttock will be administered as 12 subcutaneous injections (0.3-mL 
injection administered as three 0.1-mL aliquots per injection) in each of two buttocks for a total dose of 
1.68 mg and a total volume of 7.2 mL (3.6 mL per buttock). Total number of injections will be 
24 injections per treatment visit into the two buttocks. There will be 3 treatment visits at 21 days 
intervals, ie, treatments on Days 1, 22, and 43 will be administered. 
Duration of Study: Approximately 84 days (includes screening phase) 
Screening Phase: Up to 14 days 
Criteria for Evaluation: 
Efficacy: 
• 
Subject using PR-PCSS while viewing digital image of the target buttock: 5-level scale 
ranging from 0 (no cellulite) to 4 (severe cellulite) (Day 1 (Baseline) and Days 22, 43, and 
71) for the target buttock 
• 
Subject using PR-PCSS while viewing digital image of the non-target buttock: 5-level scale 
ranging from 0 (no cellulite) to 4 (severe cellulite) (Day 1 (Baseline) and Days 22, 43, and 
71) for the non-target buttock 
• 
Investigator using the CR-PCSS by live assessment: 5-level scale ranging from 0 (no 
cellulite) to 4 (severe cellulite) (Day 1 (Baseline) and Days 22, 43, and 71) for the target 
buttock 
• 
Investigator using the CR-PCSS by live assessment: 5-level scale ranging from 0 (no 
cellulite) to 4 (severe cellulite) (Day 1 (Baseline) and Days 22, 43, and 71) for the 
non-target buttock 
• 
Investigator Global Aesthetic Improvement Scale (I-GAIS): 7-level scale ranging from 3 
(very much improved) to −3 (very much worse) (Days 22, 43, and 71) for the target buttock 
• 
Investigator Global Aesthetic Improvement Scale (I-GAIS): 7-level scale ranging from 3 
(very much improved) to −3 (very much worse) (Days 22, 43, and 71) for the non-target 
buttock 
• 
Subject Global Aesthetic Improvement Scale (S-GAIS): 7-level scale ranging from 3 (very 
much improved) to −3 (very much worse) (Days 22, 43, and 71) for the target buttock 
• 
Subject Global Aesthetic Improvement Scale (S-GAIS): 7-level scale ranging from 3 (very 
much improved) to −3 (very much worse) (Days 22, 43, and 71) for the non-target buttock 
• 
Patient Reported Cellulite Impact Scale (PR-CIS): 6 questions with responses to each 
question consisting of a numerical rating scale (NRS) ranging from 0 (Not at all) to 
10 (Extremely  

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
Analysis Populations: 
• 
The intent-to-treat (ITT) population: The ITT population is defined as all randomized 
subjects who have received at least 1 injection of study medication. 
• 
Modified intent-to-treat (mITT) population: The mITT population is defined as all  
intent-to-treat subjects with a baseline and 1 post-injection evaluation of both the CR-PCSS 
and PR-PCSS for each buttock. 
• 
Safety population: The Safety population is defined as all subjects who have received at 
least 1 injection of study medication. 
• 
Per-Protocol (PP) population: The PP population is defined as the mITT subjects without 
any of the following:  
- 
Placebo randomized subject who receives EN3835 treatment. 
- 
EN3835 randomized subject who receives placebo treatment only throughout study. 
- 
Any subject who uses protocol-prohibited medications. 
- 
Subject missing PR-PCSS and/or CR-PCSS assessment at Day 71. 
- 
Subject with a buttock not receiving all three treatment sessions without medical 
reasons (e.g., adverse events or CR-PCSS rated as zero (0)). 
- 
Subject who did not meet all inclusion and exclusion criteria. 
Analyses:  
Analyses of Primary Endpoint: 
The primary endpoint is the proportion of 2-level composite responders at Day 71 defined as subjects 
with: 
• 
an improvement in severity from baseline (Day 1 visit) of at least 2 levels of severity in the 
CR-PCSS as assessed live by the Investigator of the target buttock, and 
• 
an improvement in severity from baseline of at least 2 levels of severity in the PR-PCSS as 
assessed by the subject while viewing the digital image of the target buttock. 
A subject will be considered a responder if these criteria are met in the randomized target buttock of that 
subject. 
The primary endpoint will be summarized as percentages and analyzed using a Cochran-Mantel-
Haenszel test that compares the 2 treatment groups and adjusts for Investigator at a level of significance 
of 0.05. The ITT population will be evaluated for the primary endpoint with any subject not having an 
evaluation of CR-PCSS and/or PR-PCSS at Day 71 classified as a non-responder. 
Sensitivity analyses for the primary endpoint will include: 
• 
ITT subjects with missing data handled by multiple imputation (MI) approach 
• 
ITT subjects with missing data handled by a last observation carried forward (LOCF) 
approach 
• 
mITT subjects with missing data handled by an LOCF approach 
• 
Observed data only (no missing data imputed) 
• 
Per-protocol (PP) subjects with missing data handled by an LOCF approach if 10% or more 
subjects are excluded in the PP population from mITT population. 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
Analyses of Key Secondary Endpoints:  
There will be 8 key secondary endpoints grouped as three families of 2 to 4 endpoints per family 
analyzed in hierarchical order. 
• 
Family #1 – four endpoints: 
- 
Proportion of 1-level PR-PCSS responders defined as subjects with ≥1-level 
improvement in PR-PCSS severity rating of the target buttock at Day 71 compared to 
Day 1 
- 
Proportion of 2-level PR-PCSS responders defined as subjects with ≥2-level 
improvement in PR-PCSS severity rating of target buttock at Day 71 compared to 
Day 1 
- 
Proportion of 1-level composite responders of target buttock (defined as subjects with 
an improvement in severity from baseline of at least 1 level of severity in the CR-PCSS 
of the target buttock assessed live by the Investigator and an improvement of severity 
from baseline of at least 1 level of severity in the PR-PCSS of the target buttock) at 
Day 71 compared to Day 1 
- 
Proportion of 2-level composite responders of the non-target buttock at Day 71 
compared to Day 1 
• 
Family #2 – two endpoints: 
- 
Proportion of 1-level SSRS responders defined as subjects who were at least slightly 
satisfied at Day 71 (SSRS rating ≥ 4)  
- 
Change from baseline (Day 1) of the PR-CIS total score at Day 71 
• 
Family #3 – two endpoints: 
- 
Proportion of 1-level S-GAIS responders defined as subjects with ≥1-level 
improvement (improved, much improved or very much improved) in the S-GAIS 
assessment of the target buttock at Day 71 
- 
Proportion of 2-level S-GAIS responders defined as subjects with ≥2-level 
improvement (much improved or very much improved) in the S-GAIS assessment of 
the target buttock at Day 71 
The key secondary efficacy analyses will be analyzed in the same manner as the primary endpoint based 
on the ITT population. The family #1 key secondary efficacy analyses will be performed only if the 
primary efficacy analysis is significant at a significance level of p ≤ 0.05 (gatekeeping strategy). 
Similarly, family #2 key secondary efficacy analyses will be performed only if at least one of the key 
secondary efficacy endpoints of family #1 is significant at a significance level of p ≤ 0.0125 and 
family #3 key secondary efficacy analyses will be performed only if at least one of the key secondary 
efficacy endpoints of family #2 is significant (parallel gatekeeping strategy). Within a family of key 
secondary efficacy endpoints, the Bonferroni method will be performed to relocate unused alpha for 
testing each endpoint to assure an overall error rate of p ≤ 0.05. The details of the testing procedures will 
be provided in the statistical analysis plan for the study.  

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
Supportive Endpoints: 
The supportive variables will evaluate assessments at various study time points and using various 
populations.  
• 
Proportion of 2-level PR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 2 levels of severity in the PR-PCSS) of the target buttock 
(Days 22, 43, and 71) 
• 
Proportion of 2-level PR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 2 levels of severity in the PR-PCSS) of the non-target 
buttock (Days 22, 43, and 71) 
• 
Proportion of 1-level PR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 1 level of severity in the PR-PCSS) of the target buttock 
(Days 22, 43, and 71) 
• 
Proportion of 1-level PR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 1 level of severity in the PR-PCSS) of the non-target 
buttock (Days 22, 43, and 71) 
• 
Proportion of 2-level PR-PCSS responders of at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if this criterion is met in the target buttock or 
non-target buttock or both buttocks in that subject. 
• 
Proportion of 1-level PR-PCSS responders of at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if this criterion is met in the target buttock or 
non-target buttock or both buttocks in that subject.  
• 
Proportion of 2-level PR-PCSS responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both the 
target and non-target buttocks. 
• 
Proportion of 1-level PR-PCSS responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both the 
target and non-target buttocks. 
• 
Proportion of 2-level CR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 2 levels of severity in the CR-PCSS) of the target buttock 
(Days 22, 43, and 71)  
• 
Proportion of 2-level CR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 2 levels of severity in the CR-PCSS) of the non-target 
buttock (Days 22, 43, and 71) 
• 
Proportion of 1-level CR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 1 level of severity in the CR-PCSS) of the target buttock 
(Days 22, 43, and 71) 
• 
Proportion of 1-level CR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 1 level of severity in the CR-PCSS) of the non-target 
buttock (Days 22, 43, and 71 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
• 
Proportion of 2-level CR-PCSS responders of at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if this criterion is met in the target buttock or 
non-target buttock or both buttocks in that subject 
• 
Proportion of 1-level CR-PCSS responders of at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if this criterion is met in the target buttock or 
non-target buttock or both buttocks in that subject 
• 
Proportion of 2-level CR-PCSS responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both the 
target and non-target buttocks 
• 
Proportion of 1-level CR-PCSS responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both the 
target and non-target buttocks 
• 
Proportion of 1-level composite responders of the target buttock (defined as subjects with 
an improvement in severity from baseline of at least 1 level of severity in the CR-PCSS of 
the target buttock assessed live by the Investigator and an improvement of severity from 
baseline of at least 1 level of severity in the PR-PCSS of that same target buttock) (Days 22, 
43, and 71) 
• 
Proportion of 1-level composite responders of the non-target buttock (defined as subjects 
with an improvement in severity from baseline of at least 1 level of severity in the 
CR-PCSS of the non-target buttock assessed live by the Investigator and an improvement of 
severity from baseline of at least 1 level of severity in the PR-PCSS of that same non-target 
buttock) (Days 22, 43, and 71) 
• 
Proportion of 1-level composite responders of at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if this criterion is met in the target buttock or 
non-target buttock or both buttocks in that subject. 
• 
Proportion of 1-level composite responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met in 
both the target and non-target buttocks. 
• 
Proportion of 2-level composite responders of the target buttock (defined as subjects with 
an improvement in severity from baseline of at least 2 levels of severity in the CR-PCSS of 
the target buttock assessed live by the Investigator and an improvement of severity from 
baseline of at least 2 levels of severity in the PR-PCSS of that same target buttock) 
(Days 22, 43, and 71) 
• 
Proportion of 2-level composite responders of the non-target buttock (defined as subjects 
with an improvement in severity from baseline of at least 2 levels of severity in the 
CR-PCSS of the non-target buttock assessed live by the Investigator and an improvement of 
severity from baseline of at least 2 levels of severity in the PR-PCSS of that same non-target 
buttock) (Days 22, 43, and 71) 
• 
Proportion of 2-level composite responders of at least one of two buttocks (Days 22, 43, 
and 71). A subject will be considered a responder if this criterion is met in the target buttock 
or non-target buttock or both buttocks in that subject. 

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Name of Active Ingredient: Collagenase clostridium histolyticum 
• 
Proportion of 2-level composite responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met in 
both the target and non-target buttocks. 
• 
Proportion of subjects at each level of the S-GAIS of the target buttock (Days 22, 43, and 
71) 
• 
Proportion of subjects at each level of the S-GAIS of the non-target buttock (Days 22, 43, 
and 71) 
• 
Proportion of 1-level S-GAIS responders defined as subjects with a response of at least 1 
(improved) in the S-GAIS of the target buttock (Days 22, 43, and 71) 
• 
Proportion of 1-level S-GAIS responders defined as subjects with a response of at least 1 
(improved) in the S-GAIS of the non-target buttock (Days 22, 43, and 71) 
• 
Proportion 1-level S-GAIS responders of at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if this criterion is met in the target buttock or 
non-target buttock or both buttocks in that subject. 
• 
Proportion of 1-level S-GAIS responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both the 
target and non-target buttocks. 
• 
Proportion of subjects at each level of the I-GAIS of the target buttock (Days 22, 43, and 
71) 
• 
Proportion of subjects at each level of the I-GAIS of the non-target buttock (Days 22, 43, 
and 71) 
• 
Proportion of 1-level I-GAIS responders defined as subjects with a response of at least 1 
(improved) in the I-GAIS of the target buttock (Days 22, 43, and 71) 
• 
Proportion of I-level S-GAIS responders defined as subjects with a response of at least 1 
(improved) in the I-GAIS of the non-target buttock (Days 22, 43, and 71) 
• 
Proportion of 1-level I-GAIS responders of at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if this criterion is met in the target buttock or 
non-target buttock or both buttocks in that subject.  
• 
Proportion of 1-level I-GAIS responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both the 
target and non-target buttocks. 
• 
Change from baseline (Day 1) of the PR-CIS score at Day 71 
• 
Change from baseline (Day 1) of the abbreviated PR-CIS score at Day 71 
• 
Proportion of subjects with a change from baseline (Day1) of the PR-CIS ≥12 at Day 71 
• 
Proportion of subjects with a change from baseline (Day 1) of the abbreviated PR-CIS ≥10 
at Day 71 
• 
Proportion of subjects at each level of the subject self-rating scale (SSRS) (Day 1 (Baseline) 
and Day 71 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
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Name of Active Ingredient: Collagenase clostridium histolyticum 
• 
Proportion of 1-level SSRS responders defined as subjects who were at least slightly 
satisfied at Day 71 (SSRS rating ≥ 4) 
• 
Proportion of subjects at each level of the subject satisfaction with cellulite treatment 
assessment (Day 71) 
• 
Proportion of satisfied responders (defined as subjects with a response of at least 1 
(ie, 1-Satisfied or 2-Very Satisfied) in the subject satisfaction with cellulite treatment 
assessment (Day 71) 
All supportive endpoints will be summarized as percentages. The dichotomous secondary endpoints 
(ie, responder endpoints) will be analyzed using a Cochran-Mantel-Haenszel test adjusted for 
Investigator. Changes in the PR-PCSS ratings and CR-PCSS ratings from baselines, S-GAIS scores, and 
I-GAIS scores will be analyzed using the Mann-Whitney test. 
Safety Analysis: 
The following variables are safety endpoints: 
• 
AEs: Mapped to preferred term using the Medical Dictionary for Regulatory Activities 
(MedDRA) 
• 
Vital signs 
• 
Clinical laboratory tests 
AEs will be summarized by proportion of subjects reporting each event. The Fisher exact test will be 
used to compare EN3835 to placebo. Descriptive statistics will be presented for actual and change from 
baseline at each visit for vital signs and for each clinical laboratory test parameter. The comparison 
between treatment groups will be based on the change from baseline for clinical laboratory tests and 
vital signs using an analysis of variance (ANOVA) with a factor of drug (EN3835 or placebo). 
Immunogenicity: Anti-AUX-I and anti-AUX-II antibody levels will be summarized using descriptive 
statistics for the actual value at the visit. Samples from Day 1, Day 22, Day 43, and Day 71 visits will be 
analyzed for anti-AUX-I and anti-AUX-II antibodies and a subset of Day 1 and Day 71 samples will be 
analyzed for neutralizing antibodies. 
 

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5. 
SCHEDULE OF EVENTS 
Procedures 
Day -14 to -1 
 
Screening 
Day 1 
Treatment  
Visit 1 
Day 22 (± 3 d) 
Treatment  
Visit 2 
Day 43 (± 3 d) 
Treatment  
Visit 3 
Day 71 (+ 5 d) / 
End of Study / 
Early Termination 
Unscheduled 
Clinic Visita 
Informed consent 
X 
 
 
 
 
 
Inclusion/exclusion 
X 
 
 
 
 
 
Digital photography 
X 
Xb 
Xb 
Xb 
X 
X 
Medical history/EFP history including previous 
treatments 
X 
 
 
 
 
 
Prior/concomitant medications/procedures 
X 
X 
X 
X 
X 
X 
Physical examination: 
X 
 
 
 
 
 
• Body weight 
X 
 
Xc 
Xc 
X 
X 
• Height  
X 
 
 
 
 
 
• Fitzpatrick skin type 
X 
 
 
 
 
 
Vital signs 
X 
Xd 
Xd 
Xd 
X 
X 
12-lead ECG 
X 
 
 
 
 
 
Collection of samples: 
• Clinical laboratory 
X 
 
 
 
X 
X 
• Anti-AUX-I/anti-AUX-II antibody level 
 
Xc 
Xc 
Xc 
X 
 
• Pregnancy testing 
Xe 
Xc,e 
Xc,e 
Xc,e 
Xe 
X 
Subject cellulite assessmentsf: 
• Patient Reported Photonumeric Cellulite 
Severity Scale (PR-PCSS) 
Xg,h 
Xc,g,h 
Xc,g,h 
Xc,g,h 
Xg,h 
 
• Subject Global Aesthetic Improvement 
(S-GAIS) 
 
 
Xc,g,h 
Xc,g,h 
Xg,h 
 
• Patient Reported Cellulite Impact Scale 
(PR-CIS) 
 
Xc,g 
 
 
Xg 
 
• Subject Satisfaction With Cellulite Treatment 
Assessment 
 
 
 
 
Xg 
 
• Subject Self-Rating Scale (SSRS) 
 
Xc 
 
 
X 
 

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Procedures 
Day -14 to -1 
 
Screening 
Day 1 
Treatment  
Visit 1 
Day 22 (± 3 d) 
Treatment  
Visit 2 
Day 43 (± 3 d) 
Treatment  
Visit 3 
Day 71 (+ 5 d) / 
End of Study / 
Early Termination 
Unscheduled 
Clinic Visita 
Investigator cellulite assessments: 
• Selection of dimples to be treated within the 
two buttocks 
 
Xc 
Xc 
Xc 
 
 
• Marking the dimples and injection sites to be 
treated within the buttocks 
 
Xc 
Xc 
Xc 
 
 
• Clinician Reported Photonumeric Cellulite 
Severity Scale (CR-PCSS) 
X 
Xc,h 
Xc,h 
Xc,h 
Xh 
 
• Investigator Global Aesthetic Improvement 
(I-GAIS)  
 
 
Xc,h 
Xc,h 
Xc,h 
 
Confirm eligibility 
 
Xc 
 
 
 
 
Randomize to treatment 
 
Xc,i 
 
 
 
 
Study drug administration 
 
X 
X 
X 
 
 
Injection site reactions/local tolerability in the 
buttocks 
 
X 
X 
X 
X 
X 
Adverse events 
Monitored Throughout Study 
a During unscheduled visits, the Investigator or designee may perform any study procedure that they deem clinically necessary (eg, vital signs, clinical lab assessments, and 
pregnancy test). 
b Before and after marking the dimples and injection sites. 
c Before injection. 
d Up to 4 hours before injection; approximately 15 and 30 minutes after injection. Vital signs must be stable before the subject is discharged. 
e Serum pregnancy test on Screening visit and Day 71/EOS visit; urine pregnancy test on Day 1, Day 22, and Day 43 visits. 
f Subject assessments should be completed independently and prior to Investigator assessments at each visit. 
g Assessment made via photographs (if treatment visit, use photographs taken before marking dimples and injection sites). 
h Assessment of each of the 2 buttocks independently. 
i Before randomization, each of the subject’s buttocks must have ratings of 3 or 4 (moderate or severe) in both the CR-PCSS and PR-PCSS. 
NOTE: Subject cellulite assessments must be completed before the Investigator cellulite assessments are conducted at each visit.  
d=Days; ECG=Electrocardiogram; EFP=Edematous fibrosclerotic panniculopathy; EOS=End of study 

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6. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES 
TABLE OF CONTENTS 
1. 
TITLE PAGE ................................................................................................................1 
2. 
SUMMARY OF CHANGES ........................................................................................2 
3. 
SPONSOR CONTACT INFORMATION .................................................................31 
4. 
SYNOPSIS .................................................................................................................32 
5. 
SCHEDULE OF EVENTS .........................................................................................43 
6. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............45 
7. 
LIST OF ABBREVIATIONS .....................................................................................51 
8. 
INTRODUCTION ......................................................................................................52 
8.1. 
Background .................................................................................................................52 
8.1.1. 
Edematous Fibrosclerotic Panniculopathy .................................................................52 
8.1.2. 
Current EFP Treatments .............................................................................................52 
8.1.3. 
EN3835 (Collagenase Clostridium Histolyticum) ......................................................53 
8.2. 
Summary of Nonclinical Studies ................................................................................54 
8.3. 
Summary of Known Risks and Benefits .....................................................................54 
8.4. 
Rationale .....................................................................................................................55 
9. 
OBJECTIVES .............................................................................................................56 
9.1. 
Primary Objective .......................................................................................................56 
9.2. 
Secondary Objectives .................................................................................................56 
9.3. 
Exploratory Objectives ...............................................................................................56 
10. 
INVESTIGATIONAL PLAN .....................................................................................57 
10.1. 
Study Design ...............................................................................................................57 
10.2. 
Selection of Doses ......................................................................................................57 
10.3. 
Study Drug Administration .........................................................................................58 
10.4. 
Care Procedures After Injection .................................................................................60 
10.5. 
Discussion of Study Design, Including the Choice of Control Groups ......................60 
11. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................61 
11.1. 
Subject Inclusion Criteria ...........................................................................................61 
11.2. 
Subject Exclusion Criteria ..........................................................................................61 
11.3. 
Subject Discontinuation Criteria .................................................................................63 

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11.3.1. 
Replacement Procedures .............................................................................................63 
12. 
TREATMENT OF SUBJECTS ..................................................................................64 
12.1. 
Study Visits .................................................................................................................64 
12.1.1. 
Informed Consent .......................................................................................................64 
12.1.2. 
Subject Screening .......................................................................................................64 
12.1.2.1. 
Medical History ..........................................................................................................64 
12.1.2.2. 
Screening Period (Day -14 to Day -1) ........................................................................64 
12.2. 
Selecting and Marking Dimples during Treatment Visits ..........................................65 
12.3. 
Digital Photography during Treatment Visits 1, 2, and 3 ...........................................66 
12.4. 
Treatment Visit 1 (Day 1) ...........................................................................................67 
12.4.1. 
Treatment Visit 1: Pre-Injection .................................................................................67 
12.4.2. 
Treatment Visit 1: Injection and Post-injection ..........................................................68 
12.5. 
Treatment Visit 2 (Day 22 [±3 days]) and Treatment Visit 3 (Day 43 
[±3 days]) ....................................................................................................................68 
12.5.1. 
Treatment Visits 2 and 3: Pre-injection ......................................................................68 
12.5.2. 
Treatment Visits 2 and 3: Injection and Post-injection ..............................................69 
12.6. 
Day 71 (+5 days) / End of Study / Early Termination ................................................69 
12.7. 
Unscheduled Visits .....................................................................................................70 
12.8. 
Prior and Concomitant Medications and Procedures ..................................................70 
12.8.1. 
Prohibited Medications or Procedures ........................................................................70 
12.9. 
Treatment Compliance ................................................................................................70 
12.10. 
Blinding and Randomization ......................................................................................70 
13. 
ASSESSMENT OF EFFICACY ................................................................................72 
13.1. 
Efficacy Measurements ..............................................................................................72 
13.1.1. 
Digital Photography ....................................................................................................72 
13.1.2. 
Subject and Investigator Cellulite Assessments .........................................................72 
13.1.2.1. 
Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) ........................72 
13.1.2.2. 
Subject Global Aesthetic Improvement Scale (S-GAIS) ............................................73 
13.1.2.3. 
Patient Reported Cellulite Impact Scale (PR-CIS) .....................................................74 
13.1.2.4. 
Subject Satisfaction with Cellulite Treatment Assessment ........................................74 
13.1.2.5. 
Subject Self-Rating Scale (SSRS) ..............................................................................75 
13.1.2.6. 
Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) ....................75 
13.1.2.7. 
Investigator Global Aesthetic Improvement Scale (I-GAIS) .....................................76 

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14. 
ASSESSMENT OF SAFETY .....................................................................................77 
14.1. 
Definitions ..................................................................................................................77 
14.1.1. 
Adverse Events ...........................................................................................................77 
14.1.2. 
Serious Adverse Events ..............................................................................................77 
14.2. 
Monitoring Adverse Events ........................................................................................78 
14.3. 
Relationship to Study Drug ........................................................................................78 
14.4. 
Intensity Assessment ..................................................................................................79 
14.5. 
Reporting Adverse Events and Serious Adverse Events ............................................79 
14.5.1. 
Reporting Adverse Events ..........................................................................................79 
14.5.2. 
Reporting Serious Adverse Events .............................................................................79 
14.5.2.1. 
Follow-up Procedures for Serious Adverse Events ....................................................80 
14.6. 
Special Reporting Situations .......................................................................................80 
14.6.1. 
Adverse Events of Special Interest .............................................................................80 
14.6.2. 
Overdose/Misuse/Abuse .............................................................................................80 
14.6.2.1. 
Overdose .....................................................................................................................80 
14.6.3. 
Pregnancy ...................................................................................................................81 
14.6.4. 
AEs/SAEs Experienced by Non-subjects Exposed to Study Medication ...................81 
14.7. 
Clinical Laboratory Determinations ...........................................................................81 
14.8. 
Anti-AUX-I and Anti-AUX-II Antibodies .................................................................83 
14.9. 
Vital Signs ..................................................................................................................83 
14.10. 
Electrocardiogram .......................................................................................................83 
14.11. 
Physical Examination .................................................................................................84 
14.12. 
Other Safety Assessments ...........................................................................................84 
15. 
ASSESSMENT OF PHARMACOKINETICS ...........................................................85 
16. 
ASSESSMENT OF PHARMACODYNAMICS ........................................................86 
17. 
STATISTICAL CONSIDERATIONS AND METHODS .........................................87 
17.1. 
Determination of Sample Size ....................................................................................87 
17.2. 
Subject Populations ....................................................................................................88 
17.2.1. 
Safety Population ........................................................................................................88 
17.2.2. 
Intent-to-Treat (ITT) Population .................................................................................88 
17.2.3. 
Modified Intent-to-Treat (mITT) Population ..............................................................88 
17.2.4. 
Per-Protocol (PP) Population ......................................................................................88 
17.3. 
Subject Disposition .....................................................................................................88 

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17.4. 
Demographics and Other Baseline Characteristics .....................................................89 
17.5. 
Efficacy Analyses .......................................................................................................89 
17.5.1. 
Primary Efficacy Variable ..........................................................................................90 
17.5.2. 
Secondary Efficacy Variables .....................................................................................90 
17.5.2.1. 
Key Secondary Variables ...........................................................................................90 
17.5.3. 
Supportive Efficacy Variables ....................................................................................91 
17.5.3.1. 
Supportive Variables ..................................................................................................91 
17.6. 
Safety Analyses ..........................................................................................................95 
17.6.1. 
Prior, Concomitant, and Follow-up Medication .........................................................95 
17.6.2. 
Study Drug Exposure ..................................................................................................95 
17.6.3. 
Measurement of Treatment Compliance ....................................................................95 
17.6.4. 
Adverse Events ...........................................................................................................95 
17.6.5. 
Vital Signs ..................................................................................................................96 
17.6.6. 
Clinical Laboratory Parameters ..................................................................................96 
17.6.7. 
Electrocardiogram .......................................................................................................97 
17.6.8. 
Physical Examination .................................................................................................97 
17.6.9. 
Other Safety Measurements ........................................................................................97 
17.7. 
Pharmacokinetic Analyses ..........................................................................................97 
17.8. 
Pharmacodynamic Analyses .......................................................................................97 
17.9. 
Other Data (eg, Health Economics/QOL, Pharmacogenetic, etc.) .............................97 
17.10. 
Interim Analysis ..........................................................................................................97 
17.11. 
Statistical Software .....................................................................................................97 
18. 
STUDY DRUG MATERIALS AND MANAGEMENT ...........................................98 
18.1. 
Study Drug Identity ....................................................................................................98 
18.2. 
Study Drug Packaging and Labeling ..........................................................................98 
18.3. 
Study Drug Storage .....................................................................................................98 
18.4. 
Study Drug Preparation ..............................................................................................98 
18.5. 
Study Drug Accountability .........................................................................................99 
18.5.1. 
Study Drug Handling and Disposal ............................................................................99 
19. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS .......................................100 
19.1. 
Source Documents ....................................................................................................100 
19.2. 
Study Monitoring ......................................................................................................100 
19.3. 
Audits and Inspections ..............................................................................................100 

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19.4. 
Institutional Review Board (IRB) .............................................................................100 
19.5. 
Data Recording and Documentation .........................................................................101 
20.
QUALITY CONTROL AND QUALITY ASSURANCE .......................................102
21.
ETHICS ....................................................................................................................103
21.1. 
Ethics Review ...........................................................................................................103 
21.2. 
Ethical Conduct of the Study ....................................................................................103 
21.3. 
Subject Information and Consent .............................................................................104 
22.
DATA HANDLING AND RECORDKEEPING .....................................................105
22.1. 
Data Collection .........................................................................................................105 
22.2. 
Study Documentation ...............................................................................................105 
23.
REPORTING AND PUBLICATION .......................................................................106
24.
INVESTIGATOR OBLIGATIONS .........................................................................107
24.1. 
Regulatory Documents .............................................................................................107 
24.2. 
Delegation of Responsibilities and Adequate Resources .........................................108 
24.3. 
Medical Care of Study Subjects ...............................................................................108 
24.4. 
Use of Investigational Materials ...............................................................................108 
24.5. 
Retention of Records ................................................................................................108 
24.6. 
Subject Confidentiality .............................................................................................109 
25.
TERMINATION OF STUDY ..................................................................................110
26.
INVESTIGATOR’S STATEMENT .........................................................................111
27.
REFERENCES .........................................................................................................112
APPENDIX A. DOCUMENTS REQUIRED PRIOR TO INITIATION OF THE 
STUDY ...........................................................................................................113 
APPENDIX B. PATIENT-REPORTED PHOTONUMERIC CELLULITE SEVERITY 
SCALE (PR-PCSS) FOR THE BUTTOCK ....................................................115 
APPENDIX C. CLINICIAN-REPORTED PHOTONUMERIC CELLULITE 
SEVERITY SCALE (CR-PCSS) FOR THE BUTTOCK ...............................116 
APPENDIX D. PATIENT REPORTED CELLULITE IMPACT SCALE (PR-CIS) ..............117 

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LIST OF TABLES 
Table 1: 
Sponsor Contact Information ......................................................................................31 
Table 2: 
Abbreviations and Special Terms ...............................................................................51 
Table 3: 
Study Treatment Groups .............................................................................................57 
Table 4: 
Concomitant Medication Restrictions for Subjects during the Treatment 
Phase of Study ............................................................................................................70 
Table 5: 
Subject Global Aesthetic Improvement Scale (S-GAIS) ............................................74 
Table 6: 
Subject Satisfaction with Cellulite Treatment Assessment - Buttocks .......................74 
Table 7: 
Subject Self-Rating Scale (SSRS) ..............................................................................75 
Table 8: 
Investigator Global Aesthetic Improvement Scale (I-GAIS) .....................................76 
Table 9: 
Clinical Laboratory Tests ...........................................................................................82 
Table 10: Vital Signs Measurements on Injection Day ..............................................................83 
Table 11: Fitzpatrick Scale .........................................................................................................84 
Table 12: Previous Results as Basis for Sample Size .................................................................87 
 
LIST OF FIGURES 
Figure 1: 
Study Design ...............................................................................................................57 
Figure 2: 
Study Drug Administration at Each Injection Site .....................................................59 
 
 

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7. 
LIST OF ABBREVIATIONS  
The following abbreviations and specialized terms are used in this study protocol. 
Table 2: 
Abbreviations and Special Terms 
Abbreviation 
Definition 
AE 
Adverse event 
AUX-I 
Clostridial class I collagenase 
AUX-II 
Clostridial class II collagenase 
BMI 
Body mass index 
CR-PCSS 
Clinician Reported Photonumeric Cellulite Severity Scale 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
EFP 
Edematous fibrosclerotic panniculopathy 
ePRO 
Electronic patient reported outcome 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HREC 
Human Research Ethics Committee 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
I-GAIS 
Investigator-Global Aesthetic Improvement Scale 
IRB 
Institutional Review Board 
ITT 
Intent-to-treat 
IWRS 
Interactive web response system 
LOCF 
Last observation carried forward 
MI 
Multiple imputation 
mITT 
Modified intent-to-treat 
PR-CIS 
Patient Reported Cellulite Impact Scale 
PR-PCSS 
Patient Reported Photonumeric Cellulite Severity Scale 
Quadrant 
A quadrant is a treatment area 
Qualified designee 
Qualified by education and training to perform the study procedure (eg, 
sub-Investigator, nurse). 
SAE 
Serious adverse event 
S-GAIS 
Subject – Global Aesthetic Improvement Scale 
SSRS 
Subject Self-Rating Scale 
TEAE 
Treatment-emergent adverse event. Adverse events that occur on or after the 
first injection of study drug. 

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8. 
INTRODUCTION 
8.1. 
Background 
8.1.1. 
Edematous Fibrosclerotic Panniculopathy 
Edematous fibrosclerotic panniculopathy (EFP), commonly known as cellulite, has been defined 
as a local metabolic disorder of subcutaneous tissues that results in a contour abnormality of the 
skin.(1) The condition manifests as dimpled skin, particularly in the gluteal-femoral region.(2,3) 
EFP is caused by herniation of subcutaneous fat lobules through the dermohypodermal junction 
and/or shortening of the collagen septa that cross the hypodermal layer and connects the dermis 
to the underlying fascia. This creates an uneven surface with dimpling.(1,2) EFP is a medical 
condition resulting in a potentially cosmetically unacceptable alteration of the skin, and affects 
an estimated 85% to 98% of postpubertal women.(1,3) 
The pathophysiology of EFP is not completely understood, but there are 3 main theories: edema 
resulting from excessive hydrophilia of the intercellular matrix, alteration of the regional 
microcirculation, and different anatomical conformation of collagenous subcutaneous tissues in 
women versus men.(4) 
It is known that EFP is different from generalized obesity. In generalized obesity, adipocytes 
undergo hypertrophy and hyperplasia that are not limited to the pelvis, thighs, and abdomen.(1) 
In areas of EFP, adipocytes have physiologic and biochemical properties that differ from adipose 
tissue located elsewhere. Large, metabolically-stable adipocytes characterize EFP-prone areas; 
thus, the responsiveness to catecholamine-induced lipolysis is less in EFP tissues compared to 
visceral fat, which has the greatest responsiveness.(1) 
Subcutaneous fat lobes are separated from one another by thin, usually rigid strands of 
collagenous connective tissues, which cross the fatty layers and connect the dermis to the 
underlying fascia. These septa stabilize the subcutis and divide the fat. In EFP, shortening of the 
collagen septa due to fibrosis provokes retraction at the insertion points of the trabeculae, 
causing the depressions that characterize EFP.(2) There are a higher percentage of thinner, 
perpendicular hypodermal septa in women with EFP than in men.(1) Weight gain makes EFP 
more noticeable, but it may be present even in thin subjects. Genetics may also play a role since 
EFP tends to run in families. 
8.1.2. 
Current EFP Treatments 
There are therapies that have been utilized in an attempt to treat cellulite; however, there are no 
approved pharmacologic treatments. Despite multiple therapeutic modalities, there is little 
scientific evidence that any of these treatments are beneficial. In fact, much of the evidence is 
anecdotal, subjective, or based only on patient self-assessment.(5) Some of the historical 
treatments for EFP have included weight loss,(6) topical agents,(5) massage,(7) liposuction,(5,6) 
mesotherapy,(6) radiofrequency,(6) subcision and powered subcision,(8) and laser 
therapies;(9,10) some of these treatments may pose an increased risk for adverse effects.(5) 

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There remains an unmet medical need for safe and effective therapies to improve the aesthetic 
outcome in women with cellulite. To effectively treat cellulite, a therapeutic approach may 
require disruption of the dermal septa, which are composed of collagen and cause the skin 
dimpling that is bothersome to many women. 
8.1.3. 
EN3835 (Collagenase Clostridium Histolyticum) 
Endo Pharmaceuticals Inc. (Endo) is developing EN3835 for the treatment of EFP. Because 
EN3835 is a proteinase that can hydrolyze the triple-helical region of collagen under 
physiological conditions, EN3835 has the potential to be effective in lysing subdermal collagen, 
such as those observed in the dermal septa, which are the underlying cause of the skin dimpling 
in women with EFP. EN3835 targets the collagenase structural matrix (eg, dermal septa) at the 
site of injection and does not require systemic exposure to be effective. 
EN3835 is a parenteral lyophilized product comprised of 2 collagenases in an approximate 1:1 
mass ratio, Collagenase I (AUX-I, Clostridial class I collagenase) and Collagenase II (AUX-II; 
Clostridial class II collagenase). These collagenases are isolated and purified from the 
fermentation of Clostridium histolyticum. 
Collagenase AUX-I is a single polypeptide chain containing approximately 1,000 amino acids of 
known sequence and with a molecular weight of 114 kDa. Collagenase AUX-II is also 
approximately 1,000 amino acids long and has a molecular weight of 113 kDa. These 
2 collagenases are not immunologically cross-reactive and have different specificities, such that 
together they become synergistic, providing a very broad hydrolyzing reactivity toward collagen. 
Clostridial collagenases are proteinases that can hydrolyze the triple-helical region of collagen 
under physiological conditions. 
EN3835 is currently approved (brand name is XIAFLEX®) for: 1) the treatment of adults with 
Dupuytren’s contracture with a palpable cord and, 2) for the treatment of adult men with 
Peyronie’s disease with a palpable plaque and curvature deformity of at least 30° at the start of 
therapy. 
A recent Phase 2b, randomized, double-blind, placebo-controlled study (EN3835-201) of 
375 women randomized to treatment of one treatment area (quadrant) (quadrant was defined in 
study EN3835-201 as a left buttock, a right buttock, a left posterolateral thigh or a right 
posterolateral thigh) of cellulite with EN3835 0.84 mg or placebo in a 1:1 ratio assessed the 
effectiveness and safety of EN3835. Efficacy in this study was evaluated based on cellulite 
assessments using Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS), Patient 
Reported Photonumeric Cellulite Severity Scale (PR-PCSS), Investigator Global Aesthetic 
Improvement Scale (GAIS-I), Subject Global Aesthetic Improvement Scale (GAIS-S), and 
Subject Satisfaction with Cellulite Treatment. 
Results from the Phase 2b study demonstrated that treatment (3 visits approximately 21 days 
apart) improved the cellulite severity of the treatment area as assessed by the primary endpoint of 
2-level composite responder analyses, the proportion of responders based on an improvement of 
≥2 levels in the appearance of cellulite in both the patient PR-PCSS and the clinician CR-PCSS 
of buttocks and thighs was statistically significantly greater in subjects who received EN3835 
0.84 mg (10.6%; p<0.001) compared to subjects who received placebo (1.6%); 1-level (or 
greater) responders in the PR-PCSS of EN3835-treated subjects (72.3%) was significantly 

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greater than 1-level responders in the placebo group (51.6%) (p<0.001); statistically significant 
(p≤0.001) improvement in the appearance of cellulite based on the subject S-GAIS were 
observed in EN3835 0.84-mg group (73.1%) compared to the placebo group (44.0%); and 62.9% 
of subjects in the EN3835 0.84 mg group were satisfied or very satisfied with the results of their 
cellulite treatment compared with only 35.9% of subjects in the placebo group (p<0.001). In 
subjects treated in buttocks (n=187), the proportion of 2-level composite responders was 
statistically significantly greater in subjects who received EN3835 0.84 mg (14.9%; p<0.001) 
compared to subjects who received placebo (1.1%); 1-level (or greater) responders in the 
PR-PCSS of EN3835-treated subjects (72.7%) was significantly greater than 1-level responders 
in the placebo group (47.8%) (p<0.001). 
The study also demonstrated EN3835 to be well tolerated with no serious adverse events (SAEs) 
related to EN3835. Safety results from a total of 4 studies (1 pilot, 2 Phase 1, and 2 Phase 2 
studies) in which 435 adult females received subcutaneous injections of EN3835 indicate that the 
majority of treatment-emergent adverse events (TEAEs) are transient, non-serious, mild or 
moderate in intensity, and related to the local administration of EN3835. The immunogenicity 
profile after 3 treatment visits of EN3835 indicate that greater than 90% of EN3835-treated 
subjects were seropositive for AUX-I and/or AUX-II antibodies; this profile of EN3835 is 
similar to that observed in the Dupuytren’s contracture and Peyronie’s disease programs. 
A Phase 1, open-label safety and pharmacokinetic study of a single dose of EN3835 0.84 mg in 
11 female subjects with EFP showed that there was no quantifiable levels of AUX-I or AUX-II 
at any time point after subcutaneous injection of EN3835 0.84 mg into one quadrant. A second 
Phase 1, open-label safety and pharmacokinetic study of a single dose of EN3835 0.84 mg per 
treatment area in two treatment areas (buttock-buttock, thigh-thigh, or buttock-thigh) 
concurrently (total dose of 1.68 mg) showed that there was no quantifiable levels of AUX-I or 
AUX-II at any time point post-dose attributable to the injection of EN3835 1.68 mg. 
The results from these studies suggest that subcutaneous injections of EN3835 in the area of 
cellulite may be a well-tolerated and effective medical treatment for adults with EFP. 
8.2. 
Summary of Nonclinical Studies 
Non-clinical studies necessary to support clinical studies have been performed and are 
summarized in the Investigator Brochure (IB).(11) Non-clinical studies in the following areas 
were performed: toxicology, reprotoxicity, genotoxicity, and hypersensitivity. 
8.3. 
Summary of Known Risks and Benefits 
A summary of safety risks is provided in the IB.(11) The following events have been commonly 
observed: local injection site reactions (injection site bruising, injection site swelling, injection 
site pain) for the various approved indications as well as those being investigated. In the phase 
2b study of EN3835 in women with EFP, the following treatment related adverse events ≥2% of 
189 EN3835-treated women were reported: injection site bruising (75.1%), injection site pain 
(59.3%), injection site nodule (14.3%), injection site pruritus (11.1%), injection site swelling 
(7.4%), injection site induration (5.8%), injection site mass (5.3%), injection site discolouration 
(3.2%), and injection site erythema (2.1%). These events are similar to events reported in the 
clinical trials of EN3835 for the approved indications. Postmarketing safety data are consistent 
with safety data reported in clinical trials. 

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Although a thorough benefit of EN3835 has not been fully evaluated in the treatment of EFP, the 
efficacy results from the Phase 2b study and previous EFP studies warranted further 
development. 
8.4. 
Rationale 
The results from the Phase 2b EFP study (EN3835-201) further suggested that EN3835 0.84 mg 
per treatment area (quadrant) is an effective treatment of EFP based on improvement in the 
severity of cellulite as determined by the Investigator and the subject. There were no safety 
concerns following 0.84 mg per treatment area in the treatment of EFP (section 8.1.3). Safety 
findings from the Phase 2b EFP study are similar to that observed in previous clinical studies 
with EN3835 in the treatment of EFP and XIAFLEX in the treatment of Dupuytren’s contracture 
and Peyronie’s disease, in that that the majority of AEs occurred at the site of injection and 
resolved before the next scheduled treatment. The immunogenicity profile of EN3835 in the 
Phase 2b EFP study is similar in previous studies and programs. 
Based on the efficacy and safety findings from the Phase 2a and 2b EFP studies, the EN3835 
0.84-mg dose per treatment area in two treatment areas (buttocks) warranted further investigation 
in this study. 
Treating two buttocks at each treatment visit will potentially provide a symmetrical-like 
improvement in appearance. Support for evaluation of the treatment of two buttocks concurrently 
is based on: 1) the safety findings from the previous EFP studies are local to the injection site, 
2) the pharmacological activity of EN3835 is local and does not require systemic exposure, and 
3) no significant quantifiable systemic concentration has been attributable to injection of two 
buttocks concurrently. 
The integration of dose and use justification supports this study of evaluation of EN3835 
0.84 mg per treatment area in two treatment areas (buttocks) concurrently. 
 

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9. 
OBJECTIVES 
9.1. 
Primary Objective 
The primary objective of this study is to assess the efficacy and safety of EN3835 in the 
treatment of edematous fibrosclerotic panniculopathy (EFP) commonly known as cellulite in 
adult women. 
9.2. 
Secondary Objectives 
There are no secondary objectives of this study. 
9.3. 
Exploratory Objectives 
There are no exploratory objectives of this study. 
 

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10. 
INVESTIGATIONAL PLAN 
10.1. 
Study Design 
This study will be performed at approximately 25 study centers located in the United States. This 
clinical study will be conducted as a multicenter, randomized, double-blind, placebo-controlled 
study comparing EN3835 to placebo in adult women with EFP. The study will consist of 71 days 
of double-blind treatment. Subjects meeting the entry criteria for this study will be randomized to 
EN3835 treatment or placebo treatment in a 1:1 ratio within an investigational site.  
The complete Schedule of Events is provided in section 5. 
Figure 1: 
Study Design 
 
Table 3: 
Study Treatment Groups 
Dose per 
Each Injectiona / 
Number of 
Subjects 
Injection 
Volume per 
Each Injection 
Number of 
Injections at Each 
Treatment Visit 
Dose (mg) at Each 
Treatment Visit 
Injection Volume 
(mL) per Each 
Treatment Visit 
Cumulative  
EFP Dose 
EN3835 0.07 mg / 
N=210 
0.3 mL 
12 per buttock  
× 2 buttocks =  
24 injections 
0.84 mg per buttock  
× 2 buttocks = 
1.68 mg 
(12 injections  
per buttock ×  
0.07 mg/injection ×  
2 buttocks) 
3.6 mL per buttock  
× 2 buttocks = 
7.2 mL  
(24 injections × 
0.3 mL) 
5.04 mg 
(3 treatment visits × 
0.84 mg per buttock 
× 2 buttocks) 
Placebo /  
N=210 
0.3 mL 
12 per buttock  
× 2 buttocks =  
24 injections 
- 
3.6 mL per buttock  
× 2 buttocks = 
7.2 mL  
(24 injections × 
0.3 mL) 
- 
a Each injection of study drug is 0.3 mL administered as three 0.1 mL aliquots. 
10.2. 
Selection of Doses 
The dose of EN3835 chosen for this study was based on the results from earlier studies. 
The data from the Phase 2a EFP dose-ranging study (AUX-CC-831) suggest that EN3835 
0.84 mg is most effective in the treatment of EFP based on improvement in the severity of 

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cellulite as determined by both the Investigator and the subject, although the EN3835 0.48-mg 
group did show improvement in some of the efficacy parameters. 
• There were no safety concerns following administration of up to 3 treatment visits of 
EN3835 0.84 mg in the treatment of EFP (AUX-CC-831 CSR). The safety profile of 
EN3835 0.84 mg in the treatment of EFP was similar to that observed in the EN3835 
0.06-mg group and the EN3835 0.48-mg group. No notable differences were 
observed across the 3 treatment groups. 
• Safety findings from the Phase 2a EFP dose-ranging study are similar to that 
observed in previous clinical studies with XIAFLEX in the treatment of Dupuytren’s 
contracture and Peyronie’s disease, in that the majority of AEs occurred at the site of 
injection and resolved before the next scheduled treatment. 
• The immunogenicity profile of EN3835 in the Phase 2a EFP dose-ranging study is 
similar to that observed in the Dupuytren’s contracture and Peyronie’s disease 
programs. 
• Based on the efficacy and safety findings from the Phase 2a EFP dose-ranging study, 
the EN3835 0.84-mg dose was carried forward to the Phase 2b study. 
The results from the Phase 2b EFP study (EN3835-201) further suggested that EN3835 0.84 mg 
is an effective treatment of EFP based on improvement in the severity of cellulite as determined 
by the Investigator and the subject. There were no safety concerns following EN3835 0.84 mg 
in the treatment of EFP (section 8.4). Safety findings from the Phase 2b EFP study are similar to 
that observed in previous clinical studies with XIAFLEX in the treatment of Dupuytren’s 
contracture and Peyronie’s disease, in that that the majority of AEs occurred at the site of 
injection and resolved before the next scheduled treatment. The immunogenicity profile of 
EN3835 in the Phase 2b EFP study is similar to that observed in the Dupuytren’s contracture 
and Peyronie’s disease programs. 
Based on the efficacy and safety findings from the Phase 2a and 2b EFP studies, the EN3835 
0.84-mg dose per treatment area was carried forward to this study. The findings from previous 
studies that the majority of adverse events after EN3835 treatment are local to the injection site 
and that there is no quantifiable systemic exposure observed after concurrent treatment of two 
buttocks (total dose of 1.68 mg) supports the proposed study to evaluate EN3835 treatment of 
two buttocks. 
10.3. 
Study Drug Administration 
Study drug will be injected subcutaneously while the subject is in a prone position using a 
syringe with a 30-gauge ½-inch needle. Each injection site will receive a single skin injection of 
study drug administered as three 0.1-mL aliquots to Positions A, B, and C (for a total injection 
volume of 0.3 mL) as shown in the following figure. The depth of injection corresponds to the 
length of the treatment needle (0.5 inches) from the tip of the needle to the hub or base of the 
needle without downward pressure. 

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NOTE: EN3835 is a foreign protein and Investigators should be prepared to address and manage 
an allergic reaction should it occur. At the time of each injection, a 1:1,000 solution of 
epinephrine for injection, 50-mg diphenhydramine injection or a suitable equivalent, and oxygen 
must be available with the Investigator and site staff must be familiar with their use. 
10.4. 
Care Procedures After Injection 
To evaluate the subject for possible immediate immunological AEs, the subject will remain in 
direct observation of medical personnel who are skilled in the management of an allergic 
reaction for 30 minutes after receiving the injections of study drug and until the subject exhibits 
no sign of an immunological or other clinically significant systemic or local AE. The subject’s 
vital signs should be stable before the subject can leave direct observation (see section 14.9). 
The Investigator or qualified designee will then apply a sterile dressing to the injection areas 
with hypoallergenic tape. The subject will be instructed to remove the dressing in the evening. 
10.5. 
Discussion of Study Design, Including the Choice of Control Groups 
The design of this study was based on the primary objective to evaluate the efficacy and safety of 
EN3835 0.84 mg per buttock in the concurrent treatment (total dose of 1.68 mg) of 2 bilateral 
buttocks with EFP in adult women compared with placebo treatment. The study design, a 
multi-center, double-blind, placebo-controlled study is in accordance with regulatory guidelines 
of adequate and well-controlled clinical studies (Food and Drug Administration [FDA] Guidance 
for Industry: Providing Clinical Evidence of Effectiveness for Human Drug and Biological 
Products, 1998.; ICH E8 and E10). 
 

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11. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
11.1. 
Subject Inclusion Criteria 
In order to be eligible to participate in the study, subjects must meet the following criteria: 
1. Voluntarily sign and date an informed consent agreement 
2. Be a female ≥18 years of age 
3. At Screening visit, have 2 bilateral buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as reported by the Investigator (CR-PCSS) 
4. At Day 1 visit, have 2 bilateral buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as reported by the Investigator (CR-PCSS) 
5. Be willing to apply sunscreen to the buttocks before each exposure to the sun while 
participating in the study (ie, Screening through end of study) 
6. Be judged to be in good health, based upon the results of a medical history, physical 
examination, and laboratory profile at Screening 
7. Have a negative serum pregnancy test at Screening and a negative urine pregnancy test 
before injection of study drug and be using a stable and effective contraception method 
(eg, abstinence, intrauterine device [IUD], hormonal [estrogen/progestin] contraceptives, 
or double barrier method) for at least 1 menstrual cycle prior to study enrollment and for 
the duration of the study; or be menopausal defined as 12 months of amenorrhea in the 
absence of other biological or physiological causes, as determined by the Investigator; or 
post-menopausal for at least 1 year; or be surgically sterile 
8. Be willing and able to cooperate with the requirements of the study 
9. Be able to read, complete and understand the patient-reported outcomes rating 
instruments in English 
11.2. 
Subject Exclusion Criteria 
Subjects who meet any of the following criteria will not be eligible to participate in the study: 
1. Has any of the following systemic conditions: 
a. Coagulation disorder 
b. Evidence or history of malignancy (other than excised basal-cell carcinoma) unless 
there has been no recurrence in at least 5 years 
c. History of keloidal scarring or abnormal wound healing 
d. Concurrent diseases or conditions that might interfere with the conduct of the study, 
confound the interpretation of the study results, or endanger the subject’s well-being. 

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Any questions about concurrent diseases should be discussed with the Medical 
Monitor 
e. Evidence of clinically significant abnormalities on physical examination, vital signs, 
electrocardiogram (ECG), or clinical laboratory values 
2. Has any of the following local conditions in the areas to be treated: 
a. History of lower extremity thrombosis or post-thrombosis syndrome 
b. Vascular disorder (eg, varicose veins, telangiectasia) in area to be treated 
c. Inflammation or active infection 
d. Severe skin laxity, flaccidity, and/or sagging 
e. Active cutaneous alteration including rash, eczema, psoriasis, or skin cancer 
f. Has a tattoo and/or a mole located within 2 cm of the site of injection 
3. Requires the following concomitant medications before or during participation in the 
trial: 
a. Anticoagulant or antiplatelet medication or has received anticoagulant or antiplatelet 
medication (except for ≤150 mg aspirin daily) within 7 days before injection of study 
drug 
4. Has used any of the following for the treatment of EFP on a buttock within the timelines 
identified below or intends to use any of the following at any time during the course of 
the study: 
a. Liposuction in a buttock during the 12-month period before injection of study drug 
b. Injections (eg, mesotherapy); radiofrequency device treatments; laser treatment; 
buttock implant treatment; cryolipolysis; or surgery (including subcision and/or 
powered subcision) within a buttock during the 12-month period before injection of 
study drug 
c. Any investigational treatment for EFP on a buttock during the 12-month period 
before the injection of study drug 
d. Endermologie or similar treatments within a buttock during the 6-month period 
before injection of study drug 
e. Massage therapy within a buttock during the 3-month period before injection of study 
drug 
f. Creams (eg, Celluvera™, TriLastin®) and/or home therapies to prevent or mitigate 
EFP within a buttock during the 2-week period before injection of study drug 
5. Is presently nursing or providing breast milk  
6. Intends to become pregnant during the study 
7. Intends to initiate an intensive sport or exercise program during the study 
8. Intends to initiate a weight reduction program during the study 
9. Intends to use tanning spray or tanning booths during the study 

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10. Has received an investigational drug or treatment within 30 days before injection of study 
drug 
11. Has a known systemic allergy to collagenase or any other excipient of study drug 
12. Has received any collagenase treatments at any time prior to treatment 
13. Was a subject in a previous cellulite clinical trial of CCH: AUX-CC-830, AUX-CC-831, 
EN3835-102, EN3835-104, EN3835-201, EN3835-202, and/or EN3835-205 
14. Any other condition(s) that, in the Investigator’s opinion, might indicate the subject to be 
unsuitable for the study  
11.3. 
Subject Discontinuation Criteria 
A premature discontinuation will occur when a subject who signed informed consent ceases 
participation in the study, regardless of circumstances, prior to the completion of the protocol. 
Subjects can be prematurely discontinued from the study for one of the following reasons: 
• An adverse event 
• Lack of efficacy 
• A protocol violation (reason must be specified, for example: lack of compliance, use 
of a prohibited concomitant medication, failure to meet inclusion/exclusion criteria 
after study entry, etc.) 
• Withdrawal by subject (reason must be specified) 
• The subject was “lost to follow-up” 
• Other reasons (reason must be specified, for example: the subject moved, pregnancy, 
Investigator decision, Sponsor decision to terminate trial, etc.) 
If a subject discontinues from the study, all end-of-study procedures including safety and 
efficacy assessments should be conducted as detailed in the Schedule of Events (section 5). The 
date a subject discontinues and the reason for discontinuation will be recorded in the source 
documentation and electronic case report form (eCRF). If, however, a subject withdraws consent, 
no end-of-study procedures and assessments are required (but are encouraged to reduce missing 
information) except the collection of adverse event (AE) information. This information should be 
recorded in the source documentation and the eCRF. 
11.3.1. 
Replacement Procedures 
Subjects who discontinue from the study will not be replaced. 

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12. 
TREATMENT OF SUBJECTS 
12.1. 
Study Visits 
The Schedule of Events to be performed at each visit is shown in section 5. Provided below are 
further details where additional instruction about the assessments that will be performed is 
deemed to be needed. 
12.1.1. 
Informed Consent 
Signed and dated informed consent will be obtained from each subject before any study 
procedures are undertaken, or before any changes to the subject’s medication regimen are made. 
Details about how the informed consent will be obtained and documented are provided in 
section 21.3, Subject Information and Consent. 
12.1.2. 
Subject Screening 
Investigators will be expected to maintain a Screening log of all potential study subjects. This log 
will include limited information about the potential subject and the date and outcome of the 
screening process (eg, enrolled into the study, reason for ineligibility, or refused to participate). 
Investigators will provide information about the study to subjects who appear to meet the criteria 
for participation in the study. The screening log will be captured directly by the electronic data 
capture (EDC) system. 
12.1.2.1. Medical History 
During the screening period, the Investigator or qualified designee will obtain a medical history 
from each subject that includes relevant diagnoses and/or procedures/therapies with 
onset/resolutions dates. Medical histories should also include history of EFP (start date and 
family history), and history of tobacco and alcohol use (never, current, former). 
12.1.2.2. Screening Period (Day -14 to Day -1) 
Subjects meeting the relevant eligibility criteria listed in section 11 may be enrolled in the study 
after the nature and purpose of the protocol have been explained and written informed consent to 
participate has been voluntarily provided by the subject or their legally authorized representative. 
The subject identification number will consist of 8 digits. The first 4 digits represent the study 
site number followed by a 4-digit subject number. 
The following procedures will be performed and documented during the screening period: 
1. Obtain written informed consent (section 12.1.1) 
2. Evaluate eligibility based on inclusion/exclusion criteria (section 11.1 and section 11.2) 
3. Subject will have digital photographs taken of her two buttocks (section 13.1.1) 
4. Subjects will get instruction on the use of the PR-PCSS (section 13.1.2.1) 

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5. Prior to Investigator CR-PCSS assessment, subjects will rate each of their two buttocks 
using the PR-PCSS while viewing their digital images (section 13.1.2.1); the Investigator 
is blinded to these ratings 
6. After the subject has completed the PR-PCSS ratings, the Investigator will conduct live 
assessments of subject’s cellulite severity of each of the two buttocks using the CR-PCSS 
(section 13.1.2.6); the subject is blinded to these ratings. The ratings from the PR-PCSS 
and CR-PCSS will be used to assess initial eligibility of the buttocks for study entry 
7. Medical history including EFP history (section 12.1.2.1) 
8. Record prior and concomitant medications/procedures (section 12.8) 
9. Physical examination including measurement of body weight, height, Fitzpatrick skin 
type (section 14.11) 
10. Vital sign measurements (section 14.9) 
11. 12-lead ECG (section 14.10) 
12. Collection of samples for: 
a. Clinical laboratory testing (section 14.7) 
b. Serum pregnancy testing (section 14.7) 
13. Adverse events (section 14) 
12.2. 
Selecting and Marking Dimples during Treatment Visits 
Selection of dimples to be treated in the two buttocks is at the discretion of the Investigator. 
Dimples must be well-defined and evident when the subject is standing in a consistent, 
standardized relaxed pose (without the use of any manipulation such as skin pinching or muscle 
contraction). Each subject will receive 3 treatment visits of study drug according to 
randomization unless the buttock is dimple-free (score of 0 on CR-PCSS as reported by the 
Investigator) at Treatment Visit 2 and/or Treatment Visit 3 (a dimple -free buttock at Treatment 
Visit 1 is precluded by the eligibility criteria); a dimple-free buttock at Treatment Visit 2 and/or 
Treatment Visit 3 does not preclude treatment of the contralateral buttock unless it is dimple-free 
also. During each treatment visit, each of the buttocks will be photographed before and after 
marking dimples and injection sites while the subject is standing in a consistent, standardized 
relaxed pose as described in the Photography Manual. The cellulite severity assessments using 
the PR-PCSS and CR-PCSS will be completed prior to marking dimples and injection sites. 
The Investigator or qualified designee will select dimples within each buttock that are 
well-defined, evident when the subject is standing, and suitable for treatment; treatment consists 
of 12 injections per buttock (24 injections total in two buttocks) per treatment visit. Because the 
goal of treatment is to improve the aesthetic appearance of each entire buttock, the Investigator 
will be instructed to select dimples that in his or her opinion would most improve the aesthetic 
appearance of each entire buttock. The same dimples within a buttock or different dimples within 
a buttock may be treated at each treatment visit but injections must all be within the buttocks 
(12 injections per buttock) for all 3 visits. Each buttock will receive all 3 treatment visits unless 
the buttock has no treatable EFP dimples and the Investigator rates the buttock a score of 0 on 
the CR-PCSS. If no injections in a particular buttock (right or left) are given at Treatment 

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Visit 2, subjects will still be assessed for treatment in the contralateral buttock at Treatment 
Visit 2, and will return for the Day 43 visit and each of the buttocks will again be evaluated by 
the subject (PR-PCSS) and Investigator (CR-PCSS). If the Investigator rates either or both of the 
buttocks greater than 0 on the CR-PCSS, injections at Treatment Visit 3 should be given. 
For each dimple selected for treatment, the Investigator or qualified designee will choose 
injection sites (injection sites within a dimple should be spaced approximately 2 cm apart, if a 
dimple requires more than 1 injection; locating at least one injection site at the nadir, if present, 
of the dimple). Each injection site will be marked with a “dot” using a surgical marker. For 
round dimples, the “dot” will be placed in the center of the dimple; for elongated dimples, “dots” 
will be spaced out approximately 2 cm along the longer axis of the dimple. The Investigator or 
qualified designee will then use a surgical marker to circle each of the dimples selected for 
treatment. Circles in the buttock should not overlap. 
Each of the buttocks will be photographed before and after marking dimples and injection sites 
while the subject is standing in a consistent, standardized relaxed pose as described in the 
Photography Manual. 
Examples of subject dimple and injection site markings are shown as follows: 
Sample Buttock Marking 
 
12.3. 
Digital Photography during Treatment Visits 1, 2, and 3 
During each treatment visit, each of the two buttocks will be photographed before and after 
marking dimples and injections sites while the subject is standing in a consistent, standardized 
relaxed pose as described in section 13.1.1. 

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12.4. 
Treatment Visit 1 (Day 1) 
12.4.1. 
Treatment Visit 1: Pre-Injection 
1. Confirm eligibility criteria 
2. Take digital photography of each of the buttocks before marking dimples and injection 
sites (section 13.1.1) 
3. Subjects will get instruction on the use of the PR-PCSS (Patient Instructions for Use of 
PR-PCSS) 
4. Subjects will rate each of their buttocks using the PR-PCSS (section 13.1.2.1); the 
Investigator is blinded to these ratings 
5. Subjects will complete the Patient Reported Cellulite Impact Scale assessment (PR-CIS; 
section 13.1.2.3): the Investigator is blinded to this rating 
6. Subjects will complete the Subject Self-Rating Scale (SSRS) assessment 
(section 13.1.2.5); the Investigator is blinded to these ratings 
7. The Investigator will conduct live assessments of subject’s cellulite severity of each of 
the buttocks using the CR-PCSS (section 13.1.2.6); the subject is blinded to these ratings. 
The ratings from the PR-PCSS and CR-PCSS will be used to assess eligibility for 
randomization 
8. Subjects with PR-PCSS or CR-PCSS ratings in either of the buttocks <3 will be excluded 
from participation 
9. Upon confirmation of two buttocks eligible for treatment (eligible criteria being each 
buttock have PR-PCSS and CR-PCSS scores of 3 or 4), the IWRS system will randomly 
assign one buttock as the target buttock in the background. Subjects, investigators, site 
personnel and Endo personnel will be blinded to target buttock assignment. 
10. Randomization of subjects with two buttocks eligible for treatment (eligible criteria being 
each buttock have PR-PCSS and CR-PCSS scores of 3 or 4) to treatment (section 12.10); 
obtain kit numbers of study treatment. Subjects, investigators, site personnel, and Endo 
personnel will be blinded to treatment assignment. 
11. Record concomitant medications/procedures (section 12.8) 
12. Vital sign measurements (section 14.9) 
13. Collection of samples for: 
a. Anti-AUX-I and anti-AUX-II antibody testing (section 14.8) 
b. Urine pregnancy testing (section 14.7) 
14. Select and mark dimples to be treated in each of the buttocks (section 12.2) 
15. Take digital photograph of each of the buttocks after marking dimples and injection sites 
(section 13.1.1) 

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12.4.2. 
Treatment Visit 1: Injection and Post-injection 
1. Administration of study drug in the prone position (section 10.3) 
2. Record number of dimples treated and number of injections administered in each of the 
two buttocks 
3. Vital sign measurements (section 14.9) 
4. Injection site reactions and local tolerability 
5. Adverse events (section 14) 
12.5. 
Treatment Visit 2 (Day 22 [±3 days]) and Treatment Visit 3 (Day 43 
[±3 days]) 
12.5.1. 
Treatment Visits 2 and 3: Pre-injection 
1. Record concomitant medications/procedures (section 12.8) 
2. Body weight measurements 
3. Vital sign measurements (section 14.9) 
4. Collection of samples for: 
a. Anti-AUX-I and anti-AUX-II antibody testing (section 14.8) 
b. Urine pregnancy testing (section 14.7) 
5. Digital photographs of each of the two buttocks before marking dimples and injection 
sites (section 13.1.1) 
6. Subject Cellulite Assessments of each of the buttocks using the photographic image of 
each buttock before marking dimples and injection sites (NOTE: complete subject 
cellulite assessments before Investigator cellulite assessments) in the following sequential 
order using: 
a. Patient Reported Photonumeric Cellulite Severity Scale (PR-PCSS) assessment 
(section 13.1.2.1); complete this prior to conducting S-GAIS  
b. Subject Global Aesthetic Improvement Scale (S-GAIS) (section 13.1.2.2) 
7. Investigator Cellulite Assessments live of each of the buttocks in the following sequential 
order prior to marking dimples and injection sites using: 
a. Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) live assessment 
of subject (section 13.1.2.6) 
b. Investigator Global Aesthetic Improvement Scale (I-GAIS) (section 13.1.2.7) 
8. Select and mark dimples to be treated in each buttock (section 12.2) 
9. Digital photographs of each buttock after marking dimples and injection sites 
(section 13.1.1)  
10. For eligible buttock(s), obtain kit number(s) of study treatment 

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12.5.2. 
Treatment Visits 2 and 3: Injection and Post-injection 
1. Administration of study drug in the prone position (section 10.3) 
2. Record number of dimples treated and number of injections administered in each buttock 
3. Vital sign measurements (section 14.9) 
4. Injection site reactions and local tolerability 
5. Adverse events (section 14) 
12.6. 
Day 71 (+5 days) / End of Study / Early Termination 
The following procedures will be performed on Day 71: 
1. Record concomitant medications/procedures (section 12.8) 
2. Measurement of body weight 
3. Vital sign measurements (section 14.9) 
4. Collection of samples for: 
a. Clinical laboratory testing (section 14.7) 
b. Serum pregnancy test (section 14.7) 
c. Anti-AUX-I and anti-AUX-II antibody testing (section 14.8) 
5. Digital photographs of each of the buttocks 
6. Subject Cellulite Assessment of each of the two buttocks using the photographic image 
before marking dimples and injection sites (NOTE: complete subject cellulite 
assessments before Investigator cellulite assessments) using: 
a. Patient Reported Photonumeric Cellulite Severity Scale (PR-PCSS) assessment 
(section 13.1.2.1) 
b. Subject Global Aesthetic Improvement Scale (S-GAIS) (section 13.1.2.2) 
c. Patient Reported Cellulite Impact Scale (PR-CIS) assessment (section 13.1.2.3); note 
this assessment is of both left and right buttocks rather than each individual buttock 
d. Subject Satisfaction with Cellulite Treatment Assessment (section 13.1.2.4); note this 
assessment is of both left and right buttocks rather than each individual buttock 
e. Subject Self-Rating Scale (SSRS) assessment (section 13.1.2.5); note this assessment 
is of both left and right buttocks rather than each individual buttock 
7. Investigator Cellulite Assessments of each of the buttocks live using: 
a. Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) live assessment 
of subject (section 13.1.2.6) 
b. Investigator Global Aesthetic Improvement Scale (I-GAIS) (section 13.1.2.7) 
8. Injection site reactions and local tolerability 
9. Adverse events (section 14) 

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12.7. 
Unscheduled Visits 
If any subject needs to return to the site prior to her next scheduled visit, site staff should follow 
the Unscheduled Visit procedures outlined in section 5. Site staff may conduct additional study 
procedures if required. 
12.8. 
Prior and Concomitant Medications and Procedures 
All prior medications taken within 90 days before randomization will be recorded. All 
medications (including over-the-counter medications) taken by the subject on Day 1 through the 
end of the study must be recorded. Any prior treatments (medications or procedures) for EFP 
through the end of the study must be recorded on the appropriate eCRF page. 
Additionally, any diagnostic, therapeutic or surgical procedures performed during the study 
period should be recorded including the date, indication for and description of the procedure. 
12.8.1. 
Prohibited Medications or Procedures 
The following medications are prohibited for randomized subjects during the study: 
anticoagulants (warfarin, heparin, direct thrombin inhibitors, Factor X inhibitors) and antiplatelet 
agents (aspirin >150 mg/day and P2Y12 inhibitors, such as clopidogrel), which can cause 
additional bruising. However the use of aspirin at a dose level of ≤150 mg per day will be 
permitted during study. 
Procedures listed in exclusion criterion #4 (section 11.2, Exclusion Criterion #4) are prohibited 
for randomized subjects during the study. 
Table 4: 
Concomitant Medication Restrictions for Subjects during the Treatment 
Phase of Study 
Drug Class 
Restrictions 
Anticoagulants 
Subjects cannot take antiplatelet agents or anticoagulants (except for 
≤150 mg aspirin daily) within 7 days before and 7 days after the dosing 
administration. 
12.9. 
Treatment Compliance 
Randomized subjects will receive study drug administered by an Investigator at the 
Investigator’s site. 
Accidental or intentional overdoses should be reported to the Sponsor/designee promptly (see 
section 14.6.2.1, Overdose). 
12.10. 
Blinding and Randomization 
On Day 1, if each of the buttocks (ie, both buttocks) again meet the criteria (3 or 4 on the 
PR-PCSS and CR-PCSS), one buttock will be randomly assigned by the IWRS as the target 
buttock for the primary efficacy endpoint. Subjects, investigators, site personnel, and Endo 
personnel will be blinded to the identification of the target buttock.  

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On Day 1, if each of the buttocks (ie, both buttocks) again meet the criteria (3 or 4 on the 
PR-PCSS and CR-PCSS), the subject will be randomized to a treatment group. The interactive 
web response system (IWRS) will randomly assign each subject to a treatment group (EN3835 
0.84 mg per buttock × two buttocks or placebo) in a 1:1 ratio within an investigational site. The 
treatment group will remain blinded to the Investigator, subjects, all site personnel, and the 
sponsor. The IWRS will assign the subject study drug kit numbers associated with the 
randomized treatment. At Day 22 and 43 visits, the IWRS will again assign the subject study 
drug kit numbers associated with the randomized treatment assigned at Day 1.  
All precautions will be taken to ensure that the blinding of EN3835 and placebo is maintained 
throughout the study period. Unblinding will not be permitted by the study site unless it is 
deemed necessary for treatment of a medical emergency. Before breaking the blind, the 
Investigator should make every attempt to contact the Medical Monitor to discuss the necessity 
of breaking the blind. The study site will have the ability to immediately determine treatment 
identification in the event of an emergency by using the unblinding function within the IWRS, 
however, the Medical Monitor must be notified immediately. The Investigator will be required to 
make a full written explanation of the reason for unblinding the subject and the date. In the event 
that a subject is unblinded prior to contacting the Medical Monitor, the Investigator must provide 
this information in writing to the Medical Monitor as soon as possible. Breaking the blind at the 
investigative site will immediately disqualify the subject from further participation in the study. 
In addition, the event(s) leading to emergency unblinding must be reported as an SAE according 
to instructions in section 14.5.2, Reporting Serious Adverse Events. 
In addition, it may be necessary for the Investigator or qualified designee to unblind a subject as 
a result of a clinically significant finding noted during safety review by the Investigator, Safety 
Monitor, Medical Monitor and/or qualified designee that might jeopardize subject safety. 
 

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13. 
ASSESSMENT OF EFFICACY 
13.1. 
Efficacy Measurements 
13.1.1. 
Digital Photography  
Although digital photographs are not direct efficacy measurements, digital photography will be 
utilized in the assessment of certain efficacy measurements ie to assess certain cellulite severity 
parameters at specific intervals (see section 5, Schedule of Events). At the Screening visit, the 
Investigator or qualified designee will photograph each buttock using a Sponsor-supplied 
standardized digital camera in a standardized manner. The subject will be standing for each 
photography session and will be wearing a standardized photographic garment as described in 
the Photography Manual. The Investigator or qualified designee will photograph each of the two 
buttocks while the subject is standing in a consistent, standardized relaxed standing pose, 
ie, standing position with relaxed gluteus muscles, at the following time points: 
• Screening (no markings of dimples or injection site) - each of the two buttocks 
• Before and after marking dimples and injection sites (prior to injections) on Days 1, 
22, and 43 - each of the two buttocks 
• During the Day 71 visit (end of study/early termination) (no dimple or injection site 
markings) - each of the two buttocks 
All photographs from this study are the property of Endo and may be utilized for clinical 
development, scientific communication, marketing, regulatory purposes, and/or legal 
applications as required/desired by Endo. 
13.1.2. 
Subject and Investigator Cellulite Assessments 
Investigator cellulite assessments are independent of the subject assessments. Therefore, all 
subject cellulite assessments must be completed before the Investigator’s cellulite assessments 
are initiated. At each visit prior to the subject assessments being completed, subjects will watch 
an ePRO and scale tutorial video and instructions. The site will document subject review of the 
training (video and instructions) in source documentation. The subject assessments will be done 
using a subject-assigned password protected electronic patient reported outcome (ePRO) system 
and the Investigator and study site personnel will not have access to the subject’s assessments or 
password; the clinician assessment will be recorded in an investigator-assigned password 
protected system and the subject will not have access to the Investigator’s assessments or 
password. Subject assessments will be done alone with no study site personnel in the room. 
Investigators will be instructed not to verbalize their ratings while in the presence of the subject. 
13.1.2.1. Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) 
The PR-PCSS will be conducted for the purpose of assessing the severity of cellulite in the 
buttock. The scale is a 5-level photonumeric scale developed specifically for patients and used 
by the subject to assess the severity of their cellulite in the buttocks by viewing digital images of 
each of their buttocks captured by photography at the visit; the ratings range from 0 (None) to 
4 (Severe) with labels and descriptors to aid the subject in the assessments.  

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At Screening and at the beginning of their visits on Day 1, Day 22, Day 43, and Day 71, subjects 
will have digital photographs taken of each of their two buttocks. Subjects will be given 
instructions in the proper use (Patient Instructions for Use of PR-PCSS) of the PR-PCSS and 
then perform the PR-PCSS for each of the buttocks (Appendix B). While viewing the digital 
images of each of their buttocks on a standardized computer monitor and using PR-PCSS for 
buttock, subjects will be instructed to answer the following question for each buttock: Today, 
how would you rate the severity of your cellulite in the area displayed using the PR-PCSS? The 
subject will be given the following explanations: Please try to match the severity of your 
cellulite, as seen in this digital image, with one of the cellulite levels on the PR-PCSS. Please 
look at the image of your cellulite and the pictures, labels, and descriptions on the PR-PCSS 
carefully before selecting your answer. If you feel that your cellulite level is between 2 of the 
levels, please select the level that is closest to your image. If you feel that your cellulite is exactly 
halfway between two PR-PCSS levels of cellulite severity, please select the more severe 
response. 
The subject will enter their rating electronically into an ePRO system; the Investigator and other 
site personnel will be blinded to the rating entered by the subject. This variable will be entered 
directly into the EDC system, thus the electronic database will serve as the direct point of data 
capture and will serve as source for this variable. 
13.1.2.2. Subject Global Aesthetic Improvement Scale (S-GAIS) 
Subjects will complete the S-GAIS for each of the buttocks as described below at the Day 22, 
Day 43, and Day 71 study visits using the pre-treatment Day 1 digital image (Baseline) of each 
of the buttocks for comparison. 
All treated subjects will be instructed to answer the following question for each buttock:  
How would you rate the appearance of your treated cellulite after treatment? 
The S-GAIS assessment will occur after the subject has completed the PR-PCSS assessment to 
avoid introducing potential bias to the static PR-PCSS assessment. The subject will view each of 
their pre-treatment Day 1 digital images alongside their Day 22, Day 43 or Day 71/End of study 
visit digital images of each of their buttocks to aid in the assessment (Table 5). Subjects will 
provide a rating from those below that best represents their answer for each treated buttock. 
This variable will be entered directly into the EDC system, thus the electronic database will serve 
as the direct point of data capture and will serve as source for this variable. 

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Table 5: 
Subject Global Aesthetic Improvement Scale (S-GAIS) 
Rating 
Response Option 
Description 
+3 
Very much improved 
My treated cellulite looks very much better. 
+2 
Much improved 
My treated cellulite looks much better, but additional treatment 
would slightly improve the result. 
+1 
Improved 
My treated cellulite looks better, but additional treatment is 
necessary. 
0 
No change 
My treated cellulite looks essentially the same as it did 
originally. 
−1 
Worse 
My treated cellulite looks worse than it did originally. 
−2 
Much worse 
My treated cellulite looks much worse than it did originally. 
−3 
Very much worse 
My treated cellulite looks very much worse than it did 
originally. 
13.1.2.3. Patient Reported Cellulite Impact Scale (PR-CIS) 
At the Day 1 visit and the Day 71 visit, subjects will be instructed to answer 6 questions related 
to the areas selected for treatment on their buttocks on the PR-CIS (Appendix D) while viewing 
digital images of their buttocks. The PR-CIS assesses the visual and emotional impact of cellulite 
(happy, bothered, self-conscience, embarrassed, looking older, or looking overweight or out of 
shape) using a 6-question survey, with each question rated on a numerical rating scale from 
0 (not at all) to 10 (extremely). 
This variable will be entered directly into the EDC system, thus the electronic database will serve 
as the direct point of data capture and will serve as source for this variable. 
13.1.2.4. Subject Satisfaction with Cellulite Treatment Assessment 
At the Day 71 visit, subjects will be instructed to answer a question related to their treated 
buttocks while viewing digital images of their buttocks. Subjects will be given a list of responses 
and they will provide a rating from those below that best represents their answer (Table 6). 
Today, how satisfied are you with the results of the cellulite treatment you received on the 
specific area or areas on your buttocks that were treated? 
This variable will be entered directly into the EDC system, thus the electronic database will serve 
as the direct point of data capture and will serve as source for this variable. 
Table 6: 
Subject Satisfaction with Cellulite Treatment Assessment - Buttocks 
Rating 
Description 
+2 
I am very satisfied with the cellulite treatment on my buttocks. 
+1 
I am satisfied with the cellulite treatment on my buttocks. 
0 
I am neither dissatisfied nor satisfied with the cellulite treatment on my buttocks. 
-1 
I am dissatisfied with the cellulite treatment on my buttocks. 
-2 
I am very dissatisfied with the cellulite treatment on my buttocks. 

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13.1.2.5. Subject Self-Rating Scale (SSRS) 
The SSRS is a measure that assesses subject satisfaction with appearance in association with 
cellulite on the buttocks using whole numbers on a 7-level scale that ranges from 0 (extremely 
dissatisfied to 6 (extremely satisfied). The patient will be asked to respond to the question related 
to the satisfaction with appearance of the cellulite on their buttocks on the appropriate visit day 
(note Day 71 question is different than Day 1 question). No photographs or reference to previous 
ratings or evaluations will be used. Subjects will be given a list of responses and they will 
provide a rating from those below that best represents their answer (Table 7); the list of 
responses is the same for Day 1 and for Day 71. 
On Day 1 (Baseline), subjects will be instructed to answer: Considering your appearance in 
association with your cellulite on your buttocks, how satisfied do you feel with your appearance 
at the present time? 
On Day 71, subjects will be instructed to answer: Considering your appearance in association 
with your cellulite on your buttocks, how satisfied do you feel with your appearance at the 
present time whether or not in your judgment it is due entirely to treatment with EN3835? 
This variable will be entered directly into the EDC system, thus the electronic database will serve 
as the direct point of data capture and will serve as source for this variable. 
Table 7: 
Subject Self-Rating Scale (SSRS) 
Rating 
Response Option 
6 
Extremely satisfied 
5 
Satisfied 
4 
Slightly satisfied 
3 
Neither satisfied nor dissatisfied 
2 
Slightly dissatisfied 
1 
Dissatisfied 
0 
Extremely dissatisfied 
13.1.2.6. Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 
The CR-PCSS will be conducted for the purpose of assessing the severity of cellulite in the 
buttock. The scale is a 5-level photonumeric scale developed specifically for clinicians and used 
by the Investigator to assess the severity of the subject’s cellulite in each buttock by live 
assessments; the ratings range from 0 (None) to 4 (Severe) with labels and descriptors to aid the 
Investigator in the assessments. 
Investigators will be trained and qualified on the use of the CR-PCSS prior to assessing any 
subjects. 
At the Screening visit, the Investigator will determine severity of cellulite of each of the 
two buttocks via live assessment of the subject using the CR-PCSS for buttock (Appendix C) 
after the subject has completed her self-assessment using the PR-PCSS. Before injections on 
treatment visits Day 1, Day 22, and Day 43, and on visit Day 71; Investigators will evaluate each 
of the two buttocks by live assessments using the CR-PCSS for the buttock to make his/her 

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evaluation. At each visit, the Investigator will make his/her assessment independently and after 
the subject has conducted her self-assessment using the PR-PCSS. 
This variable will be entered directly into the EDC system, thus the electronic database will serve 
as the direct point of data capture and will serve as source for this variable. 
13.1.2.7. Investigator Global Aesthetic Improvement Scale (I-GAIS) 
Investigators will be trained by Endo or their designee on the use of the I-GAIS prior to 
assessing any subjects. At each visit, the Investigator may review the training and use material 
for the I-GAIS. On the Day 22, Day 43, and Day 71 study visits, the Investigator will determine 
the degree of improvement of each buttock by comparing the cellulite from the Day 1 
pre-treatment (Baseline) digital image of each buttock to the cellulite seen in a live assessment 
(Table 8). The I-GAIS assessment will occur after the CR-PCSS assessment (section 13.1.2.6) to 
avoid introducing potential bias to the static CR-PCSS assessment by the Investigator. For each 
buttock, the Investigator will provide the rating from those below that best represents his/her 
answer. 
This variable will be entered directly into the EDC system, thus the electronic database will serve 
as the direct point of data capture and will serve as source for this variable. 
Table 8: 
Investigator Global Aesthetic Improvement Scale (I-GAIS) 
Rating 
Response Option 
Description 
+3 
Very much improved 
Optimal cosmetic result from treatment of the treated dimples 
+2 
Much improved 
Marked improvement in the treated area appearance from 
before treatment, but not completely optimal 
+1 
Improved 
Obvious improvement in the treated area appearance from 
before treatment, but additional treatment is indicated 
0 
No change 
The treated area appearance is essentially the same as before 
treatment 
−1 
Worse 
The treated area appearance is worse than before treatment 
−2 
Much worse 
Marked worsening in appearance from the initial condition 
−3 
Very much worse 
Obvious worsening in appearance from the initial condition 

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14. 
ASSESSMENT OF SAFETY 
14.1. 
Definitions 
14.1.1. 
Adverse Events 
An adverse event (AE) is any unfavorable or unintended change in body structure (signs), body 
function (symptoms), laboratory result (eg, chemistry, ECG, X-ray, etc.), or worsening of a 
pre-existing condition associated temporally with the use of the study medication whether or not 
considered related to the study medication. Adverse events will be captured once a subject has 
signed the informed consent. AEs include: 
• Changes in the general condition of the subject 
• Subjective symptoms offered by or elicited from the subject 
• Objective signs observed by the Investigator or other study personnel 
• All concurrent diseases that occur after the start of the study, including any change in 
severity or frequency of pre-existing disease 
• All clinically relevant laboratory abnormalities or physical findings that occur during 
the study 
A treatment-emergent adverse event (TEAE) is any condition that was not present prior to 
treatment with study medication but appeared following treatment, was present at treatment 
initiation but worsened during treatment, or was present at treatment initiation but resolved and 
then reappeared while the individual was on treatment (regardless of the intensity of the AE 
when the treatment was initiated). 
All AEs, including both observed or volunteered problems, complaints, signs or symptoms must 
be recorded on the AE page of the eCRF, regardless of whether associated with the use of study 
medication. This would include AEs resulting from concurrent illness, reactions to concurrent 
medication use, or progression of disease states (excluding the disease under study). A condition 
present at baseline that worsens after initiation of study treatment will be captured as an AE; the 
onset date will be the date the event worsened. The AE should be recorded in standard medical 
terminology when possible. 
14.1.2. 
Serious Adverse Events 
A serious adverse event (SAE) is defined as an AE that: 
• Results in death 
• Is immediately life-threatening (there is an immediate risk of death from the AE as it 
occurred; this does not include an AE that had it occurred in a more serious form may 
have caused death) 
• Results in or prolongs an inpatient hospitalization (Note: a hospitalization for elective 
or pre-planned surgery, procedure, or drug therapy does not constitute an SAE) 

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• Results in permanent or substantial disability (permanent or substantial disruption of 
one’s ability to conduct normal life functions) 
• Is a congenital anomaly/birth defect (in offspring of a subject using the study 
medication regardless of time to diagnosis) 
• Is considered an important medical event 
Important medical events are defined as events that, based upon appropriate medical judgment, 
may jeopardize the subject and may require medical or surgical intervention to prevent one of the 
other serious outcomes. Examples of important medical events include malignancy, allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias 
or convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
14.2. 
Monitoring Adverse Events 
At each visit, subjects will be queried regarding any AEs that have occurred since the last visit. 
Subjects will be asked to volunteer information concerning AEs with a non-leading question 
such as, “How do you feel?” Study site personnel will then record all pertinent information in the 
source documents and the eCRF. The study drug compliance record should also be reviewed to 
detect potential overdoses (intentional/unintentional). 
14.3. 
Relationship to Study Drug 
The degree of “relatedness” of the AE to the study medication must be described using the 
following scale: 
• Not related indicates that the AE is definitely not related to the study medication. 
• Unlikely related indicates that there are other, more likely causes and study 
medication is not suspected as a cause. 
• Possibly related indicates that a direct cause and effect relationship between study 
medication and the AE has not been demonstrated, but there is evidence to suggest 
there is a reasonable possibility that the event was caused by the study medication. 
• Probably related indicates that there is evidence suggesting a direct cause and effect 
relationship between the AE and the study medication. 
It is the Sponsor’s policy to consider “Probably related” and “Possibly related” causality 
assessments as positive causality. “Not related” and “Unlikely related” causality assessments are 
considered as negative causality. 
Assessments will be recorded on the eCRF and must indicate clearly the relationship being 
assessed. For example, an AE that appears during a placebo run-in phase would be assessed with 
respect to the placebo treatment received and/or study procedures conducted during this phase. If 
the AE continued into an active treatment phase, the relationship would be assessed for the active 
treatment phase only if the AE worsened. 

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14.4. 
Intensity Assessment 
The intensity (or severity) of AEs is characterized as mild, moderate, or severe: 
• Mild AEs are usually transient, requiring no special treatment, and do not interfere 
with the subject’s daily activities. 
• Moderate AEs introduce a low level of inconvenience or concern to the subject and 
may interfere with daily activities, but are usually ameliorated by simple therapeutic 
measures. 
• Severe AEs interrupt a subject’s usual daily activity and typically require systemic 
drug therapy or other treatment. 
When the intensity category of an AE changes, the greatest intensity during that continuous 
episode should be recorded. 
14.5. 
Reporting Adverse Events and Serious Adverse Events 
14.5.1. 
Reporting Adverse Events 
Throughout the study, AEs will be documented on the source document and on the appropriate 
page of the eCRF whether or not considered treatment-related. This includes any new signs, 
symptoms, injury or illness, including increased severity of previously existing signs, symptoms, 
injury, or illness. Conditions existing prior to screening will be recorded as part of the subject’s 
medical history. The Investigator is responsible for assessing the relationship of AEs to the study 
medication; relationship will be classified as not related, unlikely related, possibly related, or 
probably related. 
All AEs will be collected by the Investigator from the time of signing the informed consent 
through 28 days after the last dose of study medication; this includes any AEs that are ongoing at 
the time of completion/termination of the study. All ongoing AEs must be followed until 
resolution or for 30 days after the subject’s last study visit, whichever comes first. 
14.5.2. 
Reporting Serious Adverse Events 
Any SAE, including death resulting from any cause, which occurs to any subject participating in 
this study must be reported via email or fax by the Investigator using the Endo Clinical Trial 
Report Form for SAEs within 24 hours of first becoming aware of the SAE. SAEs will be 
collected by the Investigator from the time of signing the informed consent through 28 days after 
the last dose of study medication. SAEs that occur within 28 days, following cessation of the 
study treatment, or within 30 days, following premature discontinuation from the study for any 
reason, must also be reported within the same timeframe. Any SAE that is felt by the Investigator 
to be related to the study medication must be reported regardless of the amount of time since the 
last dose received. Follow-up information collected for any initial report of an SAE must also be 
reported to the Sponsor within 24 hours of receipt by the Investigator. 
All SAEs will be followed until resolution, stabilization of condition, or until follow-up is no 
longer possible. 

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In the event discussion is necessary regarding treatment of a subject, call the Medical 
Monitor (see contact information in section 3). 
All SAEs should be sent via the email address, or faxed to the fax number, provided in 
section 3. 
The Sponsor will determine whether the SAE must be reported within 7 or 15 days to regulatory 
authorities in compliance with local and regional law. If so, the Sponsor (or the Sponsor’s 
representative) will report the event to the appropriate regulatory authorities. The Investigator 
will report SAEs to the IRB per their IRB policy. 
14.5.2.1. Follow-up Procedures for Serious Adverse Events 
To fully understand the nature of any SAE, obtaining follow-up information is important. 
Whenever possible, relevant medical records such as discharge summaries, medical 
consultations, and the like should be obtained. In the event of death, regardless of cause, all 
attempts should be made to obtain the death certificate and any autopsy report. These records 
should be reviewed in detail, and the Investigator should comment on any event, lab 
abnormality, or any other finding, noting whether it should be considered a serious or 
non-serious AE, or whether it should be considered as part of the subject’s history. In addition, 
all events or other findings determined to be SAEs should be identified on the follow-up SAE 
form and the Investigator should consider whether the event is related or not related to study 
drug. 
14.6. 
Special Reporting Situations 
14.6.1. 
Adverse Events of Special Interest 
Adverse events such as bruising, ecchymosis, hematomas, and contusions that occur remote to 
the site of drug administration, or any hypersensitivity reactions, including anaphylaxis, will be 
recorded and evaluated for seriousness and severity (see section 14.1.1, Adverse Events or 
section 14.1.2, Serious Adverse Events). 
In addition, local AEs associated with the injection site, including bruising, pain, nodules/mass, 
ulceration, erythema, pruritus, swelling, and/or induration, will be recorded and evaluated for 
seriousness and severity (see as appropriate, section 14.1.1, Adverse Events or section 14.1.2, 
Serious Adverse Events) 
14.6.2. 
Overdose/Misuse/Abuse 
14.6.2.1. Overdose 
Study drug overdose is any accidental or intentional use of study drug in an amount higher than 
the dose indicated by the protocol for that subject. Study drug compliance (see section 12.9) 
should be reviewed to detect potential instances of overdose (intentional or accidental). 
Any study drug overdose during the study should be noted on the study medication eCRF. 
An overdose is not an AE per se, however all AEs associated with an overdose should both be 
entered on the Adverse Event eCRF and reported using the procedures detailed in section 14.5.2, 
Reporting of Serious Adverse Events, even if the events do not meet seriousness criteria. If the 

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AE associated with an overdose does not meet seriousness criteria, it must still be reported using 
the Endo Clinical Trial Report Form for SAEs and in an expedited manner, but should be noted 
as non-serious on the form and the Adverse Event eCRF. 
14.6.3. 
Pregnancy 
Subjects should be instructed to immediately notify the Investigator of any pregnancies. 
Any pregnancy that occurs in a subject during this clinical study will be reported for tracking 
purposes only. All subject pregnancies that are identified during or after this study, where the 
estimated date of conception is determined to have occurred during study drug therapy or within 
28 days of the last dose of study medication need to be reported, followed to conclusion, and the 
outcome reported, even if the subject is discontinued from the study. The Investigator should 
report all pregnancies within 24 hours using the Initial Pregnancy Report Form, and any 
pregnancy-associated SAE using the SAE report form, according to the usual timelines and 
directions for SAE reporting provided in section 14.5.2. Monitoring of the pregnancy should 
continue until conclusion of the pregnancy; 1 or more Follow-up Pregnancy Report Form(s) 
detailing progress, and a Two Month Follow-up Pregnancy Report Form detailing the outcome, 
should be submitted. 
Pregnancy itself is not regarded as an AE unless there is suspicion that the investigational 
product under study may have interfered with the effectiveness of a contraceptive medication. 
Likewise, elective abortions without complications are not considered AEs. Any SAEs 
associated with pregnancy (eg, congenital abnormalities/birth defects/spontaneous miscarriages 
or any other serious events) must additionally be reported as such using the SAE report form. 
Spontaneous miscarriages should also be reported and handled as SAEs. 
A subject who becomes pregnant must be withdrawn from the study. Attempts to obtain the 
pregnancy follow-up and pregnancy outcome information detailed above are necessary even if a 
subject discontinues treatment because of pregnancy. 
14.6.4. 
AEs/SAEs Experienced by Non-subjects Exposed to Study Medication 
Non-subjects are persons who are not enrolled in the study but have been exposed to study 
medication, including instances of diversion of study medication. All such AEs/SAEs occurring 
in non-subjects from such exposure will be reported to the Endo PVRM Department (when the 
non-subject agrees) on the departmental form for serious adverse experiences regardless of 
whether the event is serious or not. Instructions for completing the form for events experienced 
by non-subjects will be provided. SAEs occurring in non-subjects exposed to study medication 
will be processed within the same SAE reporting timelines as described in section 14.5.2, 
Reporting Serious Adverse Events. Additionally, the drug accountability source documentation 
at the site should reflect this occurrence. 
14.7. 
Clinical Laboratory Determinations 
Clinical laboratory tests will be conducted according to the Schedule of Events (section 5). 
Clinical laboratory tests will be performed by a designated central laboratory. Each site will be 
provided with instructions on specimen collection, preparation, packaging and transport. Refer to 
the central laboratory manual for further information regarding sample collection, handling, and 
labeling. The results of the tests will be returned to the investigational sites.  

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Clinical laboratory test data will be reviewed by the Investigator, or designee, and additional 
clinical laboratory tests may be ordered at his/her discretion (eg, if the results of any clinical 
laboratory test falls outside the reference range or clinical symptoms necessitate additional 
testing to ensure safety). Any additional testing will be performed by the designated central 
laboratory. The Investigator or qualified designee must acknowledge the review of laboratory 
results. 
The Investigator will review all abnormal lab results for potentially clinically important. Any 
abnormal clinical laboratory test result meeting the Investigator’s criteria for potentially 
clinically important (refer to central laboratory manual) will be recorded as an AE or SAE as 
appropriate (see section 14.1.1, Adverse Events, and section 14.1.2, Serious Adverse Events). 
Laboratory results will be sent electronically to Endo Pharmaceuticals Inc. for data management. 
Clinical laboratory parameters that will be measured in this study are listed in Table 9. 
Table 9: 
Clinical Laboratory Tests 
Hematology 
Biochemistry 
Urinalysis 
Hemoglobin 
Hematocrit 
Red blood cell 
White blood cell (WBC) 
Platelets 
WBC Differential 
Glucose 
Sodium 
Potassium 
Calcium 
Chloride 
CO2 
Inorganic phosphate 
Blood urea nitrogen  
Creatinine 
Creatinine clearance (estimated)  
Aspartate transaminase (AST) 
Alanine transaminase (ALT) 
Gamma-glutamyl transferase (GGT) 
Total bilirubin (TBL) (direct bilirubin reflex if elevated) 
Albumin 
Alkaline phosphatase (ALP) 
Uric acid 
Glucose 
Protein 
Specific gravity 
pH 
Ketones 
Bilirubin 
Urobilinogen 
Nitrite 
Blood* 
Leukocytes* 
* Microscopic examination will be performed if blood or leukocytes are detected by dipstick. 
For women of childbearing potential, a serum pregnancy test will be performed at Screening and 
Day 71/End of Study/Early Termination, and urine pregnancy tests will be performed at Day 1, 
Day 22, and Day 43 (refer to section 5). Female subjects of childbearing potential must have a 
negative pregnancy test at the Screening Visit and at Day 1 (Baseline), Day 22, and Day 43 to be 
randomized and/or receive treatment in the study. If necessary, additional urine pregnancy tests 
can be performed at any time during the study at the discretion of the Investigator. Urine 
pregnancy test kits will be supplied by the Sponsor. 

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14.11. 
Physical Examination 
A complete physical examination will be performed at the Screening Visit. All examinations will 
be performed by a physician or health professional listed on the Form FDA 1572 and licensed to 
perform physical examinations. Height and body weight will be measured and recorded at 
screening. 
The Investigator will review all physical exam findings for clinical significance. Any physical 
exam finding meeting the Investigator’s or Sponsor’s criteria for clinical significance will be 
recorded as an AE or SAE as appropriate (see section 14.1.1, Adverse Events and section 14.1.2, 
Serious Adverse Events). 
At screening, the Investigator will also assess the subject’s skin type using the Fitzpatrick scale 
(Table 11). Only the Fitzpatrick Scale shown below may be used during the study. 
Table 11: 
Fitzpatrick Scale 
I 
Pale white skin, blue/hazel eyes, blond/red hair 
Always burns, does not tan 
II 
Fair skin, blue eyes 
Burns easily, tans poorly 
III 
Darker white skin 
Tans after initial burn 
IV 
Light brown skin 
Burns minimally, tans easily 
V 
Brown skin 
Rarely burns, tans darkly easily 
VI 
Dark brown or black skin 
Never burns, always tans darkly 
Follow-up body weight will be measured before injection on Day 22 and Day 43 and at the 
Day 71 visit. 
14.12. 
Other Safety Assessments 
Not applicable. 

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15. 
ASSESSMENT OF PHARMACOKINETICS 
Not applicable. 

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16. 
ASSESSMENT OF PHARMACODYNAMICS 
Not applicable. 

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17.2. 
Subject Populations 
Four (4) populations are considered in the statistical analysis of the study: safety, intent-to-treat 
(ITT), modified ITT (mITT), and per-protocol (PP). 
17.2.1. 
Safety Population 
The safety population is defined as all enrolled subjects who have received at least one injection 
of study medication. All safety parameters will be summarized based on this population. 
17.2.2. 
Intent-to-Treat (ITT) Population 
The ITT population is defined as all randomized subjects who have received at least one 
injection of study medication. All demographic and baseline characteristic summaries will be 
based on this population. The primary and key secondary efficacy parameters will be 
summarized based on this population. 
17.2.3. 
Modified Intent-to-Treat (mITT) Population 
The mITT population is defined as all intent-to-treat subjects with a baseline and at least 1 
post-injection evaluation of both the Investigator CR-PCSS and subject PR-PCSS for both the 
target and non-target buttocks. All secondary and supportive efficacy evaluations will be based 
on the mITT population. 
17.2.4. 
Per-Protocol (PP) Population 
The PP population is defined as the mITT subjects without any of the following :  
• Placebo randomized subject who receives EN3835 treatment. 
• EN3835 randomized subject who receives placebo treatment only throughout study. 
• Any subject who uses protocol-prohibited medications. 
• Subject missing PR-PCSS and/or CR-PCSS assessment at Day 71. 
• Subject with a buttock not receiving all three treatment sessions without medical 
reasons (e.g., adverse events or CR-PCSS rated as zero (0)). 
• Subject who did not meet all inclusion and exclusion criteria.  
This population may be used in the efficacy sensitivity analysis. 
17.3. 
Subject Disposition 
The number of subjects included in each study population will be summarized by treatment 
group. Subjects excluded from the safety and efficacy (eg, ITT) populations will be listed by 
treatment group. 
The number and percentage of subjects completed and prematurely discontinued during the 
treatment period will be presented for each treatment group and pooled across treatment groups. 
Screen failures (ie, screened but not randomized subjects) and the associated failure reasons will 
be tabulated overall. Reasons for premature discontinuation from the treatment period as 
recorded on the termination page of the eCRF will be summarized (number and percentage) by 

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treatment group for all randomized subjects. Percentage of premature discontinuations will be 
compared between treatment groups. 
17.4. 
Demographics and Other Baseline Characteristics 
The summarization of demographic variables (eg, age, sex, race, weight, height, and body mass 
index [BMI]), medical and surgical history, and other baseline characteristics relevant to the 
indication studied in the study will be described. 
Demographic characteristics, including sex, age, age group, race, height, and weight, will be 
summarized by treatment group, for the ITT population, using descriptive statistics. All 
screening characteristics and medical information will also be summarized by treatment group 
using descriptive statistics. The descriptive summaries will include frequency tables for all 
categorical response variables and n, mean, standard deviation (SD), median, minimum, and 
maximum for all continuous variables. 
17.5. 
Efficacy Analyses 
All efficacy endpoints including supportive efficacy analysis will be summarized as percentages. 
The dichotomous secondary endpoints (ie, responder endpoints) will be analyzed using a 
Cochran-Mantel-Haenszel test adjusted for Investigator. Changes in the PR-PCSS ratings and 
CR-PCSS ratings from baselines, S-GAIS scores, I-GAIS scores, and SSRS scores will be 
analyzed using the Wilcoxon rank sum test. Changes in PR-CIS from baselines will be analyzed 
using an analysis of covariance (ANCOVA) adjusted for baseline values. All the tests are two-
sided. 
The primary endpoint will be summarized as percentages and analyzed using a Cochran-Mantel-
Haenszel test that compares the 2 treatment groups and adjusts for Investigator at a level of 
significance of 0.05 based on the ITT population. Any subject who does not have an evaluation 
of CR-PCSS and/or PR-PCSS at Day 71 will be classified as a non-responder. 
The key secondary efficacy analyses will be analyzed in the same manner as the primary 
endpoint based on the ITT population. Any subject who does not have an evaluation at Day 71 
will be classified as a non-responder for the analyses. The family #1 key secondary efficacy 
analyses will be performed only if the primary efficacy analysis is significant (p ≤ 0.05; 
gatekeeping strategy). Similarly family #2 key secondary efficacy analyses will be performed 
only if at least one of the key secondary efficacy endpoints of family #1 is significant  
(p ≤ 0.0125; parallel gatekeeping strategy) and family #3 key secondary efficacy analyses will be 
performed only if at least one of the key secondary efficacy endpoints of family #2 is significant 
(parallel gatekeeping strategy). Within a family of key secondary efficacy endpoints, the 
Bonferroni method will be performed to relocate unused alpha for testing each endpoint to assure 
an overall error rate of p ≤ 0.05. The details of the testing procedures will be provided in the 
statistical analysis plan for the study. 
All supportive endpoints will be summarized as subject counts and percentages for categorical 
data or n, mean, SD, median, minimum, and maximum for continuous data. All the supportive 
analyses will be performed based on all observed data (ie, missing data not imputed) in the mITT 
population at all visits without multiplicity adjustment. This analysis will also be performed at 
Day 71 with missing data at Day 71 imputed by a last observation carried forward (LOCF) 

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approach if subjects have at least one post-dose assessment. The dichotomous secondary 
endpoints (ie, responder endpoints) will be analyzed using a Cochran-Mantel-Haenszel test 
adjusted for Investigator. Changes in the PR-PCSS ratings and CR-PCSS ratings from baselines, 
S-GAIS scores, I-GAIS scores, and SSRS scores will be analyzed using the Wilcoxon rank sum 
test. Changes in PR-CIS from baselines will be analyzed using an analysis of covariance 
(ANCOVA) adjusted for baseline values. 
17.5.1. 
Primary Efficacy Variable 
The primary efficacy variable is the proportion of 2-level composite responders at Day 71 
defined as subjects with: 
• an improvement in severity from baseline (Day 1 visit) of at least 2 levels of severity 
in the CR-PCSS as assessed live by the Investigator of the target buttock, and  
• an improvement in severity from baseline of at least 2 levels of severity in the 
PR-PCSS by the subject while viewing the digital image of the target buttock. 
A subject will be considered a responder if these criteria are met in the randomized target buttock 
of that subject.  
Sensitivity analyses for the primary endpoint will include: 
• ITT subjects with missing data handled by multiple imputation (MI) approach 
• ITT subjects with missing data handled by an LOCF approach 
• mITT subjects with missing data handled by an LOCF approach 
• Observed data only (no missing data handling) 
• Per-protocol (PP) subjects with missing data handled by an LOCF approach if 10% or 
more subjects are excluded in the PP population from mITT population 
17.5.2. 
Secondary Efficacy Variables 
17.5.2.1. Key Secondary Variables 
There will be 8 key secondary endpoints grouped in three families of 2 to 4 endpoints per family 
analyzed in hierarchical order. 
• Family #1 – four endpoints: 
− Proportion of 1-level PR-PCSS responders defined as subjects with ≥1-level 
improvement in PR-PCSS severity rating of the target buttock at Day 71 
compared to Day 1 
− Proportion of 2-level PR-PCSS responders defined as subjects with ≥2-level 
improvement in PR-PCSS severity rating of the target buttock at Day 71 
compared to Day 1 
− Proportion of 1-level composite responders of the target buttock (defined as 
subjects with an improvement in severity from baseline of at least 1 level of 
severity in the CR-PCSS of the target buttock assessed live by the Investigator 

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and an improvement of severity from baseline of at least 1 level of severity in the 
PR-PCSS of the target buttock) at Day 71 compared to Day 1 
− Proportion of 2-level composite responders of the non-target buttock at Day 71 
compared to Day 1 
• Family #2 – two endpoints: 
− Proportion of 1-level SSRS responders defined as subjects who were at least 
slightly satisfied at Day 71 (SSRS rating ≥ 4) 
− Change from baseline (Day 1) of the PR-CIS total score at Day 71 
• Family #3 – two endpoints: 
− Proportion of 1-level S-GAIS responders defined as subjects with ≥1-level 
improvement (improved, much improved or very much improved) in the S-GAIS 
assessment of the target buttock at Day 71 
− Proportion of 2-level S-GAIS responders defined as subjects with ≥2-level 
improvement (much improved or very much improved) in the S-GAIS assessment 
of the target buttock at Day 71 
Sensitivity analyses for the key secondary endpoints will include: 
• ITT subjects with missing data handled by MI approach 
• ITT subjects with missing data handled by an LOCF approach 
• mITT subjects with missing data handled by an LOCF approach 
• Observed data only (no missing data handling) 
• Per-protocol (PP) subjects with missing data handled by an LOCF approach if 10% or 
more subjects are excluded in the PP population from mITT population 
17.5.3. 
Supportive Efficacy Variables 
17.5.3.1. Supportive Variables 
The supportive variables will evaluate assessments at various study time points and using various 
populations. 
• Proportion of 2-level PR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 2 levels of severity in the PR-PCSS of the target 
buttock (Days 22, 43, and 71) 
• Proportion of 2-level PR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 2 levels of severity in the PR-PCSS of the 
non-target buttock (Days 22, 43, and 71) 
• Proportion of 1-level PR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 1 level of severity in the PR-PCSS of the target 
buttock (Days 22, 43, and 71) 

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• Proportion of 1-level PR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 1 level of severity in the PR-PCSS of the 
non-target buttock (Days 22, 43, and 71) 
• Proportion of 2-level PR-PCSS responders of at least one buttock (Days 22, 43, and 
71). A subject will be considered a responder if this criterion is met in the target 
buttock or non-target buttock or both buttocks in that subject. 
• Proportion of 1-level PR-PCSS responders of at least one buttock (Days 22, 43, and 
71). A subject will be considered a responder if this criterion is met in the target 
buttock or non-target buttock or both buttocks in that subject.  
• Proportion of 2-level PR-PCSS responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both the target and non-target buttocks. 
• Proportion of 1-level PR-PCSS responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both the target and non-target buttocks. 
• Proportion of 2-level CR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 2 levels of severity in the CR-PCSS of the target 
buttock (Days 22, 43, and 71) 
• Proportion of 2-level CR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 2 levels of severity in the CR-PCSS of the 
non-target buttock (Days 22, 43, and 71) 
• Proportion of 1-level CR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 1 level of severity in the CR-PCSS of the target 
buttock (Days 22, 43, and 71) 
• Proportion of 1-level CR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 1 level of severity in the CR-PCSS of the 
non-target buttock (Days 22, 43, and 71) 
• Proportion of 2-level CR-PCSS responders of at least one buttock (Days 22, 43, and 
71). A subject will be considered a responder if this criterion is met in the target 
buttock or non-target buttock or both buttocks in that subject. 
• Proportion of 1-level CR-PCSS responders of at least one buttock (Days 22, 43, and 
71). A subject will be considered a responder if this criterion is met in the target 
buttock or non-target buttock or both buttocks in that subject. 
• Proportion of 2-level CR-PCSS responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both the target and non-target buttocks. 
• Proportion of 1-level CR-PCSS responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both the target and non-target buttocks. 

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• Proportion of 1-level composite responders of the target buttock (defined as subjects 
with an improvement in severity from baseline of at least 1 level of severity in the 
CR-PCSS of the target buttock assessed live by the Investigator and an improvement 
of severity from baseline of at least 1 level of severity in the PR-PCSS of that same 
target buttock) (Days 22, 43, and 71) 
• Proportion of 1-level composite responders of the non-target buttock (defined as 
subjects with an improvement in severity from baseline of at least 1 level of severity 
in the CR-PCSS of the non-target buttock assessed live by the Investigator and an 
improvement of severity from baseline of at least 1 level of severity in the PR-PCSS 
of that same non-target buttock) (Days 22, 43, and 71) 
• Proportion of 1-level composite responders of at least one buttock (Days 22, 43, and 
71). A subject will be considered a responder if this criterion is met in the target 
buttock or non-target buttock or both buttocks in that subject. 
• Proportion of 1-level composite responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both the target and non-target buttocks. 
• Proportion of 2-level composite responders of the target buttock (defined as subjects 
with an improvement in severity from baseline of at least 2 levels of severity in the 
CR-PCSS of the target buttock assessed live by the Investigator and an improvement 
of severity from baseline of at least 2 levels of severity in the PR-PCSS of that same 
target buttock) (Days 22, 43, and 71) 
• Proportion of 2-level composite responders of the non-target buttock (defined as 
subjects with an improvement in severity from baseline of at least 2 levels of severity 
in the CR-PCSS of the non-target buttock assessed live by the Investigator and an 
improvement of severity from baseline of at least 2 levels of severity in the PR-PCSS 
of that same non-target buttock) (Days 22, 43, and 71) 
• Proportion of 2-level composite responders of at least one of two buttocks (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in the 
target buttock or non-target buttock or both buttocks in that subject.  
• Proportion of 2-level composite responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both the target and non-target buttocks. 
• Proportion of subjects at each level of the S-GAIS of the target buttock (Days 22, 43, 
and 71) 
• Proportion of subjects at each level of the S-GAIS of the non-target buttock (Days 22, 
43, and 71) 
• Proportion of 1-level S-GAIS responders defined as subjects with a response of at 
least 1 (improved) in the S-GAIS of the target buttock (Days 22, 43, and 71) 
• Proportion of 1-level S-GAIS responders defined as subjects with a response of at 
least 1 (improved) in the S-GAIS of the non-target buttock (Days 22, 43, and 71) 

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• Proportion 1-level S-GAIS responders of at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if this criterion is met in the target buttock or 
non-target buttock or both buttocks in that subject. 
• Proportion of 1-level S-GAIS responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both the target and non-target right buttocks. 
• Proportion of subjects at each level of the I-GAIS of the target buttock (Days 22, 43, 
and 71) 
• Proportion of subjects at each level of the I-GAIS of the non-target buttock (Days 22, 
43, and 71) 
• Proportion of 1-level I-GAIS responders defined as subjects with a response of at 
least 1 (improved) in the I-GAIS of the target buttock (Days 22, 43, and 71). 
• Proportion of 1-level I-GAIS responders defined as subjects with a response of at 
least 1 (improved) in the I-GAIS of the non-target buttock (Days 22, 43, and 71). 
• Proportion of 1-level I-GAIS responders of at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if this criterion is met in the target buttock or 
non-target buttock or both buttocks in that subject.  
• Proportion of 1-level I-GAIS responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both the target and non-target buttocks. 
• Change from baseline (Day 1) of the PR-CIS total score at Day 71 
• Change from baseline (Day 1) of the abbreviated PR-CIS score at Day 71 
• Proportion of subjects with a change from baseline (Day 1) of the PR-CIS ≥ 12 at 
Day 71 
• Proportion of subjects with a change from baseline (Day 1) of the abbreviated 
PR-CIS ≥ 10 at Day 71 
• Proportion of subjects at each level of the SSRS (Day 1 (Baseline) and Day 71) 
• Proportion of 1-level SSRS responders defined as subjects who were at least slightly 
satisfied at Day 71 (SSRS rating ≥ 4) 
• Proportion of subjects at each level of the subject satisfaction with cellulite treatment 
assessment (Day 71) 
• Proportion of satisfied responders (defined as subjects with a response of at least 1 
(ie, 1-Satisfied or 2-Very Satisfied) in the subject satisfaction with cellulite treatment 
assessment (Day 71) 

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17.6. 
Safety Analyses 
Safety variables include adverse events, laboratory parameters, vital signs, ECG parameters, and 
physical examinations. For each safety parameter, the last assessment made prior to the first dose 
of study drug will be used as the baseline for all analyses of that safety parameter. 
17.6.1. 
Prior, Concomitant, and Follow-up Medication 
The World Health Organization (WHO) Drug Dictionary will be used to classify prior and 
concomitant medications by therapeutic class. Prior medication will be defined as any 
medication taken prior to the first dose of study drug. Concomitant medication is defined as any 
medication taken on or after the date of first dose of study drug. 
Prior and concomitant medication use will be summarized descriptively by the number and 
percentage of subjects for each preferred term (generic name from WHO dictionary) by 
treatment. Multiple use of the same medication by a subject will be counted only once. 
17.6.2. 
Study Drug Exposure 
The following information regarding treatment will be summarized per each treated buttock by 
treatment group: 
• Total number of treatment visits 
• Number of subjects who had treatment session done or treatment session not done at 
each treatment visit 
• For subjects who had the treatment session done, the number of subjects who got all 
24 injections at the treatment visit or who received less than 24 injections 
• Number of injections given at each treatment visit  
• Number of dimples treated at each treatment visit  
• Average number of injections per dimple at each treatment visit  
Subjects who did not receive all 3 treatment visits and who did not receive 24 injections at a 
treatment visit will be listed. 
17.6.3. 
Measurement of Treatment Compliance 
Not applicable (the study drug is administered at the site by the study investigator). 
17.6.4. 
Adverse Events 
The Medical Dictionary for Regulatory Activities (MedDRA) will be used to code AEs. 
An AE (classified by preferred term) that started on or after the date of the first dose of the study 
drug will be considered a TEAE if it was not present prior to the first dose of study drug, or was 
present prior to the first dose of study drug but increased in intensity during the treatment period. 
If more than 1 AE is reported prior to the first dose of study drug and coded to the same 
preferred term, then the AE with the greatest intensity will be used as the benchmark for 
comparison to the AEs occurring during the treatment period which were also coded to that 
preferred term. Any AE present prior to the first dose of study drug that increases in intensity 

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during the treatment period will be re-entered with a new start date of the date of increased 
intensity. 
Descriptive statistics (the number and percentage) for subjects reporting TEAEs in each 
treatment group will be tabulated by system organ class and preferred term; by system organ 
class, preferred term, and severity; and by system organ class, preferred term, and relationship to 
study drug. If more than 1 AE is coded to the same preferred term for the same subject, the 
subject will be counted only once for that preferred term using the most severe and most related 
occurrence for the summarization by severity and by relationship to the study drug. 
The by-frequency summaries will also include incidence of the SAEs and non-SAEs by preferred 
term that at least 2% of the subjects in one treatment group. Duration of AEs will be tabulated by 
treatment group. 
The Fisher exact test will be used to compare EN3835 to placebo. 
Listings will be presented for subjects with SAEs, subjects with AEs leading to discontinuation 
of study or study drug, and subjects who die (if any). 
17.6.5. 
Vital Signs 
Descriptive statistics for vital signs (eg, systolic and diastolic blood pressure, pulse rate, and 
body weight) and their changes from baseline at each visit and at the end of study will be 
presented by treatment group. 
Vital sign values are potentially clinically important (PCI) if they meet both the observed value 
criteria and the change from baseline criteria. The criteria for PCI vital sign values will be 
detailed in the Statistical Analysis Plan (SAP). The PCI percentages will be calculated relative to 
the number of subjects with baseline and at least one post-baseline assessment. A supportive 
listing of subject values will be provided including the subject ID, study center, treatment group, 
baseline and post-baseline values. 
The change from baseline for vital signs parameters are compared between EN3835 and placebo 
using an analysis of variance (ANOVA) with a factor of drug (EN3835 or placebo) while the 
Fisher exact test will be used for the incidence of PCI values. 
17.6.6. 
Clinical Laboratory Parameters 
Descriptive statistics for clinical laboratory values in International System of Units (SI units) and 
changes from baseline at Day 71 will be presented by treatment group for each clinical 
laboratory parameter. 
The number and percentage of subjects with potentially clinically important (PCI) post-baseline 
clinical laboratory values will be tabulated by treatment group. The criteria for PCI laboratory 
values will be detailed in the Statistical Analysis Plan (SAP). The PCI percentages will be 
calculated relative to the number of subjects with at least one post-baseline assessment. A 
supportive listing of subjects with post-baseline PCI values will be provided, including the 
subject ID, study center, treatment group, baseline and post-baseline values. 
The change from baseline for clinical laboratory parameters are compared between EN3835 and 
placebo using an ANOVA with a factor of drug (EN3835 or placebo) while the Fisher exact test 
will be used for the incidence of PCI values. 

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18.5. 
Study Drug Accountability 
A drug inventory form must be kept current by the site staff designated to be responsible for 
reconstitution and must be made available to the clinical monitor, Endo employees, IRB/IEC, 
and regulatory agencies for routine inspection and accountability during monitoring visits. When 
instructed by Endo, the Investigator agrees to return all original used or unused study drug kits to 
Endo's return vendor. 
18.5.1. 
Study Drug Handling and Disposal 
The Investigator agrees not to supply study drug to any person except to those subjects enrolled 
in the study. The Investigator is responsible for recording the receipt and use of all drugs 
supplied and for ensuring the supervision of the storage and allocation of these supplies. All used 
and unused study drug will be returned, and unit counts will be performed whenever medication 
is returned. The site must account for all study drug received and its use. At the end of the study, 
all used and unused drug supplies will be returned to Endo’s return vendor. 
 

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19. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
19.1. 
Source Documents 
Source documents include but are not limited to original documents, data and records such as 
hospital/medical records (including electronic health records), clinic charts, lab results, subject 
diaries, data recorded in automated instruments, microfilm or magnetic media, and pharmacy 
records, etc. This study allows for direct data entry (DDE) for selected data points as outlined 
below: 
• PR-PCSS 
• CR-PCSS 
• S-GAIS 
• I-GAIS 
• PR-CIS 
• Subject Satisfaction with Cellulite Treatment Assessment 
• SSRS 
All other data points, at a minimum, should have supporting source documentation for entries in 
the eCRF. 
19.2. 
Study Monitoring 
A representative of Endo Pharmaceuticals Inc. will meet with the Investigator and his/her staff 
prior to the entrance of the first subject to review study procedures and methods of recording 
findings in the eCRF. 
After enrollment of the first subject, an Endo Pharmaceuticals Inc. representative will be 
assigned to periodically monitor each Investigator site for study progress and to verify that 
standards of Good Clinical Practice (GCP) were followed. The Investigator is expected to 
prepare for the monitor visit, ensuring that all source documents, completed eCRFs, signed 
consent forms and other study related documents are readily available for review. 
19.3. 
Audits and Inspections 
The Investigator shall permit audits and inspections by the Sponsor, its representatives and 
members of regulatory agencies. The Investigator should immediately notify the Sponsor of an 
upcoming FDA or other regulatory agency inspection. 
19.4. 
Institutional Review Board (IRB) 
The Investigator shall permit members of the IRB/IEC to have direct access to source 
documents. 

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19.5. 
Data Recording and Documentation 
All data recordings and source documentation (including electronic health records) must be made 
available to the Sponsor (or designee), FDA and any other regulatory agencies that request 
access to study records, including source documents, for inspection and copying, in keeping with 
federal and local regulations. 
 

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20. 
QUALITY CONTROL AND QUALITY ASSURANCE 
Steps to assure the accuracy and reliability of data include the selection of qualified principal 
investigators and appropriate study centers, review of protocol procedures with the principal 
investigators and associated personnel prior to start of the study, and periodic monitoring visits 
conducted by the Sponsor or Sponsor representative. Significant and/or repeated non-compliance 
will be investigated and remedial action instituted when appropriate. Failure to comply with 
remedial actions may result in investigator site termination and regulatory authority notification. 
The Sponsor or its designee will utilize qualified monitors to review and evaluate activities 
conducted at Investigator Sites. 
The data will be entered into the clinical study database and verified for accuracy, following 
procedures defined by the Sponsor (or designee). Data will be processed and analyzed following 
procedures defined by the Sponsor (or designee). 
The study will be monitored and/or audited at intervals to ensure that the clinical study is 
conducted and data are generated, documented (recorded), and reported in compliance with the 
Study Protocol; International Conference on Harmonisation (ICH), E6 consolidated guidelines; 
and other applicable regulations. The extent, nature, and frequency of monitoring and/or audits 
will be based on such considerations as the study objectives and/or endpoints, the purpose of the 
study, study design complexity, and enrollment rate. At the conclusion of a program, a 
compliance statement will be generated by the Sponsor (or designee) listing all audit activities 
performed during the clinical study. 
 

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21. 
ETHICS 
21.1. 
Ethics Review 
Approval by the IRB/IEC prior to the start of the study will be the responsibility of the 
Investigator. A copy of approval documentation will be supplied to Endo Pharmaceuticals Inc. 
along with a roster of IRB members that demonstrates appropriate composition (a Department of 
Health and Human Services [DHHS] Assurance Number will satisfy this requirement). 
The study protocol, the informed consent form, advertisements, materials being provided to 
subjects and amendments (if any) will be approved to IRB/IECs at each study center in 
conformance with ICH E6, the Code of Federal Regulations (CFR), Title 21, Part 56 and any 
other applicable local laws. The Investigator is responsible for supplying the IRB/IEC with a 
copy of the current IB, Package Insert, or SPC as well as any updates issued during the study. 
During the course of the study, the Investigator will provide timely and accurate reports to the 
IRB/IEC on the progress of the study, at intervals not exceeding 1 year (or as appropriate), and 
will notify the IRB/IEC of SAEs or other significant safety findings, per the policy of the 
IRB/IEC. At the conclusion of the study, the Investigator will submit a final report or close out 
report to the IRB/IEC and provide a copy to Endo Pharmaceuticals Inc. 
Any amendment to this protocol will be provided to the Investigator in writing by Endo 
Pharmaceuticals Inc. No protocol amendment may be implemented (with the exceptions noted 
below) before it has been approved by the IRB and the signature page, signed by the 
Investigator, has been received by Endo Pharmaceuticals Inc. Where the protocol is amended to 
eliminate or reduce the risk to the subject, the amendment may be implemented before IRB 
review and approval. However, the IRB must be informed in writing of such an amendment and 
approval obtained within reasonable time limits. Deviating from the protocol is permitted only if 
absolutely necessary for the safety or clinical management of the subject, and must be 
immediately reported to Endo Pharmaceuticals Inc. 
The Investigator will be responsible for supplying updated safety and/or study information to 
study subjects as it becomes available. 
21.2. 
Ethical Conduct of the Study 
This clinical study is designed to comply with the ICH Guidance on General Considerations for 
Clinical Trials (62 FR 6611, December 17, 1997), Nonclinical Safety Studies for the Conduct of 
Human Clinical Trials for Pharmaceuticals (62 FR 62922, November 25, 1997), Good Clinical 
Practice: Consolidated Guidance (62 FR 25692, May 9, 1997) and 21 CFR parts 50, 54, 56 
and 312. 
The study will be conducted in full compliance with ICH E6, the FDA guidelines for GCP and in 
accordance with the ethical principles that have their origins in the Declaration of Helsinki 
defined in 21 CFR, 312.120. 

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21.3. 
Subject Information and Consent 
Subjects, after having the study explained to them and an opportunity to have their questions 
answered sufficiently, will give voluntary and written informed consent (in compliance with ICH 
E6, 4.8 and 21 CFR Parts 50 and 312) before participating in any study-related procedures. The 
consent shall be written in a language understandable to the subject. Subjects unable to read 
(illiterate) shall have the consent process performed in the presence of an independent witness 
who shall also sign the consent. Each subject will read, assent understanding, and sign an 
instrument of informed consent after having had an opportunity to discuss the study and consent 
documents with the Investigator before signing, and will be made aware that she may withdraw 
from the study at any time. 
In addition to obtaining informed consent/assent, the Investigator is responsible for obtaining any 
additional documentation to demonstrate compliance with local privacy laws applicable to 
activities performed. 
The consent/assent process shall be recorded in source documents. Signed copies of the informed 
consent and/or assent will be given to the Subject/LAR and originals will be placed in the 
Investigator study files. 
A unique Subject identification number will be assigned according to section 12.1.2.2 at the time 
that the Subject signs the informed consent form. 
 

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22. 
DATA HANDLING AND RECORDKEEPING 
22.1. 
Data Collection 
Endo will provide an electronic data capture (EDC) system for this study. Data collection will 
involve the use of an EDC system to which only authorized personnel will have access. The 
system will be secured to prevent unauthorized access to the data or the system. This will include 
the requirement for a user ID and password to enter or change data. The level of access to the 
EDC system will be dependent on the person’s role in the study. 
Study data will be collected from source documents and entered into an eCRF within the EDC 
system. The Investigator will be responsible for ensuring the eCRFs are completed in a timely 
manner relative to the subject’s visit. In addition to periodic monitoring occurring within the 
system by a Sponsor monitor, programmatic edit checks will be used to review EDC data for 
completeness, logic, and adherence to the study protocol. As a result of this monitoring and these 
checks, queries may be issued electronically to the clinical study sites and closed electronically 
by the monitor, data management staff or authorized staff at the study site. Additionally, the 
Investigator will review eCRFs, ensure all missing or corrected data is provided and will sign the 
eCRF pages with an electronic signature. 
An electronic audit trail will be maintained in the EDC system to track all changes made to data 
entered in the eCRF. Data will be retrievable in such a fashion that all information regarding 
each individual subject is attributable to that subject. Unless otherwise indicated, all data 
captured in the eCRF must first be captured in source documents. Data that can be directly 
recorded in the eCRF will be clearly identified in the section(s) of the protocol that describes the 
assessment(s). 
Data entries will be corrected by changing the entry in the EDC system. Any changes or 
corrections to eCRF data will be electronically tracked and will include the reason for correction, 
who made the correction and the date/time stamp when the correction was made within the audit 
trail of the EDC system. 
In addition, any contact with the subject via telephone or other means that provide significant 
clinical information must be documented in source documents as described above. 
22.2. 
Study Documentation 
Upon study completion, the Investigator will be provided with complete electronic copies of the 
case report form (CRF) data for his/her files. 

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23. 
REPORTING AND PUBLICATION 
All data generated in this study are the property of Endo Pharmaceuticals Inc. An integrated 
clinical and statistical report will be prepared at the completion of the study. 
Publication of the results by the Investigator will be subject to mutual agreement between the 
Investigator and Endo Pharmaceuticals Inc. 
 

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24. 
INVESTIGATOR OBLIGATIONS 
24.1. 
Regulatory Documents 
The Investigator is responsible for creating and/or maintaining all study documentation required 
by 21CFR 50, 54, 56 and 312, ICH, E6 section 8, as well as any other documentation defined in 
the protocol or the Investigator Agreement. The Investigator must maintain the documentation 
relating to this study and permit Endo Pharmaceuticals Inc. or a member of a regulatory agency 
access to such records. 
The Investigator must provide the following key documents to Endo Pharmaceuticals Inc. prior 
to the start of the study: 
• A completed and signed Form FDA 1572. If during the course of the study any 
information reported on the Form FDA 1572 changes, a revised Form FDA 1572 
must be completed and returned to Endo Pharmaceuticals Inc. for submission to the 
FDA. For studies executed outside the United States, documentation required by the 
governing regulatory authority may be substituted for the Form FDA 1572. 
• A fully executed contract 
• The Investigator’s Statement page in this protocol signed and dated by the 
Investigator and any subsequent amendment signature pages 
• The IB acknowledgment of receipt page 
• Curricula vitae for the Principal Investigator and all sub-Investigators listed on Form 
FDA 1572, including a copy of each physician’s license (if applicable) 
• A copy of the original IRB/IEC approval for conducting the study. If the study is 
ongoing, renewals must be submitted at yearly intervals or shorter intervals defined 
by the IRB/IEC. All subsequent modifications must be submitted and approved by the 
IRB, as described in section 21.1 
• A copy of the IRB/IEC-approved informed consent form 
• A list of IRB/IEC members or DHHS Assurance Number 
• Laboratory certifications and normal ranges (if local labs are required by the protocol) 
• A financial disclosure agreement completed and signed by the Investigator and all 
sub-Investigators listed on Form FDA 1572. Investigator site staff that submitted an 
initial financial disclosure are also responsible for informing Endo Pharmaceuticals 
Inc. of any changes to their initial financial disclosure form 1 year after the 
completion of the study 
A complete list of required regulatory documents will be supplied by Endo Pharmaceuticals Inc. 
or its representative. 

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24.2. 
Delegation of Responsibilities and Adequate Resources 
The Investigator should have adequate time to conduct the study properly and should have an 
adequate number of qualified staff to assist with the conduct of the study. The Investigator shall 
delegate tasks only to individuals qualified by education, training and experience to perform the 
delegated tasks. The Investigator shall have direct oversight of all delegated activities and shall 
document delegation of responsibilities. The Investigator is responsible for ensuring all delegated 
staff have been properly trained on the protocol and their assigned study responsibilities. 
24.3. 
Medical Care of Study Subjects 
The Investigator and/or a qualified sub-Investigator shall be responsible for the subjects’ medical 
care. Any unrelated medical condition discovered during the course of the study should be 
communicated to the subject so that they may seek appropriate medical care. The Investigator 
will report all AEs as required by the protocol (section 14.5). The Investigator will inform study 
subjects of new information regarding the study drug as it becomes available. 
24.4. 
Use of Investigational Materials 
The Investigator will acknowledge that the study drug supplies are investigational and as such 
must be used strictly in accordance with the protocol and only under the supervision of the 
Principal Investigator or sub-Investigators listed on Form FDA 1572 (or other regulatory 
document, depending on region). Study drug must be stored in a safe and secure location. At 
study initiation, a representative from Endo Pharmaceuticals Inc. will inventory the study drug at 
the site. The Investigator must maintain adequate records documenting the receipt and 
disposition of all study supplies. Endo Pharmaceuticals Inc. or its representative will supply 
forms to document total inventory as well as subject specific accountability. The Investigator is 
responsible for monitoring subject’s use of the study drug to ensure compliance with the 
protocol. All study supplies shall be returned to Endo Pharmaceuticals Inc. or its designee. 
24.5. 
Retention of Records 
Federal and local regulations require that the Investigator retain a copy of all regulatory 
documents and records that support the data for this study (eg, informed consents, laboratory 
reports, source documents, study drug dispensing records) for whichever of the following is the 
longest period of time: 
• A period of 2 years following the final date of approval by the FDA or other 
regulatory agency of the study drug for the purposes that were the subject of the 
investigation; or 
• A period of 5 years following the date on which the results of the investigation were 
submitted to the FDA or other regulatory agency in support of, or as part of, an 
application for a research or marketing permit for the study drug for the purposes that 
were the subject of the investigation 
Endo Pharmaceuticals Inc. will notify Investigators once one of the above 2 timeframes has been 
satisfied. 

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If the investigation does not result in the submission of the data in support of, or as part of, an 
application for a research or marketing permit, records must be retained for a period of 2 years 
following notification by Endo Pharmaceuticals Inc. that the entire clinical investigation (not 
merely the Investigator’s portion) is completed, terminated, or discontinued or 2 years following 
withdrawal of the Investigational New Drug application (IND)/Clinical Trial Authorization 
(CTA) or request for marketing approval (New Drew Application [NDA]/Marketing 
Authorization Application [MAA]). 
If the Investigator retires, relocates, or for other reasons withdraws from the responsibility of 
keeping the study records, custody must be transferred to a person who will accept the 
responsibility. Endo Pharmaceuticals Inc. must be notified in writing of the name and address of 
the new custodian. Study records should not be destroyed without consultation with Endo 
Pharmaceuticals Inc. 
24.6. 
Subject Confidentiality 
All subject records submitted to Endo Pharmaceuticals Inc. or its designee will be identified only 
by initials and subject number. Subjects’ names are not to be transmitted to Endo 
Pharmaceuticals Inc. The Investigator will keep a Master Subject List on which the identification 
number and the full name, address, and telephone number of each subject are listed. It is the 
Investigators’ responsibility to inform study subjects that representatives of the Sponsor, FDA, or 
other regulatory agencies may review all records that support their participation in the study. The 
Investigator will adhere to all privacy laws to which he/she is subject. 
 

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25. 
TERMINATION OF STUDY 
The Sponsor has the right to suspend or terminate the study at any time. The study may be 
suspended or terminated for any reason. 
 

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26. 
INVESTIGATOR’S STATEMENT 
I agree to conduct the study in accordance with the protocol, and with all applicable government 
regulations and Good Clinical Practice guidance. 
 
 
 
_____/_____/______ 
Investigator’s Signature 
Date 
 
 
 
Typed Name of Investigator 
 

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27. 
REFERENCES 
1. Khan MH, Victor F, Rao B, Sadick NS. Treatment of cellulite: Part I. Pathophysiology. 
J Am Acad Dermatol 2010;62(3):361-70. 
2. Hexsel D, de Oliveira Dal’Forno T, Mazzuco R. Definition, clinical aspects, 
classifications, and diagnostic techniques. In: Goldman MP, Hexsel D, eds. Cellulite: 
Pathophysiology and Treatment. 2nd ed. New York, NY: Informa Healthcare; 
2010:13-21. 
3. Rawlings AV. Cellulite and its treatment. Int J Cosmetic Sci. 2006;28(3):175-90. 
4. Terranova F, Berardesca E, Maibach H. Cellulite: nature and aetiopathogenesis. Int J 
Cosmetic Sci. 2006;28(3):157-67. 
5. Avram MM. Cellulite: a review of its physiology and treatment. J Cosmet Laser Ther. 
2004;6(4):181-5. 
6. Khan MH, Victor F, Rao B, Sadick NS. Treatment of cellulite: Part II. Advances and 
controversies. J Am Acad Dermatol 2010;62(3):373-84. 
7. Collis N, Elliot LA, Sharpe C, Sharpe DT. Cellulite treatment: a myth or reality: a 
prospective randomized, controlled trial of two therapies, endermologie and 
aminophylline cream. Plast Reconstr Surg. 1999;104(4):1110-4. 
8. Hexsel DM, Mazzuco R. Subcision: a treatment for cellulite. Int J Dermatol. 
2000;39(7):539-44. 
9. Boyce S, Pabby A, Chuchaltkaren P, Brazzini B, Goldman MP. Clinical evaluation of a 
device for the treatment of cellulite: Triactive. Am J Cosmet Surg. 2005;22:233-7. 
10. DiBernardo BE. Treatment of cellulite using a 1440-nm pulsed laser with one-year 
follow-up. Aesthet Surg J. 2011;31(3):328-41. 
11. Investigational Brochure: Collagenase Clostridium Histolyticum for Injection 
(AA4500/EN3835), Version 8.0. Endo Pharmaceuticals Inc.; July 2017. 
 

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APPENDIX A. DOCUMENTS REQUIRED PRIOR TO INITIATION OF 
THE STUDY 
As a sponsor of a clinical study, Endo Pharmaceuticals Inc. has an obligation to ensure that the 
study will be conducted by a qualified Investigator with sufficient resources of time, personnel, 
and physical facilities to conduct the study and to ensure that the Investigator understands and 
agrees to comply with the protocol, applicable regulations, policies, and procedures. The 
following documentation is required: 
From the Principal Investigator 
1. A signed agreement to perform the study per protocol (the signature page will suffice). 
2. A signed Letter of Financial Agreement (including confidentiality statement). 
3. Name(s) of the Principal Investigator and of all sub-Investigator(s) 
4. All address(es) of the clinical site(s). 
5. A current medical license valid where he/she practices and a current curriculum vitae for 
the Principal Investigator (signed and dated) and all sub-Investigators, to contain at least 
the following elements: 
a. For physicians: 
i. Date of degree in Medicine 
ii. Name of the Institution granting the degree in Medicine 
iii. Previous clinical postings with dates 
b. For non-physician allowed by national law or regulations to act as clinical 
Investigators: 
i. Date and description of most advanced degree 
ii. Name of the Institution granting the degree in number (i) 
iii. Other accreditation or qualifications relevant to the study 
iv. Previous postings with dates 
v. Name and qualification (see 5a above) of the physician or dentist in charge of 
study subjects 
Note: If a non-physician is serving as Principal Investigator, then a qualified physician 
must be assigned as a sub-Investigator for the trial, to be responsible for all trial-related 
medical decisions. 
6. Written notification of Institutional Review Board/Independent Ethics Committee/Human 
Research Ethics Committee (IRB/IEC/HREC) approval. The minimum requirements are 
as follows: 
a. Dated letter, including: 
i. The date on which the meeting for the review of the study protocol took place 
ii. Study protocol/amendment number, and version date 

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iii. A clear statement of approval of the protocol and the informed consent text with 
version date, and authorization for the study to proceed 
iv. If the Investigator or any sub-Investigator is a part of the IRB/IEC/HREC 
Review Board, assurance that the Investigator abstained from voting at the 
meeting(s) when the study was discussed. 
b. A dated list of the members and their occupations 
c. A specimen copy of the Committee-approved informed consent text to be used in the 
study 
7. Food and Drug Administration (FDA) Form 1572 (for studies submitted under a US 
Investigational New Drug application [IND]). 
8. Financial Disclosure Certification or Certification of Non-Disclosure (for studies to be 
submitted for a US New Drug Application/Biologics License Application [NDA/BLA]). 
Other 
Any other documentation required by national law or regulations to be in the possession of the 
sponsor or the Investigator for study participation or study initiation. 

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APPENDIX B. PATIENT-REPORTED PHOTONUMERIC CELLULITE SEVERITY SCALE (PR-PCSS) 
FOR THE BUTTOCK 
 
 

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APPENDIX C. CLINICIAN-REPORTED PHOTONUMERIC CELLULITE SEVERITY SCALE 
(CR-PCSS) FOR THE BUTTOCK 
 

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APPENDIX D. PATIENT REPORTED CELLULITE IMPACT SCALE 
(PR-CIS) 
Please select the rating that best represents your answer on a scale of 0 to 10 with 0 representing 
“Not at all” and 10 representing “Extremely” while viewing digital images of your buttocks. 
Please answer each question. 
1. Thinking about the areas selected for treatment, how happy are you with the appearance of 
your cellulite? 
Not at all 
 
 
 
 
 
 
 
 
 
Extremely 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
2. Thinking about the areas selected for treatment, how bothered are you by the appearance of 
your cellulite? 
Not at all 
 
 
 
 
 
 
 
 
 
Extremely 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
3. Thinking about the areas selected for treatment, how self-conscious are you about the 
appearance of your cellulite? 
Not at all 
 
 
 
 
 
 
 
 
 
Extremely 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
4. Thinking about the areas selected for treatment, how embarrassed are you about the 
appearance of your cellulite? 
Not at all 
 
 
 
 
 
 
 
 
 
Extremely 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
5. Thinking about the areas selected for treatment, how much older do you look because of your 
cellulite? 
Not at all 
 
 
 
 
 
 
 
 
 
Extremely 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
6. Thinking about the areas selected for treatment, how overweight or out of shape do you look 
because of your cellulite? 
Not at all 
 
 
 
 
 
 
 
 
 
Extremely 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 

Protocol 
 
Endo Pharmaceuticals Inc. 
1400 Atwater Drive 
Malvern, PA 19355 USA 
EN3835 
EN3835-303 
A PHASE 3, RANDOMIZED, DOUBLE-BLIND, 
PLACEBO-CONTROLLED STUDY OF EN3835 IN THE 
TREATMENT OF EDEMATOUS FIBROSCLEROTIC 
PANNICULOPATHY 
IND 110077 
Amendment 2 
Date: 
Original Protocol: September 27, 2017 
Amendment 1: December 19, 2017 
Amendment 2: January 18, 2018 
Auxilium Pharmaceuticals, Inc. (Auxilium) was acquired by Endo International plc. in 
January 2015. The sponsor of the application remains as Auxilium Pharmaceuticals, LLC, 
1400 Atwater Drive, Malvern, PA; however, Endo Pharmaceuticals Inc. is authorized to act and 
to communicate on behalf of Auxilium. 
Confidentiality Statement 
 

EN3835-303 Protocol Amendment 2 
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Page 2 
 
 
 
2. 
SUMMARY OF CHANGES 
EN3835-303 protocol amendments and amended informed consent forms (as necessary) have 
been reviewed and approved by the governing Institutional Review Boards (IRBs) before 
implementation of the amendments at each study center. 
Amendment 2 was incorporated into the protocol on January 18, 2018. The major reasons for 
this amendment are revising the primary efficacy variable from at least one buttock to a 
randomly selected target buttock, revising key secondary endpoints, and adding an additional 
efficacy assessment. 
Section 
Original Text 
Revised Text 
4 Synopsis, 
Study Period 
Estimated date first subject enrolled: Feb-2018 
Estimated date last subject completed: 
Sep-2018 
Estimated date first subject enrolled: Feb-2018 
Estimated date last subject completed: 
Oct-2018 
4 Synopsis, 
Study Design 
Added text 
Of the two assigned eligible buttocks, one 
buttock will be randomly selected as the target 
buttock for the primary efficacy endpoint. The 
other (remaining) buttock will be considered 
the non-target buttock. Subjects, investigators, 
site personnel, and Endo personnel will be 
blinded to the identification of the target and 
the non-target buttocks. 
At Day 1, the subject will complete a Patient 
Reported Cellulite Impact Scale (PR-CIS) 
assessment. 
At Day 1, the subject will complete a Patient 
Reported Cellulite Impact Scale (PR-CIS) 
assessment and a Subject Self-Rating Scale 
(SSRS) assessment. 
4 Synopsis, 
Diagnosis and 
Inclusion/Ex-
clusion Criteria, 
Exclusion 
Criteria 
13. Was a subject in a previous cellulite 
clinical trial of collagenase clostridium 
histolyticum (CCH): AUX-CC-830, AUX-
CC-831, EN3835-102, EN3835-104, EN3835-
201, and/or EN3835-202 
13. Was a subject in a previous cellulite 
clinical trial of collagenase clostridium 
histolyticum (CCH): AUX-CC-830, AUX-
CC-831, EN3835-102, EN3835-104, EN3835-
201, EN3835-202, and/or EN3835-205 
4 Synopsis, 
Criteria for 
Evaluation, 
Efficacy 
• Subject using PR-PCSS while viewing 
digital image of the left buttock: 5-level 
scale ranging from 0 (no cellulite) to 4 
(severe cellulite) (Day 1 (Baseline) and 
Days 22, 43, and 71) for the left buttock 
• Subject using PR-PCSS while viewing 
digital image of the right buttock: 5-level 
scale ranging from 0 (no cellulite) to 4 
(severe cellulite) (Day 1 (Baseline) and 
Days 22, 43, and 71) for the right buttock 
• Investigator using the CR-PCSS by live 
assessment: 5-level scale ranging from 0 
(no cellulite) to 4 (severe cellulite) (Day 1 
(Baseline) and Days 22, 43, and 71) for the 
left buttock 
• Subject using PR-PCSS while viewing 
digital image of the target buttock: 5-level 
scale ranging from 0 (no cellulite) to 4 
(severe cellulite) (Day 1 (Baseline) and 
Days 22, 43, and 71) for the target buttock 
• Subject using PR-PCSS while viewing 
digital image of the non-target buttock: 5-
level scale ranging from 0 (no cellulite) to 
4 (severe cellulite) (Day 1 (Baseline) and 
Days 22, 43, and 71) for the non-target 
buttock 
• Investigator using the CR-PCSS by live 
assessment: 5-level scale ranging from 0 
(no cellulite) to 4 (severe cellulite) (Day 1 
(Baseline) and Days 22, 43, and 71) for the 
target buttock 

EN3835-303 Protocol Amendment 2 
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Page 3 
 
 
 
Section 
Original Text 
Revised Text 
• Investigator using the CR-PCSS by live 
assessment: 5-level scale ranging from 0 
(no cellulite) to 4 (severe cellulite) (Day 1 
(Baseline) and Days 22, 43, and 71) for the 
right buttock 
• Investigator Global Aesthetic Improvement 
Scale (I-GAIS): 7-level scale ranging from 
3 (very much improved) to −3 (very much 
worse) (Days 22, 43, and 71) for the left 
buttock 
• Investigator Global Aesthetic Improvement 
Scale (I-GAIS): 7-level scale ranging from 
3 (very much improved) to −3 (very much 
worse) (Days 22, 43, and 71) for the right 
buttock 
• Subject Global Aesthetic Improvement 
Scale (S-GAIS): 7-level scale ranging from 
3 (very much improved) to −3 (very much 
worse) (Days 22, 43, and 71) for the left 
buttock 
• Subject Global Aesthetic Improvement 
Scale (S-GAIS): 7-level scale ranging from 
3 (very much improved) to −3 (very much 
worse) (Days 22, 43, and 71) for the right 
buttock 
• Patient Reported Cellulite Impact Scale 
(PR-CIS): 6 questions with responses to 
each question consisting of a numerical 
rating scale (NRS) ranging from 0 (Not at 
all) to 10 (Extremely) 
• Subject satisfaction with cellulite treatment 
assessment: 5-level scale ranging from 2 
(very satisfied) to −2 (very dissatisfied) 
(Day 71) for both left and right buttocks 
• Investigator using the CR-PCSS by live 
assessment: 5-level scale ranging from 0 
(no cellulite) to 4 (severe cellulite) (Day 1 
(Baseline) and Days 22, 43, and 71) for the 
non-target buttock 
• Investigator Global Aesthetic Improvement 
Scale (I-GAIS): 7-level scale ranging from 
3 (very much improved) to −3 (very much 
worse) (Days 22, 43, and 71) for the target 
buttock 
• Investigator Global Aesthetic Improvement 
Scale (I-GAIS): 7-level scale ranging from 
3 (very much improved) to −3 (very much 
worse) (Days 22, 43, and 71) for the non-
target buttock 
• Subject Global Aesthetic Improvement 
Scale (S-GAIS): 7-level scale ranging from 
3 (very much improved) to −3 (very much 
worse) (Days 22, 43, and 71) for the target 
buttock 
• Subject Global Aesthetic Improvement 
Scale (S-GAIS): 7-level scale ranging from 
3 (very much improved) to −3 (very much 
worse) (Days 22, 43, and 71) for the non-
target buttock 
• Patient Reported Cellulite Impact Scale 
(PR-CIS): 6 questions with responses to 
each question consisting of a numerical 
rating scale (NRS) ranging from 0 (Not at 
all) to 10 (Extremely) 
• Subject Self-Rating Scale (SSRS): 7-level 
scale ranging from 0 (extremely 
dissatisfied) to 6 (extremely satisfied) (Day 
1 (Baseline) and Day 71) 
• Subject satisfaction with cellulite treatment 
assessment: 5-level scale ranging from 2 
(very satisfied) to −2 (very dissatisfied) 
(Day 71) for both left and right buttocks 
4 Synopsis, 
Criteria for 
Evaluation, 
Safety 
• Adverse events (AEs) (including those of 
special interest (AESI); which are adverse 
events such as bruising, ecchymosis, 
hematomas, and contusions that occur 
remote to the site of drug administration, or 
any hypersensitivity reactions, including 
anaphylaxis) 
• Adverse events (AEs) (including those of 
special interest (AESI); which are AEs 
such as bruising, ecchymosis, hematomas, 
and contusions that occur remote to the site 
of drug administration, or any 
hypersensitivity reactions, including 
anaphylaxis; and local AEs associated with 
the injection site, including bruising, pain, 
nodules/mass, ulceration, erythema, 
pruritus, swelling, and/or induration) 

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Section 
Original Text 
Revised Text 
4 Synopsis, 
Statistical 
Methods, 
Analyses, 
Analyses of 
Primary 
Endpoint 
The primary endpoint is the proportion of 2-
level composite responders at Day 71 defined 
as subjects with at least one of two treated 
buttocks with: 
• an improvement in severity from baseline 
(Day 1 visit) of at least 2 levels of severity 
in the CR-PCSS as assessed live by the 
Investigator, and 
• an improvement in severity from baseline 
of at least 2 levels of severity in the 
PR-PCSS as assessed by the subject while 
viewing the digital image of the same 
buttock. 
A subject will be considered a responder if 
these criteria are met in the left buttock or 
right buttock or both buttocks in that subject. 
The primary endpoint is the proportion of 2-
level composite responders at Day 71 defined 
as subjects with: 
• an improvement in severity from baseline 
(Day 1 visit) of at least 2 levels of severity 
in the CR-PCSS as assessed live by the 
Investigator of the target buttock, and 
• an improvement in severity from baseline 
of at least 2 levels of severity in the 
PR-PCSS as assessed by the subject while 
viewing the digital image of the target 
buttock. 
A subject will be considered a responder if 
these criteria are met in the randomized target 
buttock of that subject. 
4 Synopsis, 
Statistical 
Methods, 
Analyses, 
Analyses of Key 
Secondary 
Endpoints 
There will be 4 key secondary endpoints 
grouped as two families of 2 endpoints per 
family analyzed in a hierarchical order. 
• Family #1 – two endpoints: 
− Proportion of 1-level PR-PCSS responders 
defined as subjects with ≥1-level 
improvement in PR-PCSS severity rating 
of left buttock at Day 71 compared to 
Day 1 
− Proportion of 1-level PR-PCSS responders 
defined as subjects with ≥1-level 
improvement in PR-PCSS severity rating 
of right buttock at Day 71 compared to 
Day 1 
• Family #2 – two endpoints: 
− Proportion of 1-level S-GAIS responders 
defined as subjects with ≥1-level 
improvement (improved, much improved 
or very much improved) in the S-GAIS 
assessment of left buttock at Day 71 
− Proportion of 1-level S-GAIS responders 
defined as subjects with ≥1-level 
improvement (improved, much improved 
or very much improved) in the S-GAIS 
assessment of right buttock at Day 71 
There will be 8 key secondary endpoints 
grouped as three families of 2-4 endpoints per 
family analyzed in hierarchical order. 
• Family #1 – four endpoints: 
− Proportion of 1-level PR-PCSS responders 
defined as subjects with ≥1-level 
improvement in PR-PCSS severity rating 
of the target buttock at Day 71 compared to 
Day 1 
− Proportion of 2-level PR-PCSS responders 
defined as subjects with ≥2-level 
improvement in PR-PCSS severity rating 
of the target buttock at Day 71 compared to 
Day 1 
− Proportion of 1-level composite responders 
of the target buttock (defined as subjects 
with an improvement in severity from 
baseline of at least 1 level of severity in the 
CR-PCSS of the target buttock assessed 
live by the Investigator and an 
improvement of severity from baseline of 
at least 1 level of severity in the PR-PCSS 
of the target buttock) at Day 71 compared 
to Day 1 
− Proportion of 2-level composite responders 
of the non-target buttock at Day 71 
compared to Day 1 
• Family #2 – two endpoints: 
− Proportion of 1-level SSRS responders 
defined as subjects who were at least 
slightly satisfied at Day 71 (SSRS rating ≥ 
4)  
− Change from baseline (Day1) of the PR-
CIS at Day 71 

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Section 
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Revised Text 
 
• Family #3 – two endpoints: 
− Proportion of 1-level S-GAIS responders 
defined as subjects with ≥1-level 
improvement (improved, much improved 
or very much improved) in the S-GAIS 
assessment of the target buttock at Day 71 
− Proportion of 2-level S-GAIS responders 
defined as subjects with ≥2-level 
improvement (much improved or very 
much improved) in the S-GAIS assessment 
of the target buttock at Day 71 
The family #1 key secondary efficacy analyses 
will be performed only if the primary efficacy 
analysis is significant at a significance level of 
p ≤ 0.05 (gatekeeping strategy). Similarly, 
family #2 key secondary efficacy analyses will 
be performed only if at least one of the key 
secondary efficacy endpoints of family #1 is 
significant at a significance level of p ≤ 0.025 
(parallel gatekeeping strategy) 
The family #1 key secondary efficacy analyses 
will be performed only if the primary efficacy 
analysis is significant at a significance level of 
p ≤ 0.05 (gatekeeping strategy). Similarly, 
family #2 key secondary efficacy analyses will 
be performed only if at least one of the key 
secondary efficacy endpoints of family #1 is 
significant at a significance level of p ≤ 0.0125 
and family #3 key secondary efficacy analyses 
will be performed only if at least one of the 
key secondary efficacy endpoints of family #2 
is significant (parallel gatekeeping strategy). 
4 Synopsis, 
Statistical 
Methods, 
Analysis, 
Supportive 
Endpoints 
• Proportion of 2-level PR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 2 levels 
of severity in the PR-PCSS) of the left 
buttock (Days 22, 43, and 71) 
• Proportion of 2-level PR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 2 levels 
of severity in the PR-PCSS) of the right 
buttock (Days 22, 43, and 71) 
• Proportion of 1-level PR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the PR-PCSS) of the left 
buttock (Days 22, 43, and 71) 
• Proportion of 1-level PR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the PR-PCSS) of the right 
buttock (Days 22, 43, and 71)  
• Proportion of 2-level PR-PCSS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the left 
buttock or right buttock or both buttocks in 
that subject. 
• Proportion of 2-level PR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 2 levels 
of severity in the PR-PCSS) of the target 
buttock (Days 22, 43, and 71) 
• Proportion of 2-level PR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 2 levels 
of severity in the PR-PCSS) of the non-
target buttock (Days 22, 43, and 71) 
• Proportion of 1-level PR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the PR-PCSS) of the target 
buttock (Days 22, 43, and 71) 
• Proportion of 1-level PR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the PR-PCSS) of the non-
target buttock (Days 22, 43, and 71) 
• Proportion of 2-level PR-PCSS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the 
target buttock or non-target buttock or both 
buttocks in that subject. 

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Endo Pharmaceuticals Inc. 
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Section 
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Revised Text 
• Proportion of 1-level PR-PCSS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the left 
buttock or right buttock or both buttocks in 
that subject.  
• Proportion of 2-level PR-PCSS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both left and right buttocks. 
• Proportion of 1-level PR-PCSS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both left and right buttocks. 
• Proportion of 2-level CR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 2 levels 
of severity in the CR-PCSS) of the left 
buttock (Days 22, 43, and 71)  
• Proportion of 2-level CR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 2 levels 
of severity in the CR-PCSS) of the right 
buttock (Days 22, 43, and 71) 
• Proportion of 1-level CR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the CR-PCSS) of the left 
buttock (Days 22, 43, and 71) 
• Proportion of 1-level CR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the CR-PCSS) of the right 
buttock (Days 22, 43, and 71) 
• Proportion of 2-level CR-PCSS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the left 
buttock or right buttock or both buttocks in 
that subject 
• Proportion of 1-level CR-PCSS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the left 
buttock or right buttock or both buttocks in 
that subject 
• Proportion of 1-level PR-PCSS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the 
target buttock or non-target buttock or both 
buttocks in that subject.  
• Proportion of 2-level PR-PCSS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both the target and non-target 
buttocks. 
• Proportion of 1-level PR-PCSS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both the target and non-target 
buttocks. 
• Proportion of 2-level CR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 2 levels 
of severity in the CR-PCSS) of the target 
buttock (Days 22, 43, and 71)  
• Proportion of 2-level CR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 2 levels 
of severity in the CR-PCSS) of the non-
target buttock (Days 22, 43, and 71) 
• Proportion of 1-level CR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the CR-PCSS) of the target 
buttock (Days 22, 43, and 71) 
• Proportion of 1-level CR-PCSS responders 
(defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the CR-PCSS) of the non-
target buttock (Days 22, 43, and 71) 
• Proportion of 2-level CR-PCSS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the 
target buttock or non-target buttock or both 
buttocks in that subject 
• Proportion of 1-level CR-PCSS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the 
target buttock or non-target buttock or both 
buttocks in that subject 

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18-Jan-2018 
Endo Pharmaceuticals Inc. 
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Section 
Original Text 
Revised Text 
• Proportion of 2-level CR-PCSS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both left and right buttocks 
• Proportion of 1-level CR-PCSS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both left and right buttocks 
• Proportion of 1-level composite responders 
of the left buttock (defined as subjects with 
an improvement in severity from baseline 
of at least 1 level of severity in the CR-
PCSS of the left buttock assessed live by 
the Investigator and an improvement of 
severity from baseline of at least 1 level of 
severity in the PR-PCSS of that same left 
buttock) (Days 22, 43, and 71) 
• Proportion of 1-level composite responders 
of the right buttock (defined as subjects 
with an improvement in severity from 
baseline of at least 1 level of severity in the 
CR-PCSS of the right buttock assessed live 
by the Investigator and an improvement of 
severity from baseline of at least 1 level of 
severity in the PR-PCSS of that same right 
buttock) (Days 22, 43, and 71) 
• Proportion of 1-level composite responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the left 
buttock or right buttock or both buttocks in 
that subject. 
• Proportion of 1-level composite responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both left and right buttocks. 
• Proportion of 2-level composite responders 
of the left buttock (defined as subjects with 
an improvement in severity from baseline 
of at least 2 levels of severity in the CR-
PCSS of the left buttock assessed live by 
the Investigator and an improvement of 
severity from baseline of at least 2 levels of 
severity in the PR-PCSS of that same left 
buttock) (Days 22, 43, and 71) 
• Proportion of 2-level CR-PCSS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both the target and non-target 
buttocks 
• Proportion of 1-level CR-PCSS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both the target and non-target 
buttocks 
• Proportion of 1-level composite responders 
of the target buttock (defined as subjects 
with an improvement in severity from 
baseline of at least 1 level of severity in the 
CR-PCSS of the target buttock assessed 
live by the Investigator and an 
improvement of severity from baseline of 
at least 1 level of severity in the PR-PCSS 
of that same target buttock) (Days 22, 43, 
and 71) 
• Proportion of 1-level composite responders 
of the non-target buttock (defined as 
subjects with an improvement in severity 
from baseline of at least 1 level of severity 
in the CR-PCSS of the non-target buttock 
assessed live by the Investigator and an 
improvement of severity from baseline of 
at least 1 level of severity in the PR-PCSS 
of that same non-target buttock) (Days 22, 
43, and 71) 
• Proportion of 1-level composite responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the 
target buttock or non-target buttock or both 
buttocks in that subject. 
• Proportion of 1-level composite responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both the target and non-target 
buttocks.  
• Proportion of 2-level composite responders 
of the target buttock (defined as subjects 
with an improvement in severity from 
baseline of at least 2 levels of severity in 
the CR-PCSS of the target buttock assessed 
live by the Investigator and an 
improvement of severity from baseline of 
at least 2 levels of severity in the PR-PCSS 
of that same target buttock) (Days 22, 43, 
and 71) 

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18-Jan-2018 
Endo Pharmaceuticals Inc. 
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Section 
Original Text 
Revised Text 
• Proportion of 2-level composite responders 
of the right buttock (defined as subjects 
with an improvement in severity from 
baseline of at least 2 levels of severity in 
the CR-PCSS of the right buttock assessed 
live by the Investigator and an 
improvement of severity from baseline of 
at least 2 levels of severity in the PR-PCSS 
of that same right buttock) (Days 22, 43, 
and 71) 
• Proportion of 2-level composite responders 
of at least one of two buttocks (Days 22, 
43, and 71). A subject will be considered a 
responder if this criterion is met in the left 
buttock or right buttock or both buttocks in 
that subject.  
• Proportion of 2-level composite responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both left and right buttocks. 
• Proportion of subjects at each level of the 
S-GAIS of the left buttock (Days 22, 43, 
and 71) 
• Proportion of subjects at each level of the 
S-GAIS of the right buttock (Days 22, 43, 
and 71) 
• Proportion of 1-level S-GAIS responders 
defined as subjects with a response of at 
least 1 (improved) in the S- GAIS of the 
left buttock (Days 22, 43, and 71) 
• Proportion of 1-level S-GAIS responders 
defined as subjects with a response of at 
least 1 (improved) in the S- GAIS of the 
right buttock (Days 22, 43, and 71) 
• Proportion 1-level S-GAIS responders of at 
least one buttock (Days 22, 43, and 71). A 
subject will be considered a responder if 
this criterion is met in the left buttock or 
right buttock or both buttocks in that 
subject. 
• Proportion of 1-level S-GAIS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both left and right buttocks. 
• Proportion of subjects at each level of the 
I-GAIS of the left buttock (Days 22, 43, 
and 71) 
• Proportion of 2-level composite responders 
of the non-target buttock (defined as 
subjects with an improvement in severity 
from baseline of at least 2 levels of severity 
in the CR-PCSS of the non-target buttock 
assessed live by the Investigator and an 
improvement of severity from baseline of 
at least 2 levels of severity in the PR-PCSS 
of that same non-target buttock) (Days 22, 
43, and 71) 
• Proportion of 2-level composite responders 
of at least one of two buttocks (Days 22, 
43, and 71). A subject will be considered a 
responder if this criterion is met in the 
target buttock or non-target buttock or both 
buttocks in that subject.  
• Proportion of 2-level composite responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both the target and non-target 
buttocks. 
• Proportion of subjects at each level of the 
S-GAIS of the target buttock (Days 22, 43, 
and 71) 
• Proportion of subjects at each level of the 
S-GAIS of the non-target buttock (Days 
22, 43, and 71) 
• Proportion of 1-level S-GAIS responders 
defined as subjects with a response of at 
least 1 (improved) in the S-GAIS of the 
target buttock (Days 22, 43, and 71) 
• Proportion of 1-level S-GAIS responders 
defined as subjects with a response of at 
least 1 (improved) in the S-GAIS of the 
non-target buttock (Days 22, 43, and 71) 
• Proportion 1-level S-GAIS responders of at 
least one buttock (Days 22, 43, and 71). A 
subject will be considered a responder if 
this criterion is met in the target buttock or 
non-target buttock or both buttocks in that 
subject. 
• Proportion of 1-level S-GAIS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both the target and non-target 
buttocks. 
• Proportion of subjects at each level of the 
I-GAIS of the target buttock (Days 22, 43, 
and 71) 

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Endo Pharmaceuticals Inc. 
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Section 
Original Text 
Revised Text 
• Proportion of subjects at each level of the 
I-GAIS of the right buttock (Days 22, 43, 
and 71) 
• Proportion of 1-level I-GAIS responders 
(defined as subjects with a response of at 
least 1 (improved) in the Investigator GAIS 
assessment) of at least one buttock (Days 
22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in the left buttock or right buttock or 
both buttocks in that subject.  
• Proportion of 1-level I-GAIS responders of 
two buttocks in the same individual (Days 
22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both left and right buttocks. 
• Change from baseline (Day 1) of the PR-
CIS total score at Day 71 
• Change from baseline (Day 1) of the 
abbreviated PR-CIS score at Day 71 
• Proportion of subjects with a change from 
baseline (Day1) of the PR-CIS ≥12 at Day 
71 
• Proportion of subjects with a change from 
baseline (Day 1) of the abbreviated PR-CIS 
≥10 at Day 71 
• Proportion of subjects at each level of the 
subject satisfaction with cellulite treatment 
(Day 71) 
• Proportion of satisfied responders (defined 
as subjects with a response of at least 1 (ie, 
1 Satisfied or 2-Very Satisfied) in the 
subject satisfaction with cellulite treatment 
assessment (Day 71) 
• Proportion of subjects at each level of the 
I-GAIS of the non-target buttock (Days 22, 
43, and 71) 
• Proportion of 1-level I-GAIS responders 
defined as subjects with a response of at 
least 1 (improved) in the I-GAIS of the 
target buttock (Days 22, 43, and 71) 
• Proportion of 1-level I-GAIS responders 
defined as subjects with a response of at 
least 1 (improved) in the I-GAIS of the 
non-target buttock (Days 22, 43, and 71) 
• Proportion of 1-level I-GAIS responders of 
at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if 
this criterion is met in the target buttock or 
non-target buttock or both buttocks in that 
subject.  
• Proportion of 1-level I-GAIS responders of 
two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both the target and non-target 
buttocks. 
• Change from baseline (Day 1) of the 
PR-CIS score at Day 71 
• Change from baseline (Day 1) of the 
abbreviated PR-CIS score at Day 71 
• Proportion of subjects with a change from 
baseline (Day1) of the PR-CIS ≥12 at 
Day 71 
• Proportion of subjects with a change from 
baseline (Day 1) of the abbreviated PR-CIS 
≥10 at Day 71 
• Proportion of subjects at each level of the 
subject self-rating scale (SSRS) (Day 1 
(Baseline) and Day 71 
• Proportion of 1-level SSRS responders 
defined as subjects who were at least 
slightly satisfied at Day 71 (SSRS rating 
≥ 4) 
• Proportion of subjects at each level of the 
subject satisfaction with cellulite treatment 
assessment (Day 71) 
• Proportion of satisfied responders (defined 
as subjects with a response of at least 1 (ie, 
1 Satisfied or 2-Very Satisfied) in the 
subject satisfaction with cellulite treatment 
assessment (Day 71) 

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Section 
Original Text 
Revised Text 
5 Schedule of 
Events 
Added table row 
• Subject Self-Rating Scale (SSRS) 
Day 1 Treatment Visit 1: Xc 
Day 71 (+ 5d)/End of Study/Early 
Termination: X 
7 List of 
Abbreviations, 
Table 2: 
Abbreviations 
and Special 
Terms 
Added table rows 
SSRS: Subject Self-Rating Scale 
MI: Multiple imputation 
11.2 Subject 
Exclusion 
Criteria 
13. Was a subject in a previous cellulite 
clinical trial of CCH: AUX-CC-830, 
AUX-CC-831, EN3835-102, EN3835-
104, EN3835-201, and/or EN3835-202 
13. Was a subject in a previous cellulite 
clinical trial of CCH: AUX-CC-830, 
AUX-CC-831, EN3835-102, EN3835-
104, EN3835-201, EN3835-202, and/or 
EN3835-205 
12.4.1 Treatment 
Visit 1: 
Pre-Injection 
Added text 
6. Subjects will complete the SSRS 
assessment (section 13.1.2.5); the 
Investigator is blinded to these ratings 
Added text 
9. Upon confirmation of two buttocks 
eligible for treatment (eligible criteria 
being each buttock have PR-PCSS and 
CR-PCSS scores of 3 or 4), the IWRS 
system will randomly assign one buttock 
as the target buttock in the background. 
Subjects, investigators, site personnel and 
Endo personnel will be blinded to target 
buttock assignment. 
8. Randomization of subjects with two 
buttocks eligible for treatment (eligible 
criteria being each buttock have PR-PCSS 
and CR-PCSS scores of 3 or 4) to 
treatment (section 12.10); obtain kit 
numbers of study treatment 
10. Randomization of subjects with two 
buttocks eligible for treatment (eligible 
criteria being each buttock have PR-PCSS 
and CR-PCSS scores of 3 or 4) to 
treatment (section 12.10); obtain kit 
numbers of study treatment. Subjects, 
investigators, site personnel, and Endo 
personnel will be blinded to treatment 
assignment. 

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12.6 Day 71 
(+5 days) / End 
of Study / Early 
Termination 
6. Subject Cellulite Assessment of each of the 
two buttocks using the photographic image 
before marking dimples and injection sites 
(NOTE: complete subject cellulite 
assessments before Investigator cellulite 
assessments) using: 
a. Patient Reported Photonumeric Cellulite 
Severity Scale (PR-PCSS) assessment 
(section 13.1.2.1) 
b. Subject Global Aesthetic Improvement 
Scale (S-GAIS) (section 13.1.2.2) 
c. Patient Reported Cellulite Impact Scale 
(PR-CIS) assessment (section 13.1.2.3); 
note this assessment is of both left and 
right buttocks rather than each individual 
buttock 
d. Subject Satisfaction with Cellulite 
Treatment Assessment (section 13.1.2.4); 
note this assessment is of both left and 
right buttocks rather than each individual 
buttock 
6. Subject Cellulite Assessment of each of the 
two buttocks using the photographic image 
before marking dimples and injection sites 
(NOTE: complete subject cellulite 
assessments before Investigator cellulite 
assessments) using: 
a. Patient Reported Photonumeric Cellulite 
Severity Scale (PR-PCSS) assessment 
(section 13.1.2.1) 
b. Subject Global Aesthetic Improvement 
Scale (S-GAIS) (section 13.1.2.2) 
c. Patient Reported Cellulite Impact Scale 
(PR-CIS assessment (section 13.1.2.3); 
note this assessment is of both left and 
right buttocks rather than each individual 
buttock 
d. Subject Satisfaction with Cellulite 
Treatment Assessment (section 13.1.2.4); 
note this assessment is of both left and 
right buttocks rather than each individual 
buttock 
e. Subject Self-Rating Scale assessment 
(section 13.1.2.5); note this assessment is 
of both left and right buttocks rather than 
each individual buttock 
12.10 Blinding 
and 
Randomization 
On Day 1, if each of the buttocks again meet 
the criteria (3 or 4 on the PR-PCSS and CR-
PCSS), the subject will be randomized to a 
treatment group. 
On Day 1, if each of the buttocks (ie, both 
buttocks) again meet the criteria (3 or 4 on 
the PR-PCSS and CR-PCSS), one buttock 
will be randomly assigned by the IWRS as 
the target buttock for the primary efficacy 
endpoint. Subjects, investigators, site 
personnel and Endo personnel will be blinded 
to the identification of the target buttock.  
On Day 1, if each of the buttocks (ie, both 
buttocks) again meet the criteria (3 or 4 on 
the PR-PCSS and CR-PCSS), the subject will 
be randomized to a treatment group.  

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13.1.2.5 Subject 
Self-Rating Scale 
(SSRS) 
Added section 
13.1.2.5. Subject Self-Rating Scale (SSRS) 
The SSRS is a measure that assesses subject 
satisfaction with appearance in association 
with cellulite on the buttocks using whole 
numbers on a 7-level scale that ranges from 0 
(extremely dissatisfied) to 6 (extremely 
satisfied). The patient will be asked to respond 
to the question related to the satisfaction with 
appearance of the cellulite on their buttocks on 
the appropriate visit day (note Day 71 question 
is different than Day 1 question). No 
photographs or reference to previous ratings or 
evaluations will be used. Subjects will be 
given a list of responses and they will provide 
a rating from those below that best represents 
their answer (Table 7); the list of responses is 
the same for Day 1 and for Day 71. 
On Day 1 (Baseline), subjects will be 
instructed to answer: Considering your 
appearance in association with your cellulite 
on your buttocks, how satisfied do you feel 
with your appearance at the present time? 
On Day 71, subjects will be instructed to 
answer: Considering your appearance in 
association with your cellulite on your 
buttocks, how satisfied do you feel with your 
appearance at the present time whether or not 
in your judgment it is due entirely to treatment 
with EN3835? 
This variable will be entered directly into the 
EDC system, thus the electronic database will 
serve as the direct point of data capture and 
will serve as source for this variable. 
Table 7: Subject Self-Rating Scale (SSRS) 
Rating 
Response Option 
6 
Extremely satisfied 
5 
Satisfied 
4 
Slightly satisfied 
3 
Neither satisfied nor dissatisfied 
2 
Slightly dissatisfied 
1 
Dissatisfied 
0 
Extremely dissatisfied 

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14.6.1 Adverse 
Events of Special 
Interest 
Adverse events such as bruising, ecchymosis, 
hematomas, and contusions that occur remote 
to the site of drug administration, or any 
hypersensitivity reactions, including 
anaphylaxis, will be recorded as an AE or 
SAE as appropriate (see section 14.1.1, 
Adverse Events or section 14.1.2, Serious 
Adverse Events). 
Adverse events such as bruising, ecchymosis, 
hematomas, and contusions that occur remote 
to the site of drug administration, or any 
hypersensitivity reactions, including 
anaphylaxis, will be recorded and evaluated 
for seriousness and severity (see section 
14.1.1, Adverse Events or section 14.1.2, 
Serious Adverse Events). 
In addition, local AEs associated with the 
injection site, including bruising, pain, 
nodules/mass, ulceration, erythema, pruritus, 
swelling, and/or induration, will be recorded 
and evaluated for seriousness and severity (see 
as appropriate, section 14.1.1, Adverse Events 
or section 14.1.2, Serious Adverse Events) 
17.1 
Determination of 
Sample Size 
The primary variable is the proportion of 2-
level composite responders at Day 71 defined 
as subjects with at least one of two treated 
buttocks with: 
• an improvement in severity from baseline 
(Day 1 visit) of at least 2 levels of severity 
in the CR-PCSS as assessed live by the 
Investigator, and  
• an improvement in severity from baseline 
of at least 2 levels of severity in the 
PR-PCSS as assessed by the subject while 
viewing the digital image of the same 
buttock.  
A subject will be considered a responder if 
these criteria are met in either the left buttock 
or right buttock or both buttocks in that 
subject. In other words, a subject will be 
considered a responder if she has an 
improvement of at least 2 levels on the PR-
PCSS and an improvement of at least 2 levels 
on the CR-PCSS on that same buttock; that 
buttock could be the left buttock or right 
buttock or both buttocks. 
The primary variable is the proportion of 2-
level composite responders at Day 71 defined 
as subjects with: 
• an improvement in severity from baseline 
(Day 1 visit) of at least 2 levels of severity 
in the CR-PCSS as assessed live by the 
Investigator of the target buttock, and  
• an improvement in severity from baseline 
of at least 2 levels of severity in the 
PR-PCSS as assessed by the subject while 
viewing the digital image of the target 
buttock.  
A subject will be considered a responder if 
these criteria are met in the randomized target 
buttock of that subject 

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17.2.3 Modified 
Intent-to-Treat 
(mITT) 
Population 
The mITT population is defined as all intent-
to-treat subjects with a baseline and at least 1 
post-injection evaluation of both the 
Investigator CR-PCSS and subject PR-PCSS 
for both left and right buttocks.. 
The mITT population is defined as all intent-
to-treat subjects with a baseline and at least 1 
post-injection evaluation of both the 
Investigator CR-PCSS and subject PR-PCSS 
for both the target and non-target buttocks.  
17.2.4 Per-
Protocol (PP) 
Population 
The per-protocol population is defined as the 
mITT subjects without any major protocol 
deviation that will impact the subject’s 
efficacy and safety.  
The per-protocol population is defined as the 
mITT subjects without any of the following:  
• Placebo-assigned subject receives EN3835 
treatment 
• EN3835-assigned subject receives placebo 
treatment only throughout the study 
• Any subject receives protocol-prohibited 
medications 
• Subject lacking PR-PCSS and/or CR-PCSS 
assessment at Day 71 
• Any major protocol deviation that is 
deemed as impacting subject efficacy 
17.5 Efficacy 
Analysis 
Changes in the PR-PCSS ratings and CR-
PCSS ratings from baselines, S-GAIS scores, 
and I-GAIS scores will be analyzed using the 
Wilcoxon rank sum test. 
Changes in the PR-PCSS ratings and CR-
PCSS ratings from baselines, S-GAIS scores, 
I-GAIS scores, and SSRS scores will be 
analyzed using the Wilcoxon rank sum test. 
Changes in PR-CIS from baselines will be 
analyzed using an analysis of covariance 
(ANCOVA) adjusted for baseline values. 
Similarly family #2 key secondary efficacy 
analyses will be performed only if at least one 
of the key secondary efficacy endpoints of 
family #1 is significant (p ≤ 0.025; parallel 
gatekeeping strategy 
Similarly family #2 key secondary efficacy 
analyses will be performed only if at least one 
of the key secondary efficacy endpoints of 
family #1 is significant (p ≤ 0.0125; parallel 
gatekeeping strategy) and family #3 key 
secondary efficacy analyses will be performed 
only if at least one of the key secondary 
efficacy endpoints of family #2 is significant 
(parallel gatekeeping strategy). 
Changes in the PR-PCSS ratings and CR-
PCSS ratings from baselines, S-GAIS scores, 
and I-GAIS scores will be analyzed using the 
Wilcoxon rank sum test. 
Changes in the PR-PCSS ratings and CR-
PCSS ratings from baselines, S-GAIS scores, 
I-GAIS scores, and SSRS scores will be 
analyzed using the Wilcoxon rank sum test. 

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17.5.1 Primary 
Efficacy 
Variable 
The primary efficacy variable is the proportion 
of 2-level composite responders at Day 71 
defined as subjects with at least one of two 
treated buttocks with: 
• an improvement in severity from baseline 
(Day 1 visit) of at least 2 levels of severity 
in the CR-PCSS as assessed live by the 
Investigator, and  
• an improvement in severity from baseline 
of at least 2 levels of severity in the 
PR-PCSS by the subject while viewing the 
digital image of the same buttock. 
A subject will be considered a responder if 
these criteria are met in either the left buttock 
or right buttock or both buttocks in that 
subject. In other words, a subject will be 
considered a responder if she has an 
improvement of at least 2 levels on the PR-
PCSS and an improvement of at least 2 levels 
on the CR-PCSS on that same buttock; that 
buttock could be the left buttock or right 
buttock or both buttocks. 
The primary efficacy variable is the proportion 
of 2-level composite responders at Day 71 
defined as subjects with: 
• an improvement in severity from baseline 
(Day 1 visit) of at least 2 levels of severity 
in the CR-PCSS as assessed live by the 
Investigator of the target buttock, and  
• an improvement in severity from baseline 
of at least 2 levels of severity in the 
PR-PCSS by the subject while viewing the 
digital image of the target buttock. 
A subject will be considered a responder if 
these criteria are met in the randomized target 
buttock of that subject. 
17.5.2.1 Key 
Secondary 
Variables 
There will be 4 key secondary endpoints 
grouped in two families of 2 endpoints per 
family analyzed in a hierarchical order. 
• Family #1 – two endpoints: 
− Proportion of 1-level PR-PCSS responders 
defined as subjects with ≥1-level 
improvement in PR-PCSS severity rating 
of left buttock at Day 71 compared to 
Day 1 
− Proportion of 1-level PR-PCSS responders 
defined as subjects with ≥1-level 
improvement in PR-PCSS severity rating 
of right buttock at Day 71 compared to 
Day 1 
There will be 8 key secondary endpoints 
grouped in three families of 2-4 endpoints per 
family analyzed in hierarchical order. 
• Family #1 – four endpoints: 
− Proportion of 1-level PR-PCSS responders 
defined as subjects with ≥1-level 
improvement in PR-PCSS severity rating 
of target buttock at Day 71 compared to 
Day 1 
− Proportion of 2-level PR-PCSS responders 
defined as subjects with ≥2-level 
improvement in PR-PCSS severity rating 
of target buttock at Day 71 compared to 
Day 1 
− Proportion of 1-level composite responders 
of target buttock (defined as subjects with 
an improvement in severity from baseline 
of at least 1 level of severity in the CR-
PCSS of the target buttock assessed live by 
the Investigator and an improvement of 
severity from baseline of at least 1 level of 
severity in the PR-PCSS of the target 
buttock) at Day 71 compared to Day 1 
− Proportion of 2-level composite responders 
of non-target buttock at Day 71 compared 
to Day 1 

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• Family #2 – two endpoints: 
− Proportion of 1-level S-GAIS responders 
defined as subjects with ≥1-level 
improvement (improved, much improved 
or very much improved) in the S- GAIS 
assessment of left buttock at Day 71 
− Proportion of 1-level S-GAIS responders 
defined as subjects with ≥1-level 
improvement (improved, much improved 
or very much improved) in the S-GAIS 
assessment of right buttock at Day 71 
• Family #2 – two endpoints: 
− Proportion of 1-level SSRS responders 
defined as subjects who were at least 
slightly satisfied at Day 71 (SSRS rating ≥ 
4)  
− Proportion of subjects with a change from 
baseline (Day1) of the PR-CIS ≥12 at Day 
71 
• Family #3 – two endpoints: 
− Proportion of 1-level S-GAIS responders 
defined as subjects with ≥1-level 
improvement (improved, much improved 
or very much improved) in the S-GAIS 
assessment of the target buttock at Day 71 
− Proportion of 2-level S-GAIS responders 
defined as subjects with ≥2-level 
improvement (much improved or very 
much improved) in the S-GAIS assessment 
of the target buttock at Day 71 
Added text 
Sensitivity analyses for the key secondary 
endpoints will include: 
• ITT subjects with missing data handled by 
multiple imputation (MI) approach 
• ITT subjects with missing data handled by 
an LOCF approach 
• mITT subjects with missing data handled 
by an LOCF approach 
• Observed data only (no missing data 
handling) 
• Per-protocol (PP) subjects with missing 
data handled by an LOCF approach if 10% 
or more subjects are excluded in the PP 
population from mITT population 

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17.5.3.1 
Supportive 
Variables 
• 
Proportion of 2-level PR-PCSS responders 
defined as subjects with an improvement 
in severity from baseline of at least 2 
levels of severity in the PR-PCSS of the 
left buttock (Days 22, 43, and 71) 
• 
Proportion of 2-level PR-PCSS responders 
defined as subjects with an improvement 
in severity from baseline of at least 2 
levels of severity in the PR-PCSS of the 
right buttock (Days 22, 43, and 71) 
• 
Proportion of 1-level PR-PCSS responders 
defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the PR-PCSS of left buttock 
(Days 22, 43, and 71) 
• 
Proportion of 1-level PR-PCSS responders 
defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the PR-PCSS of right 
buttock (Days 22, 43, and 71) 
• 
Proportion of 2-level PR-PCSS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the left 
buttock or right buttock or both buttocks 
in that subject. 
• 
Proportion of 1-level PR-PCSS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the left 
buttock or right buttock or both buttocks 
in that subject.  
• 
Proportion of 2-level PR-PCSS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both left and right buttocks. 
• 
Proportion of 1-level PR-PCSS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both left and right buttocks. 
• 
Proportion of 2-level PR-PCSS responders 
defined as subjects with an improvement 
in severity from baseline of at least 2 
levels of severity in the PR-PCSS of the 
target buttock (Days 22, 43, and 71) 
• 
Proportion of 2-level PR-PCSS responders 
defined as subjects with an improvement 
in severity from baseline of at least 2 
levels of severity in the PR-PCSS of the 
non-target buttock (Days 22, 43, and 71) 
• 
Proportion of 1-level PR-PCSS responders 
defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the PR-PCSS of the target 
buttock (Days 22, 43, and 71) 
• 
Proportion of 1-level PR-PCSS responders 
defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the PR-PCSS of the non-
target buttock (Days 22, 43, and 71) 
• 
Proportion of 2-level PR-PCSS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the 
target buttock or non-target buttock or 
both buttocks in that subject. 
• 
Proportion of 1-level PR-PCSS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the 
target buttock or non-target buttock or 
both buttocks in that subject.  
• 
Proportion of 2-level PR-PCSS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both the target and non-target 
buttocks. 
• 
Proportion of 1-level PR-PCSS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both the target and non-target 
buttocks. 

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• 
Proportion of 1-level composite 
responders of the left buttock (defined as 
subjects with an improvement in severity 
from baseline of at least 1 level of severity 
in the CR-PCSS of the left buttock 
assessed live by the Investigator and an 
improvement of severity from baseline of 
at least 1 level of severity in the PR-PCSS 
of that same left buttock) (Days 22, 43, 
and 71) 
• 
Proportion of 1-level composite 
responders of the right buttock (defined as 
subjects with an improvement in severity 
from baseline of at least 1 level of severity 
in the CR-PCSS of the right buttock 
assessed live by the Investigator and an 
improvement of severity from baseline of 
at least 1 level of severity in the PR-PCSS 
of that same right buttock) (Days 22, 43, 
and 71) 
• 
Proportion of 1-level composite 
responders of at least one buttock (Days 
22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in the left buttock or right buttock or 
both buttocks in that subject. 
• 
Proportion of 1-level composite 
responders of two buttocks in the same 
individual (Days 22, 43, and 71). A 
subject will be considered a responder if 
this criterion is met in both left and right 
buttocks. 
• 
Proportion of 2-level composite 
responders of the left buttock (defined as 
subjects with an improvement in severity 
from baseline of at least 2 levels of 
severity in the CR-PCSS of the left 
buttock assessed live by the Investigator 
and an improvement of severity from 
baseline of at least 2 levels of severity in 
the PR-PCSS of that same left buttock) 
(Days 22, 43, and 71) 
• 
Proportion of 2-level composite 
responders of the right buttock (defined as 
subjects with an improvement in severity 
from baseline of at least 2 levels of 
severity in the CR-PCSS of the right 
buttock assessed live by the Investigator 
and an improvement of severity from 
baseline of at least 2 levels of severity in 
the PR-PCSS of that same right buttock) 
(Days 22, 43, and 71) 
• 
Proportion of 1-level composite 
responders of the target buttock (defined 
as subjects with an improvement in 
severity from baseline of at least 1 level of 
severity in the CR-PCSS of the target 
buttock assessed live by the Investigator 
and an improvement of severity from 
baseline of at least 1 level of severity in 
the PR-PCSS of that same target buttock) 
(Days 22, 43, and 71) 
• 
Proportion of 1-level composite 
responders of the non-target buttock 
(defined as subjects with an improvement 
in severity from baseline of at least 1 level 
of severity in the CR-PCSS of the non-
target buttock assessed live by the 
Investigator and an improvement of 
severity from baseline of at least 1 level of 
severity in the PR-PCSS of that same 
non-target buttock) (Days 22, 43, and 71) 
• 
Proportion of 1-level composite 
responders of at least one buttock (Days 
22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in the target buttock or non-target 
buttock or both buttocks in that subject. 
• 
Proportion of 1-level composite 
responders of two buttocks in the same 
individual (Days 22, 43, and 71). A 
subject will be considered a responder if 
this criterion is met in both the target and 
non-target buttocks. 
• 
Proportion of 2-level composite 
responders of the target buttock (defined 
as subjects with an improvement in 
severity from baseline of at least 2 levels 
of severity in the CR-PCSS of the target 
buttock assessed live by the Investigator 
and an improvement of severity from 
baseline of at least 2 levels of severity in 
the PR-PCSS of that same target buttock) 
(Days 22, 43, and 71) 
• 
Proportion of 2-level composite 
responders of the non-target buttock 
(defined as subjects with an improvement 
in severity from baseline of at least 2 
levels of severity in the CR-PCSS of the 
non-target buttock assessed live by the 
Investigator and an improvement of 
severity from baseline of at least 2 levels 
of severity in the PR-PCSS of that same 
non-target buttock) (Days 22, 43, and 71) 

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• 
Proportion of 2-level composite 
responders of at least one of two buttocks 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in the left buttock or right buttock or 
both buttocks in that subject.  
• 
Proportion of 2-level composite 
responders of two buttocks in the same 
individual (Days 22, 43, and 71). A 
subject will be considered a responder if 
this criterion is met in both left and right 
buttocks. 
• 
Proportion of subjects at each level of the 
S-GAIS of the left buttock (Days 22, 43, 
and 71) 
• 
Proportion of subjects at each level of the 
S-GAIS of the right buttock (Days 22, 43, 
and 71) 
• 
Proportion of 1-level S-GAIS responders 
defined as subjects with a response of at 
least 1 (improved) in the S- GAIS of the 
left buttock (Days 22, 43, and 71) 
• 
Proportion of 1-level S-GAIS responders 
defined as subjects with a response of at 
least 1 (improved) in the S- GAIS of the 
right buttock (Days 22, 43, and 71) 
• 
Proportion 1-level S-GAIS responders of 
at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if 
this criterion is met in the left buttock or 
right buttock or both buttocks in that 
subject. 
• 
Proportion of 1-level S-GAIS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both left and right buttocks. 
• 
Proportion of subjects at each level of the 
I-GAIS of the left buttock (Days 22, 43, 
and 71) 
• 
Proportion of subjects at each level of the 
I-GAIS of the right buttock (Days 22, 43, 
and 71) 
• 
Proportion of 2-level composite 
responders of at least one of two buttocks 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in the target buttock or non-target 
buttock or both buttocks in that subject.  
• 
Proportion of 2-level composite 
responders of two buttocks in the same 
individual (Days 22, 43, and 71). A 
subject will be considered a responder if 
this criterion is met in both the target and 
non-target buttocks. 
• 
Proportion of subjects at each level of the 
S-GAIS of the target buttock (Days 22, 
43, and 71) 
• 
Proportion of subjects at each level of the 
S-GAIS of the non-target buttock 
(Days 22, 43, and 71) 
• 
Proportion of 1-level S-GAIS responders 
defined as subjects with a response of at 
least 1 (improved) in the S-GAIS of the 
target buttock (Days 22, 43, and 71) 
• 
Proportion of 1-level S-GAIS responders 
defined as subjects with a response of at 
least 1 (improved) in the S-GAIS of the 
non-target buttock (Days 22, 43, and 71) 
• 
Proportion 1-level S-GAIS responders of 
at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if 
this criterion is met in the target buttock or 
non-target buttock or both buttocks in that 
subject. 
• 
Proportion of 1-level S-GAIS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both the target and non-target right 
buttocks. 
• 
Proportion of subjects at each level of the 
I-GAIS of the target buttock (Days 22, 43, 
and 71) 
• 
Proportion of subjects at each level of the 
I-GAIS of the non-target buttock 
(Days 22, 43, and 71) 

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• 
Proportion of 1-level I-GAIS responders 
(defined as subjects with a response of at 
least 1 (improved) in the Investigator 
GAIS assessment) of at least one buttock 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in the left buttock or right buttock or 
both buttocks in that subject.  
• 
Proportion of 1-level I-GAIS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both left and right buttocks. 
• 
Change from baseline (Day 1) of the 
PR-CIS total score at Day 71 
• 
Change from baseline (Day 1) of the 
abbreviated PR-CIS score at Day 71 
• 
Proportion of subjects with a change from 
baseline (Day 1) of the PR-CIS ≥ 12 at 
Day 71 
• 
Proportion of subjects with a change from 
baseline (Day 1) of the abbreviated 
PR-CIS ≥ 10 at Day 71 
• 
Proportion of subjects at each level of the 
subject satisfaction with cellulite 
treatment (Day 71) 
• 
Proportion of satisfied responders (defined 
as subjects with a response of at least 1 
(ie, 1 Satisfied or 2 Very Satisfied) in the 
subject satisfaction with cellulite 
treatment assessment (Day 71) 
• 
Proportion of 1-level I-GAIS responders 
defined as subjects with a response of at 
least 1 (improved) in the I-GAIS of the 
target buttock (Days 22, 43, and 71) 
• 
Proportion of 1-level I-GAIS responders 
defined as subjects with a response of at 
least 1 (improved) in the I-GAIS of the 
non-target buttock (Days 22, 43, and 71) 
• 
Proportion of 1-level I-GAIS responders 
of at least one buttock (Days 22, 43, and 
71). A subject will be considered a 
responder if this criterion is met in the 
target buttock or non-target buttock or 
both buttocks in that subject.  
• 
Proportion of 1-level I-GAIS responders 
of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be 
considered a responder if this criterion is 
met in both the target and non-target 
buttocks. 
• 
Change from baseline (Day 1) of the 
PR-CIS total score at Day 71 
• 
Change from baseline (Day 1) of the 
abbreviated PR-CIS score at Day 71 
• 
Proportion of subjects with a change from 
baseline (Day 1) of the PR-CIS ≥ 12 at 
Day 71 
• 
Proportion of subjects with a change from 
baseline (Day 1) of the abbreviated 
PR-CIS ≥ 10 at Day 71 
• 
Proportion of subjects at each level of the 
SSRS (Day 1 (Baseline) and Day 71) 
• 
Proportion of 1-level SSRS responders 
defined as subjects who were at least 
slightly satisfied at Day 71 (SSRS rating 
≥ 4) 
• 
Proportion of subjects at each level of the 
subject satisfaction with cellulite treatment 
assessment (Day 71) 
• 
Proportion of satisfied responders (defined 
as subjects with a response of at least 1 
(ie, 1 Satisfied or 2 Very Satisfied) in the 
subject satisfaction with cellulite treatment 
assessment (Day 71) 

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4 Synopsis, 
Diagnosis and 
Inclusion/ 
Exclusion 
Criteria, 
Exclusion 
Criteria  
2. Has any of the following local conditions 
in the areas to be treated: 
a. History of lower extremity thrombosis or 
post-thrombosis syndrome 
b. Vascular disorder (eg, varicose veins, 
telangiectasia) in area to be treated 
c. Inflammation or active infection 
d. Active cutaneous alteration including rash, 
eczema, psoriasis, or skin cancer 
e. Has a tattoo and/or a mole located within 
2 cm of the site of injection  
2. Has any of the following local conditions 
in the areas to be treated: 
a. History of lower extremity thrombosis or 
post-thrombosis syndrome 
b. Vascular disorder (eg, varicose veins, 
telangiectasia) in area to be treated 
c. Inflammation or active infection 
d. Severe skin laxity, flaccidity, and/or 
sagging  
e. Active cutaneous alteration including rash, 
eczema, psoriasis, or skin cancer 
f. Has a tattoo and/or a mole located within 
2 cm of the site of injection 
4 Synopsis, 
Criteria for 
Evaluation, 
Efficacy 
Added text 
• Patient Reported Cellulite Impact Scale: 6 
questions with responses to each question 
consisting of a numerical rating scale 
(NRS) ranging from 0 (Not at all) to 10 
(Extremely) 
4 Synopsis, 
Statistical 
Methods, 
Analysis, 
Supportive 
Endpoints 
Added text 
• Change from baseline (Day 1) of the 
PR-CIS total score at Day 71 
• Change from baseline (Day 1) of the 
abbreviated PR-CIS score at Day 71 
• Proportion of subjects with a change from 
baseline (Day1) of the PR-CIS ≥12 at 
Day 71 
• Proportion of subjects with a change from 
baseline (Day 1) of the abbreviated PR-CIS 
≥10 at Day 71 
5 Schedule of 
Events, Physical 
examination 
Day -14 to -1 Screening: X 
Day 71 (+ 5d)/End of Study/Early 
Termination: X 
Day -14 to -1 Screening: X 
5 Schedule of 
Events, Subject 
cellulite 
assessments, 
Patient Reported 
Cellulite Impact 
Scale (PR-CIS) 
Added table row 
• Patient Reported Cellulite Impact Scale 
(PR-CIS) 
Day 1 Treatment Visit 1: Xc,g 
Day 71 (+ 5d)/End of Study/Early 
Termination: Xg 
5 Schedule of 
Events, 
Investigator 
cellulite 
assessments, 
Hexsel Cellulite 
Severity Scale 
(CSS) 
• Hexsel Cellulite Severity Scale (CSS) 
Day -14 to -1 Screening: Xb,i 
Day 1 Treatment Visit 1: Xc,b,i 
Deleted table row 

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5 Schedule of 
Events, Table 
footnotes 
i Initial Hexsel CSS at Screening must be ≤13 
on each of 2 bilateral buttocks and the 
buttocks must again be ≤13 at Day 1 visit  
Deleted text 
j Before randomization, each of the subject’s 
buttocks must have ratings of 3 or 4 (moderate 
or severe) in both the CR-PCSS and 
PR-PCSS, and Hexsel CSS score ≤13. 
i Before randomization, each of the subject’s 
buttocks must have ratings of 3 or 4 (moderate 
or severe) in both the CR-PCSS and 
PR-PCSS. 
7. List of 
Abbreviations, 
Table 2: 
Abbreviations 
and Special 
Terms 
CSS: Cellulite severity scale 
Deleted table row 
Added table row 
PR-CIS: Patient Reported Cellulite Impact 
Scale 
11.1 Subject 
Inclusion Criteria 
3. At Screening visit, have 2 bilateral 
buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as 
reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as 
reported by the Investigator (CR-PCSS), 
and 
c. a Hexsel CSS score no greater than 13 
3. At Screening visit, have 2 bilateral 
buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as 
reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as 
reported by the Investigator (CR-PCSS) 
4. At Day 1 visit, have 2 bilateral buttocks 
with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as 
reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as 
reported by the Investigator (CR-PCSS), 
and 
c. a Hexsel CSS score no greater than 13 
4. At Day 1 visit, have 2 bilateral buttocks 
with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as 
reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as 
reported by the Investigator (CR-PCSS)  
11.2 Subject 
Exclusion 
Criteria 
2. Has any of the following local conditions 
in the areas to be treated: 
a. History of lower extremity thrombosis or 
post-thrombosis syndrome 
b. Vascular disorder (eg, varicose veins, 
telangiectasia) in area to be treated 
c. Inflammation or active infection 
d. Active cutaneous alteration including rash, 
eczema, psoriasis, or skin cancer 
e. Has a tattoo and/or a mole located within 2 
cm of the site of injection 
2. Has any of the following local conditions 
in the areas to be treated: 
a. History of lower extremity thrombosis or 
post-thrombosis syndrome 
b. Vascular disorder (eg, varicose veins, 
telangiectasia) in area to be treated 
c. Inflammation or active infection 
d. Severe skin laxity, flaccidity, and/or 
sagging 
e. Active cutaneous alteration including rash, 
eczema, psoriasis, or skin cancer 
f. Has a tattoo and/or a mole located within 
2 cm of the site of injection 

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12.1.2.2 
Screening Period 
(Day -14 to 
Day -1) 
5. Prior to Investigator CR-PCSS or Hexsel 
CSS assessment, subjects will rate each of 
their two buttocks using the PR-PCSS 
while viewing their digital images (section 
13.1.2.1); the Investigator is blinded to 
these scores 
5. Prior to Investigator CR-PCSS assessment, 
subjects will rate each of their two buttocks 
using the PR-PCSS while viewing their 
digital images (section 13.1.2.1); the 
Investigator is blinded to these ratings 
6. After the subject has completed the 
PR-PCSS ratings, the Investigator will 
conduct live assessments of subject’s 
cellulite severity of each of the two 
buttocks using the CR-PCSS (section 
13.1.2.4); the subject is blinded to these 
ratings 
7. After the Investigator has completed the 
CR-PCSS ratings, the Investigator will 
conduct live evaluation of each of the two 
buttocks using the Hexsel CSS; the subject 
is blinded to these ratings. The ratings from 
the PR-PCSS, CR-PCSS, and Hexsel CSS 
(section 13.1.2.6) will be used to assess 
initial eligibility of the buttocks for study 
entry 
6. After the subject has completed the 
PR-PCSS ratings, the Investigator will 
conduct live assessments of subject’s 
cellulite severity of each of the two 
buttocks using the CR-PCSS (section 
13.1.2.5); the subject is blinded to these 
ratings. The ratings from the PR-PCSS and 
CR-PCSS will be used to assess initial 
eligibility of the buttocks for study entry 
12.2 Selecting 
and Marking 
Dimples during 
Treatment Visits 
The cellulite severity assessments using the 
PR-PCSS, CR-PCSS, and Hexsel CSS (note 
that the Hexsel CSS assessment is performed 
at Screening visit and Day 1 visit only) will be 
completed prior to marking dimples and 
injection sites. 
The cellulite severity assessments using the 
PR-PCSS and CR-PCSS, will be completed 
prior to marking dimples and injection sites. 
12.4.1 Treatment 
Visit 1: Pre-
Injection 
4. Subjects will rate each of their buttocks 
using the PR-PCSS (section 13.1.2.1); the 
Investigator is blinded to these scores 
4. Subjects will rate each of their buttocks 
using the PR-PCSS (section 13.1.2.1); the 
Investigator is blinded to these ratings 
Added text 
5. Subjects will complete the Patient 
Reported Cellulite Impact Scale 
assessment (PR-CIS; section 13.1.2.3): the 
Investigator is blinded to this rating 
5. The Investigator will conduct live 
assessments of subject’s cellulite severity 
of each of the buttocks using the CR-PCSS 
(section 13.1.2.4); the subject is blinded to 
these ratings 
6. The Investigator will conduct live cellulite 
evaluation of each of the buttocks using the 
Hexsel CSS. The ratings from the PR-
PCSS, CR-PCSS and Hexsel CSS (section 
13.1.2.6) will be used to assess eligibility 
for randomization 
6. The Investigator will conduct live 
assessments of subject’s cellulite severity 
of each of the buttocks using the CR-PCSS 
(section 13.1.2.5); the subject is blinded to 
these ratings. The ratings from the 
PR-PCSS and CR-PCSS will be used to 
assess eligibility for randomization 

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7. Subjects with PR-PCSS or CR-PCSS 
ratings in either of the buttocks <3 or a 
Hexsel CSS total score in either of the 
buttocks greater than 13 (section 13.1.2.6) 
will be excluded from participation 
7. Subjects with PR-PCSS or CR-PCSS 
ratings in either of the buttocks <3 will be 
excluded from participation 
8. Randomization of subjects with two 
buttocks eligible for treatment (eligible 
criteria being each buttock have PR-PCSS 
and CR-PCSS scores of 3 or 4 and a 
Hexsel CSS total score not greater than 13) 
to treatment (section 12.10); obtain kit 
numbers of study treatment 
8. Randomization of subjects with two 
buttocks eligible for treatment (eligible 
criteria being each buttock have PR-PCSS 
and CR-PCSS scores of 3 or 4) to 
treatment (section 12.10); obtain kit 
numbers of study treatment 
12.6 Day 71 
(+5 days)/End of 
Study/Early 
Termination 
6. Subject Cellulite Assessment of each of the 
two buttocks using the photographic image 
before marking dimples and injection sites 
(NOTE: complete subject cellulite 
assessments before Investigator cellulite 
assessments) using: 
a. Patient Reported Photonumeric Cellulite 
Severity Scale (PR-PCSS) assessment 
(section 13.1.2.1) 
b. Subject Global Aesthetic Improvement 
Scale (S-GAIS) (section 13.1.2.2) 
c. Subject Satisfaction with Cellulite 
Treatment Assessment (section 13.1.2.3); 
note this assessment is of both left and 
right buttocks rather than each individual 
buttock 
6. Subject Cellulite Assessment of each of the 
two buttocks using the photographic image 
before marking dimples and injection sites 
(NOTE: complete subject cellulite 
assessments before Investigator cellulite 
assessments) using: 
a. Patient Reported Photonumeric Cellulite 
Severity Scale (PR-PCSS) assessment 
(section 13.1.2.1) 
b. Subject Global Aesthetic Improvement 
Scale (S-GAIS) (section 13.1.2.2) 
c. Patient Reported Cellulite Impact Scale 
(PR-CIS assessment (section 13.1.2.3); 
note this assessment is of both left and 
right buttocks rather than each individual 
buttock 
d. Subject Satisfaction with Cellulite 
Treatment Assessment (section 13.1.2.4); 
note this assessment is of both left and 
right buttocks rather than each individual 
buttock 
12.10 Blinding 
and 
Randomization 
On Day 1, if each of the buttocks again meet 
the criteria (3 or 4 on the PR-PCSS and 
CR-PCSS and no greater than 13 on Hexsel 
CSS) the subject will be randomized to a 
treatment group. 
On Day 1, if each of the buttocks again meet 
the criteria (3 or 4 on the PR-PCSS and 
CR-PCSS) the subject will be randomized to a 
treatment group. 

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13.1.2.3 Patient 
Reported 
Cellulite Impact 
Scale (PR-CIS) 
Added section 
13.1.2.3. Patient Reported Cellulite Impact 
Scale (PR-CIS) 
At the Day 1 visit and Day 71 visit, subjects 
will be instructed to answer 6 questions related 
to the areas selected for treatment on their 
buttocks on the Patient Reported Cellulite 
Impact Scale (Appendix D) while viewing 
digital images of their buttocks. The PR-CIS 
assesses the visual and emotional impact of 
cellulite (happy, bothered, self-conscious, 
embarrassed, looking older or looking 
overweight or out of shape) using a 6-question 
survey, with each question rated on a 
numerical rating scale from 0 (not at all) to 10 
(extremely). 
This variable will be entered directly into the 
EDC system, thus the electronic database will 
serve as the direct point of data capture and 
will serve as source for this variable. 
13.1.2.4 Subject 
Satisfaction  
Added text 
This variable will be entered directly into the 
EDC system, thus the electronic database will 
serve as the direct point of data capture and 
will serve as source for this variable. 

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13.1.2.6 Hexsel 
Cellulite Severity 
Scale 
13.1.2.6. Hexsel Cellulite Severity Scale 
The Hexsel Cellulite Severity Scale (referred 
to as the Hexsel CSS) is a photonumeric scale 
that looks at 5 key morphologic features of 
cellulite: (A) number of evident depressions, 
(B) depth of depressions, (C) morphological 
appearance of skin surface alterations, (D) 
laxity, flaccidity or sagging of skin, and (E) 
current classification scale based on medical 
literature including Nürnberger and 
Müller.(12,13) Each of these features is 
evaluated on a 4-point scale from a low of 0 to 
a high of 3 as described in Table 8. The total 
score is the summation of all 5 features 
(Appendix D). 
The Investigator or qualified designee will 
independently use the Hexsel CSS to assess 
the severity of EFP in each of the two buttocks 
at the Screening visit and each of the two 
buttocks on Day 1 (Note: In this study, the 
Hexsel CSS is used exclusively for assessment 
of subject eligibility; it is not used as an 
efficacy assessment). All cellulite assessments 
should be made while the subject is in the 
standing position with relaxed gluteus 
muscles. However, when evaluating the 
subject for Category E (classification scale by 
Nürnberger and Müller) (13) if the subject has 
no evident depressions, the subject should be 
asked to contract her gluteus muscles or the 
pinch test should be applied (by pinching the 
skin between the thumb and index finger) so 
the Investigator or qualified designee can 
differentiate between scores/grades of zero (0) 
or I. 
This variable will be entered directly into the 
EDC system, thus the electronic database will 
serve as the direct point of data capture and 
will serve as source for this variable. 
[Table] 
Deleted section and table 
17.5 Efficacy 
Analyses 
All supportive endpoints will be summarized 
as percentages. 
All supportive endpoints will be summarized 
as subject counts and percentages for 
categorical data or n, mean, SD, median, 
minimum, and maximum for continuous data. 
Added text 
Changes in PR-CIS from baselines will be 
analyzed using an analysis of covariance 
(ANCOVA) adjusted for baseline values 

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17.5.3.1 
Supportive 
Variables 
Added text 
• Change from baseline (Day 1) of PR-CIS 
total score at Day 71 
• Change from baseline (Day 1) of 
abbreviated PR-CIS score at Day 71 
• Proportion of subjects with a change from 
baseline (Day 1) of PR-CIS ≥ 12 at Day 71 
• Proportion of subjects with a change from 
baseline (Day 1) of abbreviated PR-CIS ≥ 
10 at Day 71 
19.1 Source 
Documents 
This study allows for direct data entry (DDE) 
for selected data points as outlined below: 
• PR-PCSS 
• CR-PCSS 
• Hexsel CSS 
• S-GAIS 
• I-GAIS 
• Subject Satisfaction with Cellulite 
Treatment Assessment 
This study allows for direct data entry (DDE) 
for selected data points as outlined below: 
• PR-PCSS 
• CR-PCSS 
• S-GAIS 
• I-GAIS 
• PR-CIS 
• Subject Satisfaction with Cellulite 
Treatment Assessment 
27 References 
12. Hexsel DM, Dal’Forno T, Hexsel CL. A 
validated photonumeric cellulite severity 
scale. J Eur Acad Dermatol Venereol. 
2009;23(5):523-8. 
13. Nürnberger F, Müller G. So-called 
cellulite: an invented disease. J Dermatol 
Surg Oncol. 1978;4(3):221-9. 
Deleted text 

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APPENDIX D 
APPENDIX D. HEXSEL DM, DAL’FORNO 
T, HEXSEL CL. A VALIDATED 
PHOTONUMERIC CELLULITE SEVERITY 
SCALE. J EUR ACAD DERMATOL 
VENEREOL. 2009;23(5):523-8 
[Article] 
APPENDIX D. PATIENT REPORTED 
CELLULITE IMPACT SCALE (PR-CIS) 
Please select the rating that best represents 
your answer on a scale of 0 to 10 with 0 
representing “Not at all” and 10 representing 
“Extremely” while viewing digital images of 
your buttocks. Please answer each question. 
1. Thinking about the areas selected for 
treatment, how happy are you with the 
appearance of your cellulite? 
[Scale] 
2. Thinking about the areas selected for 
treatment, how bothered are you by the 
appearance of your cellulite? 
[Scale] 
3. Thinking about the areas selected for 
treatment, how self-conscious are you 
about the appearance of your cellulite? 
[Scale] 
4. Thinking about the areas selected for 
treatment, how embarrassed are you about 
the appearance of your cellulite? 
[Scale] 
5. Thinking about the areas selected for 
treatment, how much older do you look 
because of your cellulite? 
[Scale] 
6. Thinking about the areas selected for 
treatment, how overweight or out of shape 
do you look because of your cellulite? 
[Scale] 
APPENDIX E. 
REFERENCE 
IMAGES FOR 
HEXSEL 
SEVERITY 
RATINGS 
APPENDIX E. REFERENCE IMAGES FOR 
HEXSEL SEVERITY RATINGS  
The 2 images below are representative of a 
Hexsel score of 13, the maximum severity 
level to be included in the study. Subjects with 
cellulite severity that exceeds a Hexsel score 
of 13 should be excluded. 
[Image 1] [Image 2] 
The image below represents a Hexsel score 
>13, and depicts excessive skin laxity in the 
buttock and posterolateral thigh. Subjects with 
a Hexsel score >13 should be excluded from 
the study. 
[Image 3] 
Deleted appendix and images 
 

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4. 
SYNOPSIS 
Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
Title of Study: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of EN3835 in the 
Treatment of Edematous Fibrosclerotic Panniculopathy 
Lead Principal Investigator: 
Study Period:  
Estimated date first subject enrolled:  
Feb-2018 
Estimated date last subject completed:  
Oct-2018 
Phase of Development: 3 
Objectives:  
To assess the efficacy and safety of EN3835 in the treatment of edematous fibrosclerotic panniculopathy 
(EFP), commonly known as cellulite, in adult women  
Study Design: This study is a Phase 3 randomized, double-blind, placebo-controlled study of the 
efficacy and safety of EN3835 in the treatment of EFP in adult women. Subjects will be screened for 
study eligibility within 14 days prior to enrolling in this study. Subjects with 2 treatment areas (bilateral 
buttocks) (also referred to as quadrants) with moderate or severe levels of cellulite as independently 
assessed by the subject using the Patient Reported Photonumeric Cellulite Severity Scale (PR-PCSS) 
and by the Investigator using the Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 
will be eligible. The eligibility of the buttocks will be confirmed on Day 1. 
Once the eligibility of the buttocks is confirmed, subjects will be randomly assigned to a treatment 
group (EN3835 0.84 mg per buttock or placebo) in a 1:1 ratio within an investigational site. Each 
subject will receive a treatment course which consists of up to 3 treatment visits (sessions), separated by 
21 days (ie, Days 1, 22, and 43). Each treatment visit will consist of 12 injections (0.3 mL per injection 
of EN3835 0.07 mg/injection or placebo; 0.84 mg in 3.6 mL per buttock) in each of the two buttocks for 
a total volume of 7.2 mL (1.68 mg). Selection of dimples to be treated in the buttocks will be at the 
discretion of the Investigator. End of study will occur at study day 71. Of the two assigned eligible 
buttocks, one buttock will be randomly selected as the target buttock for the primary efficacy endpoint. 
The other (remaining) buttock will be considered the non-target buttock. Subjects, investigators, site 
personnel, and Endo personnel will be blinded to the identification of the target and non-target buttocks. 
At each treatment visit, each of the buttocks will be photographed before and after marking dimples and 
injection sites while the subject is in a consistent, standardized relaxed standing pose. The subject will 
assess the digital photographic image (pre-marking) of each of the buttocks using the PR-PCSS to 
determine the severity of EFP in each of the buttocks. In addition, the subject will evaluate each of the 
buttocks using a Subject Global Aesthetic Improvement Scale (S-GAIS). Subsequently, the Investigator 
will conduct live assessments of each buttock using the CR-PCSS. At Day 1, the subject will complete a 
Patient Reported Cellulite Impact Scale (PR-CIS) assessment and a Subject Self-Rating Scale (SSRS) 
assessment. The subject assessments will always be completed prior to and independently of the 
Investigator assessments at each treatment visit. In addition, the Investigator will assess each of the 
buttocks using an Investigator Global Aesthetic Improvement Scale (I-GAIS). All of the assessments 
must be done before the dimple marking. 
At Day 71 (End of Study/Early Termination), photographs of each of the buttocks will be taken and 
evaluated by subject using the PR-PCSS. The Investigator will conduct live assessments of each of the 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
buttocks using the CR-PCSS. Global assessment evaluations will be completed by both the subject and 
the Investigator. 
Number of Subjects (Planned): 420 
Study Center(s): Approximately 25 sites in United States 
Diagnosis and Inclusion/Exclusion Criteria: 
Inclusion Criteria: 
1. Voluntarily sign and date an informed consent agreement 
2. Be a female ≥18 years of age 
3. At Screening visit, have 2 bilateral buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as reported by the Investigator (CR-PCSS) 
4. At Day 1 visit, have 2 bilateral buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as reported by the Investigator (CR-PCSS) 
5. Be willing to apply sunscreen to the buttocks before each exposure to the sun while participating 
in the study (ie, Screening through end of study) 
6. Be judged to be in good health, based upon the results of a medical history, physical 
examination, and laboratory profile at Screening  
7. Have a negative serum pregnancy test at Screening and a negative urine pregnancy test before 
injection of study drug and be using a stable and effective contraception method (eg, abstinence, 
intrauterine device [IUD], hormonal [estrogen/progestin] contraceptives, or double barrier 
method) for at least 1 menstrual cycle prior to study enrollment and for the duration of the 
study; or be menopausal defined as 12 months of amenorrhea in the absence of other biological 
or physiological causes, as determined by the Investigator; or post-menopausal for at least 
1 year; or be surgically sterile  
8. Be willing and able to cooperate with the requirements of the study 
9. Be able to read, complete and understand the patient-reported outcomes rating instruments in 
English 
Exclusion Criteria: 
A subject will be excluded from study participation if she: 
1. Has any of the following systemic conditions: 
a. Coagulation disorder 
b. Evidence or history of malignancy (other than excised basal-cell carcinoma) unless there 
has been no recurrence in at least 5 years 
c. History of keloidal scarring or abnormal wound healing 
d. Concurrent diseases or conditions that might interfere with the conduct of the study, 
confound the interpretation of the study results, or endanger the subject’s well-being. Any 
questions about concurrent diseases should be discussed with the Medical Monitor 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
e. Evidence of clinically significant abnormalities on physical examination, vital signs, 
electrocardiogram (ECG), or clinical laboratory values  
2. Has any of the following local conditions in the areas to be treated: 
a. History of lower extremity thrombosis or post-thrombosis syndrome 
b. Vascular disorder (eg, varicose veins, telangiectasia) in area to be treated 
c. Inflammation or active infection 
d. Severe skin laxity, flaccidity, and/or sagging  
e. Active cutaneous alteration including rash, eczema, psoriasis, or skin cancer 
f. Has a tattoo and/or a mole located within 2 cm of the site of injection  
3. Requires the following concomitant medications before or during participation in the trial: 
a. Anticoagulant or antiplatelet medication or has received anticoagulant or antiplatelet 
medication (except for ≤150 mg aspirin daily) within 7 days before injection of study drug 
4. Has used any of the following for the treatment of EFP on a buttock within the timelines 
identified below or intends to use any of the following at any time during the course of the 
study: 
a. Liposuction in a buttock during the 12-month period before injection of study drug 
b. Injections (eg, mesotherapy); radiofrequency device treatments; laser treatment; buttock 
implant treatment; cryolipolysis; or surgery (including subcision and/or powered subcision) 
within a buttock during the 12-month period before injection of study drug 
c. Any investigational treatment for EFP on a buttock during the 12-month period before 
injection of study drug 
d. Endermologie™ or similar treatments within a buttock during the 6-month period before 
injection of study drug 
e. Massage therapy within a buttock during the 3-month period before injection of study drug 
f. Creams (eg, Celluvera™, TriLastin®) and/or home therapies to prevent or mitigate EFP 
within a buttock during the 2-week period before injection of study drug 
5. Is presently nursing or providing breast milk 
6. Intends to become pregnant during the study 
7. Intends to initiate an intensive sport or exercise program during the study 
8. Intends to initiate a weight reduction program during the study 
9. Intends to use tanning spray or tanning booths during the study 
10. Has received an investigational drug or treatment within 30 days before injection of study drug 
11. Has a known systemic allergy to collagenase or any other excipient of study drug 
12. Has received any collagenase treatments at any time prior to treatment 
13. Was a subject in a previous cellulite clinical trial of collagenase clostridium histolyticum 
(CCH): AUX-CC-830, AUX-CC-831, EN3835-102, EN3835-104, EN3835-201, EN3835-202, 
and/or EN3835-205 
14. Any other condition(s) that, in the Investigator’s opinion, might indicate the subject to be 
unsuitable for the study 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
Investigational Product, Dosage and Mode of Administration: EN3835, 1.68 mg, subcutaneous. A 
dose of 0.84 mg of EN3835 per buttock will be administered as 12 subcutaneous injections (0.3-mL 
injection administered as three 0.1-mL aliquots per injection) in each of two buttocks for a total dose of 
1.68 mg and a total volume of 7.2 mL (3.6 mL per buttock). Total number of injections will be 
24 injections per treatment visit into the two buttocks. There will be 3 treatment visits at 21 days 
intervals, ie, treatments on Days 1, 22, and 43 will be administered. 
Duration of Study: Approximately 84 days (includes screening phase) 
Screening Phase: Up to 14 days 
Criteria for Evaluation: 
Efficacy: 
• 
Subject using PR-PCSS while viewing digital image of the target buttock: 5-level scale 
ranging from 0 (no cellulite) to 4 (severe cellulite) (Day 1 (Baseline) and Days 22, 43, and 
71) for the target buttock 
• 
Subject using PR-PCSS while viewing digital image of the non-target buttock: 5-level scale 
ranging from 0 (no cellulite) to 4 (severe cellulite) (Day 1 (Baseline) and Days 22, 43, and 
71) for the non-target buttock 
• 
Investigator using the CR-PCSS by live assessment: 5-level scale ranging from 0 (no 
cellulite) to 4 (severe cellulite) (Day 1 (Baseline) and Days 22, 43, and 71) for the target 
buttock 
• 
Investigator using the CR-PCSS by live assessment: 5-level scale ranging from 0 (no 
cellulite) to 4 (severe cellulite) (Day 1 (Baseline) and Days 22, 43, and 71) for the 
non-target buttock 
• 
Investigator Global Aesthetic Improvement Scale (I-GAIS): 7-level scale ranging from 3 
(very much improved) to −3 (very much worse) (Days 22, 43, and 71) for the target buttock 
• 
Investigator Global Aesthetic Improvement Scale (I-GAIS): 7-level scale ranging from 3 
(very much improved) to −3 (very much worse) (Days 22, 43, and 71) for the non-target 
buttock 
• 
Subject Global Aesthetic Improvement Scale (S-GAIS): 7-level scale ranging from 3 (very 
much improved) to −3 (very much worse) (Days 22, 43, and 71) for the target buttock 
• 
Subject Global Aesthetic Improvement Scale (S-GAIS): 7-level scale ranging from 3 (very 
much improved) to −3 (very much worse) (Days 22, 43, and 71) for the non-target buttock 
• 
Patient Reported Cellulite Impact Scale (PR-CIS): 6 questions with responses to each 
question consisting of a numerical rating scale (NRS) ranging from 0 (Not at all) to 
10 (Extremely) 
• 
Subject Self-Rating Scale (SSRS): 7-level scale ranging from 0 (extremely dissatisfied) to 6 
(extremely satisfied) (Day 1 (Baseline) and Day 71) 
• 
Subject satisfaction with cellulite treatment assessment: 5-level scale ranging from 2 (very 
satisfied) to −2 (very dissatisfied) (Day 71) for both the target and non-target buttocks 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
• 
Safety population: The Safety population is defined as all subjects who have received at 
least 1 injection of study medication. 
• 
Per-Protocol population: The Per-Protocol population is defined as those mITT subjects 
who do not have any major protocol deviations. 
Analyses:  
Analyses of Primary Endpoint: 
The primary endpoint is the proportion of 2-level composite responders at Day 71 defined as subjects 
with: 
• 
an improvement in severity from baseline (Day 1 visit) of at least 2 levels of severity in the 
CR-PCSS as assessed live by the Investigator of the target buttock, and 
• 
an improvement in severity from baseline of at least 2 levels of severity in the PR-PCSS as 
assessed by the subject while viewing the digital image of the target buttock. 
A subject will be considered a responder if these criteria are met in the randomized target buttock of that 
subject. 
The primary endpoint will be summarized as percentages and analyzed using a Cochran-Mantel-
Haenszel test that compares the 2 treatment groups and adjusts for Investigator at a level of significance 
of 0.05. The ITT population will be evaluated for the primary endpoint with any subject not having an 
evaluation of CR-PCSS and/or PR-PCSS at Day 71 classified as a non-responder. 
Sensitivity analyses for the primary endpoint will include: 
• 
ITT subjects with missing data handled by multiple imputation (MI) approach 
• 
ITT subjects with missing data handled by a last observation carried forward (LOCF) 
approach 
• 
mITT subjects with missing data handled by an LOCF approach 
• 
Observed data only (no missing data imputed) 
• 
Per-protocol (PP) subjects with missing data handled by an LOCF approach if 10% or more 
subjects are excluded in the PP population from mITT population. 
Analyses of Key Secondary Endpoints:  
There will be 8 key secondary endpoints grouped as three families of 2 to 4 endpoints per family 
analyzed in hierarchical order. 
• 
Family #1 – four endpoints: 
- 
Proportion of 1-level PR-PCSS responders defined as subjects with ≥1-level 
improvement in PR-PCSS severity rating of the target buttock at Day 71 compared to 
Day 1 
- 
Proportion of 2-level PR-PCSS responders defined as subjects with ≥2-level 
improvement in PR-PCSS severity rating of target buttock at Day 71 compared to Day 1 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
- 
Proportion of 1-level composite responders of target buttock (defined as subjects with an 
improvement in severity from baseline of at least 1 level of severity in the CR-PCSS of 
the target buttock assessed live by the Investigator and an improvement of severity from 
baseline of at least 1 level of severity in the PR-PCSS of the target buttock) at Day 71 
compared to Day 1 
- 
Proportion of 2-level composite responders of the non-target buttock at Day 71 compared 
to Day 1 
• 
Family #2 – two endpoints: 
- 
Proportion of 1-level SSRS responders defined as subjects who were at least slightly 
satisfied at Day 71 (SSRS rating ≥ 4)  
- 
Change from baseline (Day 1) of the PR-CIS total score at Day 71 
• 
Family #3 – two endpoints: 
- 
Proportion of 1-level S-GAIS responders defined as subjects with ≥1-level improvement 
(improved, much improved or very much improved) in the S-GAIS assessment of the 
target buttock at Day 71 
- 
Proportion of 2-level S-GAIS responders defined as subjects with ≥2-level improvement 
(much improved or very much improved) in the S-GAIS assessment of the target buttock 
at Day 71 
The key secondary efficacy analyses will be analyzed in the same manner as the primary endpoint based 
on the ITT population. The family #1 key secondary efficacy analyses will be performed only if the 
primary efficacy analysis is significant at a significance level of p ≤ 0.05 (gatekeeping strategy). 
Similarly, family #2 key secondary efficacy analyses will be performed only if at least one of the key 
secondary efficacy endpoints of family #1 is significant at a significance level of p ≤ 0.0125 and 
family #3 key secondary efficacy analyses will be performed only if at least one of the key secondary 
efficacy endpoints of family #2 is significant (parallel gatekeeping strategy). Within a family of key 
secondary efficacy endpoints, the Bonferroni method will be performed to relocate unused alpha for 
testing each endpoint to assure an overall error rate of p ≤ 0.05. The details of the testing procedures will 
be provided in the statistical analysis plan for the study. 
Supportive Endpoints: 
The supportive variables will evaluate assessments at various study time points and using various 
populations.  
• 
Proportion of 2-level PR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 2 levels of severity in the PR-PCSS) of the target buttock 
(Days 22, 43, and 71) 
• 
Proportion of 2-level PR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 2 levels of severity in the PR-PCSS) of the non-target 
buttock (Days 22, 43, and 71) 
• 
Proportion of 1-level PR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 1 level of severity in the PR-PCSS) of the target buttock 
(Days 22, 43, and 71) 

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Page 41 
 
 
 
Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
• 
Proportion of 1-level PR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 1 level of severity in the PR-PCSS) of the non-target 
buttock (Days 22, 43, and 71) 
• 
Proportion of 2-level PR-PCSS responders of at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if this criterion is met in the target buttock or 
non-target buttock or both buttocks in that subject. 
• 
Proportion of 1-level PR-PCSS responders of at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if this criterion is met in the target buttock or 
non-target buttock or both buttocks in that subject.  
• 
Proportion of 2-level PR-PCSS responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both the 
target and non-target buttocks. 
• 
Proportion of 1-level PR-PCSS responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both the 
target and non-target buttocks. 
• 
Proportion of 2-level CR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 2 levels of severity in the CR-PCSS) of the target buttock 
(Days 22, 43, and 71)  
• 
Proportion of 2-level CR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 2 levels of severity in the CR-PCSS) of the non-target 
buttock (Days 22, 43, and 71) 
• 
Proportion of 1-level CR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 1 level of severity in the CR-PCSS) of the target buttock 
(Days 22, 43, and 71) 
• 
Proportion of 1-level CR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 1 level of severity in the CR-PCSS) of the non-target 
buttock (Days 22, 43, and 71) 
• 
Proportion of 2-level CR-PCSS responders of at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if this criterion is met in the target buttock or 
non-target buttock or both buttocks in that subject 
• 
Proportion of 1-level CR-PCSS responders of at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if this criterion is met in the target buttock or 
non-target buttock or both buttocks in that subject 
• 
Proportion of 2-level CR-PCSS responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both the 
target and non-target buttocks 
• 
Proportion of 1-level CR-PCSS responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both the 
target and non-target buttocks 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
• 
Proportion of 1-level composite responders of the target buttock (defined as subjects with an 
improvement in severity from baseline of at least 1 level of severity in the CR-PCSS of the 
target buttock assessed live by the Investigator and an improvement of severity from 
baseline of at least 1 level of severity in the PR-PCSS of that same target buttock) (Days 22, 
43, and 71) 
• 
Proportion of 1-level composite responders of the non-target buttock (defined as subjects 
with an improvement in severity from baseline of at least 1 level of severity in the CR-PCSS 
of the non-target buttock assessed live by the Investigator and an improvement of severity 
from baseline of at least 1 level of severity in the PR-PCSS of that same non-target buttock) 
(Days 22, 43, and 71) 
• 
Proportion of 1-level composite responders of at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if this criterion is met in the target buttock or 
non-target buttock or both buttocks in that subject. 
• 
Proportion of 1-level composite responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both the 
target and non-target buttocks. 
• 
Proportion of 2-level composite responders of the target buttock (defined as subjects with an 
improvement in severity from baseline of at least 2 levels of severity in the CR-PCSS of the 
target buttock assessed live by the Investigator and an improvement of severity from 
baseline of at least 2 levels of severity in the PR-PCSS of that same target buttock) 
(Days 22, 43, and 71) 
• 
Proportion of 2-level composite responders of the non-target buttock (defined as subjects 
with an improvement in severity from baseline of at least 2 levels of severity in the 
CR-PCSS of the non-target buttock assessed live by the Investigator and an improvement of 
severity from baseline of at least 2 levels of severity in the PR-PCSS of that same non-target 
buttock) (Days 22, 43, and 71) 
• 
Proportion of 2-level composite responders of at least one of two buttocks (Days 22, 43, 
and 71). A subject will be considered a responder if this criterion is met in the target buttock 
or non-target buttock or both buttocks in that subject.  
• 
Proportion of 2-level composite responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both the 
target and non-target buttocks. 
• 
Proportion of subjects at each level of the S-GAIS of the target buttock (Days 22, 43, and 
71) 
• 
Proportion of subjects at each level of the S-GAIS of the non-target buttock (Days 22, 43, 
and 71) 
• 
Proportion of 1-level S-GAIS responders defined as subjects with a response of at least 1 
(improved) in the S-GAIS of the target buttock (Days 22, 43, and 71) 
• 
Proportion of 1-level S-GAIS responders defined as subjects with a response of at least 1 
(improved) in the S-GAIS of the non-target buttock (Days 22, 43, and 71) 

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Page 43 
 
 
 
Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
• 
Proportion 1-level S-GAIS responders of at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if this criterion is met in the target buttock or 
non-target buttock or both buttocks in that subject. 
• 
Proportion of 1-level S-GAIS responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both the 
target and non-target buttocks. 
• 
Proportion of subjects at each level of the I-GAIS of the target buttock (Days 22, 43, and 
71) 
• 
Proportion of subjects at each level of the I-GAIS of the non-target buttock (Days 22, 43, 
and 71) 
• 
Proportion of 1-level I-GAIS responders defined as subjects with a response of at least 1 
(improved) in the I-GAIS of the target buttock (Days 22, 43, and 71) 
• 
Proportion of I-level S-GAIS responders defined as subjects with a response of at least 1 
(improved) in the I-GAIS of the non-target buttock (Days 22, 43, and 71) 
• 
Proportion of 1-level I-GAIS responders of at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if this criterion is met in the target buttock or 
non-target buttock or both buttocks in that subject.  
• 
Proportion of 1-level I-GAIS responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both the 
target and non-target buttocks. 
• 
Change from baseline (Day 1) of the PR-CIS score at Day 71 
• 
Change from baseline (Day 1) of the abbreviated PR-CIS score at Day 71 
• 
Proportion of subjects with a change from baseline (Day1) of the PR-CIS ≥12 at Day 71 
• 
Proportion of subjects with a change from baseline (Day 1) of the abbreviated PR-CIS ≥10 
at Day 71 
• 
Proportion of subjects at each level of the subject self-rating scale (SSRS) (Day 1 (Baseline) 
and Day 71 
• 
Proportion of 1-level SSRS responders defined as subjects who were at least slightly 
satisfied at Day 71 (SSRS rating ≥ 4) 
• 
Proportion of subjects at each level of the subject satisfaction with cellulite treatment 
assessment (Day 71) 
• 
Proportion of satisfied responders (defined as subjects with a response of at least 1 
(ie, 1-Satisfied or 2-Very Satisfied) in the subject satisfaction with cellulite treatment 
assessment (Day 71) 
All supportive endpoints will be summarized as percentages. The dichotomous secondary endpoints 
(ie, responder endpoints) will be analyzed using a Cochran-Mantel-Haenszel test adjusted for 
Investigator. Changes in the PR-PCSS ratings and CR-PCSS ratings from baselines, S-GAIS scores, and 
I-GAIS scores will be analyzed using the Mann-Whitney test. 

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Page 44 
 
 
 
Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
Safety Analysis: 
The following variables are safety endpoints: 
• 
AEs: Mapped to preferred term using the Medical Dictionary for Regulatory Activities 
(MedDRA) 
• 
Vital signs 
• 
Clinical laboratory tests 
AEs will be summarized by proportion of subjects reporting each event. The Fisher exact test will be 
used to compare EN3835 to placebo. Descriptive statistics will be presented for actual and change from 
baseline at each visit for vital signs and for each clinical laboratory test parameter. The comparison 
between treatment groups will be based on the change from baseline for clinical laboratory tests and 
vital signs using an analysis of variance (ANOVA) with a factor of drug (EN3835 or placebo). 
Immunogenicity: Anti-AUX-I and anti-AUX-II antibody levels will be summarized using descriptive 
statistics for the actual value at the visit. Samples from Day 1, Day 22, Day 43, and Day 71 visits will be 
analyzed for anti-AUX-I and anti-AUX-II antibodies and a subset of Day 1 and Day 71 samples will be 
analyzed for neutralizing antibodies. 
 

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5. 
SCHEDULE OF EVENTS 
Procedures 
Day -14 to -1 
 
Screening 
Day 1 
Treatment  
Visit 1 
Day 22 (± 3 d) 
Treatment  
Visit 2 
Day 43 (± 3 d) 
Treatment  
Visit 3 
Day 71 (+ 5 d) / 
End of Study / 
Early Termination 
Unscheduled 
Clinic Visita 
Informed consent 
X 
 
 
 
 
 
Inclusion/exclusion 
X 
 
 
 
 
 
Digital photography 
X 
Xb 
Xb 
Xb 
X 
X 
Medical history/EFP history including previous 
treatments 
X 
 
 
 
 
 
Prior/concomitant medications/procedures 
X 
X 
X 
X 
X 
X 
Physical examination: 
X 
 
 
 
 
 
• Body weight 
X 
 
Xc 
Xc 
X 
X 
• Height  
X 
 
 
 
 
 
• Fitzpatrick skin type 
X 
 
 
 
 
 
Vital signs 
X 
Xd 
Xd 
Xd 
X 
X 
12-lead ECG 
X 
 
 
 
 
 
Collection of samples: 
• Clinical laboratory 
X 
 
 
 
X 
X 
• Anti-AUX-I/anti-AUX-II antibody level 
 
Xc 
Xc 
Xc 
X 
 
• Pregnancy testing 
Xe 
Xc,e 
Xc,e 
Xc,e 
Xe 
X 
Subject cellulite assessmentsf: 
• Patient Reported Photonumeric Cellulite 
Severity Scale (PR-PCSS) 
Xg,h 
Xc,g,h 
Xc,g,h 
Xc,g,h 
Xg,h 
 
• Subject Global Aesthetic Improvement 
(S-GAIS) 
 
 
Xc,g,h 
Xc,g,h 
Xg,h 
 
• Patient Reported Cellulite Impact Scale 
(PR-CIS) 
 
Xc,g 
 
 
Xg 
 
• Subject Satisfaction With Cellulite Treatment 
Assessment 
 
 
 
 
Xg 
 
• Subject Self-Rating Scale (SSRS) 
 
Xc 
 
 
X 
 

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Page 46 
 
 
 
Procedures 
Day -14 to -1 
 
Screening 
Day 1 
Treatment  
Visit 1 
Day 22 (± 3 d) 
Treatment  
Visit 2 
Day 43 (± 3 d) 
Treatment  
Visit 3 
Day 71 (+ 5 d) / 
End of Study / 
Early Termination 
Unscheduled 
Clinic Visita 
Investigator cellulite assessments: 
• Selection of dimples to be treated within the 
two buttocks 
 
Xc 
Xc 
Xc 
 
 
• Marking the dimples and injection sites to be 
treated within the buttocks 
 
Xc 
Xc 
Xc 
 
 
• Clinician Reported Photonumeric Cellulite 
Severity Scale (CR-PCSS) 
X 
Xc,h 
Xc,h 
Xc,h 
Xh 
 
• Investigator Global Aesthetic Improvement 
(I-GAIS)  
 
 
Xc,h 
Xc,h 
Xc,h 
 
Confirm eligibility 
 
Xc 
 
 
 
 
Randomize to treatment 
 
Xc,i 
 
 
 
 
Study drug administration 
 
X 
X 
X 
 
 
Injection site reactions/local tolerability in the 
buttocks 
 
X 
X 
X 
X 
X 
Adverse events 
Monitored Throughout Study 
a During unscheduled visits, the Investigator or designee may perform any study procedure that they deem clinically necessary (eg, vital signs, clinical lab assessments, and 
pregnancy test). 
b Before and after marking the dimples and injection sites. 
c Before injection. 
d Up to 4 hours before injection; approximately 15 and 30 minutes after injection. Vital signs must be stable before the subject is discharged. 
e Serum pregnancy test on Screening visit and Day 71/EOS visit; urine pregnancy test on Day 1, Day 22, and Day 43 visits. 
f Subject assessments should be completed independently and prior to Investigator assessments at each visit. 
g Assessment made via photographs (if treatment visit, use photographs taken before marking dimples and injection sites). 
h Assessment of each of the 2 buttocks independently. 
i Before randomization, each of the subject’s buttocks must have ratings of 3 or 4 (moderate or severe) in both the CR-PCSS and PR-PCSS. 
NOTE: Subject cellulite assessments must be completed before the Investigator cellulite assessments are conducted at each visit.  
d=Days; ECG=Electrocardiogram; EFP=Edematous fibrosclerotic panniculopathy; EOS=End of study 

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Page 47 
 
 
 
6. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES 
TABLE OF CONTENTS 
1. 
TITLE PAGE ................................................................................................................1 
2. 
SUMMARY OF CHANGES ........................................................................................2 
3. 
SPONSOR CONTACT INFORMATION .................................................................33 
4. 
SYNOPSIS .................................................................................................................34 
5. 
SCHEDULE OF EVENTS .........................................................................................45 
6. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............47 
7. 
LIST OF ABBREVIATIONS.....................................................................................53 
8. 
INTRODUCTION ......................................................................................................54 
8.1. 
Background .................................................................................................................54 
8.1.1. 
Edematous Fibrosclerotic Panniculopathy .................................................................54 
8.1.2. 
Current EFP Treatments .............................................................................................54 
8.1.3. 
EN3835 (Collagenase Clostridium Histolyticum) ......................................................55 
8.2. 
Summary of Nonclinical Studies ................................................................................56 
8.3. 
Summary of Known Risks and Benefits .....................................................................56 
8.4. 
Rationale .....................................................................................................................57 
9. 
OBJECTIVES .............................................................................................................58 
9.1. 
Primary Objective .......................................................................................................58 
9.2. 
Secondary Objectives .................................................................................................58 
9.3. 
Exploratory Objectives ...............................................................................................58 
10. 
INVESTIGATIONAL PLAN .....................................................................................59 
10.1. 
Study Design ...............................................................................................................59 
10.2. 
Selection of Doses ......................................................................................................59 
10.3. 
Study Drug Administration.........................................................................................60 
10.4. 
Care Procedures After Injection .................................................................................62 
10.5. 
Discussion of Study Design, Including the Choice of Control Groups ......................62 
11. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................63 
11.1. 
Subject Inclusion Criteria ...........................................................................................63 
11.2. 
Subject Exclusion Criteria ..........................................................................................63 
11.3. 
Subject Discontinuation Criteria .................................................................................65 

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11.3.1. 
Replacement Procedures .............................................................................................65 
12. 
TREATMENT OF SUBJECTS ..................................................................................66 
12.1. 
Study Visits .................................................................................................................66 
12.1.1. 
Informed Consent .......................................................................................................66 
12.1.2. 
Subject Screening .......................................................................................................66 
12.1.2.1. 
Medical History ..........................................................................................................66 
12.1.2.2. 
Screening Period (Day -14 to Day -1) ........................................................................66 
12.2. 
Selecting and Marking Dimples during Treatment Visits ..........................................67 
12.3. 
Digital Photography during Treatment Visits 1, 2, and 3 ...........................................68 
12.4. 
Treatment Visit 1 (Day 1) ...........................................................................................69 
12.4.1. 
Treatment Visit 1: Pre-Injection .................................................................................69 
12.4.2. 
Treatment Visit 1: Injection and Post-injection ..........................................................70 
12.5. 
Treatment Visit 2 (Day 22 [±3 days]) and Treatment Visit 3 (Day 43 
[±3 days]) ....................................................................................................................70 
12.5.1. 
Treatment Visits 2 and 3: Pre-injection ......................................................................70 
12.5.2. 
Treatment Visits 2 and 3: Injection and Post-injection ..............................................71 
12.6. 
Day 71 (+5 days) / End of Study / Early Termination ................................................71 
12.7. 
Unscheduled Visits .....................................................................................................72 
12.8. 
Prior and Concomitant Medications and Procedures ..................................................72 
12.8.1. 
Prohibited Medications or Procedures ........................................................................72 
12.9. 
Treatment Compliance ................................................................................................72 
12.10. 
Blinding and Randomization ......................................................................................72 
13. 
ASSESSMENT OF EFFICACY ................................................................................74 
13.1. 
Efficacy Measurements ..............................................................................................74 
13.1.1. 
Digital Photography ....................................................................................................74 
13.1.2. 
Subject and Investigator Cellulite Assessments .........................................................74 
13.1.2.1. 
Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) ........................74 
13.1.2.2. 
Subject Global Aesthetic Improvement Scale (S-GAIS)............................................75 
13.1.2.3. 
Patient Reported Cellulite Impact Scale (PR-CIS) .....................................................76 
13.1.2.4. 
Subject Satisfaction with Cellulite Treatment Assessment ........................................76 
13.1.2.5. 
Subject Self-Rating Scale (SSRS) ..............................................................................77 
13.1.2.6. 
Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) ....................77 
13.1.2.7. 
Investigator Global Aesthetic Improvement Scale (I-GAIS) .....................................78 

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14. 
ASSESSMENT OF SAFETY .....................................................................................79 
14.1. 
Definitions ..................................................................................................................79 
14.1.1. 
Adverse Events ...........................................................................................................79 
14.1.2. 
Serious Adverse Events ..............................................................................................79 
14.2. 
Monitoring Adverse Events ........................................................................................80 
14.3. 
Relationship to Study Drug ........................................................................................80 
14.4. 
Intensity Assessment ..................................................................................................81 
14.5. 
Reporting Adverse Events and Serious Adverse Events ............................................81 
14.5.1. 
Reporting Adverse Events ..........................................................................................81 
14.5.2. 
Reporting Serious Adverse Events .............................................................................81 
14.5.2.1. 
Follow-up Procedures for Serious Adverse Events ....................................................82 
14.6. 
Special Reporting Situations .......................................................................................82 
14.6.1. 
Adverse Events of Special Interest .............................................................................82 
14.6.2. 
Overdose/Misuse/Abuse .............................................................................................82 
14.6.2.1. 
Overdose .....................................................................................................................82 
14.6.3. 
Pregnancy ...................................................................................................................83 
14.6.4. 
AEs/SAEs Experienced by Non-subjects Exposed to Study Medication ...................83 
14.7. 
Clinical Laboratory Determinations ...........................................................................83 
14.8. 
Anti-AUX-I and Anti-AUX-II Antibodies .................................................................85 
14.9. 
Vital Signs ..................................................................................................................85 
14.10. 
Electrocardiogram .......................................................................................................85 
14.11. 
Physical Examination .................................................................................................86 
14.12. 
Other Safety Assessments ...........................................................................................86 
15. 
ASSESSMENT OF PHARMACOKINETICS ...........................................................87 
16. 
ASSESSMENT OF PHARMACODYNAMICS ........................................................88 
17. 
STATISTICAL CONSIDERATIONS AND METHODS .........................................89 
17.1. 
Determination of Sample Size ....................................................................................89 
17.2. 
Subject Populations ....................................................................................................90 
17.2.1. 
Safety Population ........................................................................................................90 
17.2.2. 
Intent-to-Treat (ITT) Population .................................................................................90 
17.2.3. 
Modified Intent-to-Treat (mITT) Population ..............................................................90 
17.2.4. 
Per-Protocol (PP) Population ......................................................................................90 
17.3. 
Subject Disposition .....................................................................................................90 

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17.4. 
Demographics and Other Baseline Characteristics .....................................................91 
17.5. 
Efficacy Analyses .......................................................................................................91 
17.5.1. 
Primary Efficacy Variable ..........................................................................................92 
17.5.2. 
Secondary Efficacy Variables .....................................................................................92 
17.5.2.1. 
Key Secondary Variables ...........................................................................................92 
17.5.3. 
Supportive Efficacy Variables ....................................................................................93 
17.5.3.1. 
Supportive Variables ..................................................................................................93 
17.6. 
Safety Analyses ..........................................................................................................96 
17.6.1. 
Prior, Concomitant, and Follow-up Medication .........................................................97 
17.6.2. 
Study Drug Exposure ..................................................................................................97 
17.6.3. 
Measurement of Treatment Compliance ....................................................................97 
17.6.4. 
Adverse Events ...........................................................................................................97 
17.6.5. 
Vital Signs ..................................................................................................................98 
17.6.6. 
Clinical Laboratory Parameters ..................................................................................98 
17.6.7. 
Electrocardiogram .......................................................................................................98 
17.6.8. 
Physical Examination .................................................................................................99 
17.6.9. 
Other Safety Measurements ........................................................................................99 
17.7. 
Pharmacokinetic Analyses ..........................................................................................99 
17.8. 
Pharmacodynamic Analyses .......................................................................................99 
17.9. 
Other Data (eg, Health Economics/QOL, Pharmacogenetic, etc) ..............................99 
17.10. 
Interim Analysis ..........................................................................................................99 
17.11. 
Statistical Software .....................................................................................................99 
18. 
STUDY DRUG MATERIALS AND MANAGEMENT .........................................100 
18.1. 
Study Drug Identity ..................................................................................................100 
18.2. 
Study Drug Packaging and Labeling ........................................................................100 
18.3. 
Study Drug Storage ...................................................................................................100 
18.4. 
Study Drug Preparation ............................................................................................100 
18.5. 
Study Drug Accountability .......................................................................................101 
18.5.1. 
Study Drug Handling and Disposal ..........................................................................101 
19. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS.......................................102 
19.1. 
Source Documents ....................................................................................................102 
19.2. 
Study Monitoring ......................................................................................................102 
19.3. 
Audits and Inspections ..............................................................................................102 

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19.4. 
Institutional Review Board (IRB) .............................................................................102 
19.5. 
Data Recording and Documentation .........................................................................103 
20. 
QUALITY CONTROL AND QUALITY ASSURANCE .......................................104 
21. 
ETHICS ....................................................................................................................105 
21.1. 
Ethics Review ...........................................................................................................105 
21.2. 
Ethical Conduct of the Study ....................................................................................105 
21.3. 
Subject Information and Consent .............................................................................106 
22. 
DATA HANDLING AND RECORDKEEPING .....................................................107 
22.1. 
Data Collection .........................................................................................................107 
22.2. 
Study Documentation ...............................................................................................107 
23. 
REPORTING AND PUBLICATION .......................................................................108 
24. 
INVESTIGATOR OBLIGATIONS .........................................................................109 
24.1. 
Regulatory Documents .............................................................................................109 
24.2. 
Delegation of Responsibilities and Adequate Resources .........................................110 
24.3. 
Medical Care of Study Subjects ...............................................................................110 
24.4. 
Use of Investigational Materials ...............................................................................110 
24.5. 
Retention of Records ................................................................................................110 
24.6. 
Subject Confidentiality .............................................................................................111 
25. 
TERMINATION OF STUDY ..................................................................................112 
26. 
INVESTIGATOR’S STATEMENT .........................................................................113 
27. 
REFERENCES .........................................................................................................114 
APPENDIX A. DOCUMENTS REQUIRED PRIOR TO INITIATION OF THE 
STUDY .....................................................................................................................115 
APPENDIX B. PATIENT-REPORTED PHOTONUMERIC CELLULITE SEVERITY 
SCALE (PR-PCSS) FOR THE BUTTOCK .............................................................117 
APPENDIX C. CLINICIAN-REPORTED PHOTONUMERIC CELLULITE 
SEVERITY SCALE (CR-PCSS) FOR THE BUTTOCK ........................................118 
APPENDIX D. PATIENT REPORTED CELLULITE IMPACT SCALE (PR-CIS) ..............119 
 

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LIST OF TABLES 
Table 1: 
Sponsor Contact Information ......................................................................................33 
Table 2: 
Abbreviations and Special Terms ...............................................................................53 
Table 3: 
Study Treatment Groups .............................................................................................59 
Table 4: 
Concomitant Medication Restrictions for Subjects during the Treatment 
Phase of Study ............................................................................................................72 
Table 5: 
Subject Global Aesthetic Improvement Scale (S-GAIS)............................................76 
Table 6: 
Subject Satisfaction with Cellulite Treatment Assessment - Buttocks .......................76 
Table 7: 
Subject Self-Rating Scale (SSRS) ..............................................................................77 
Table 8: 
Investigator Global Aesthetic Improvement Scale (I-GAIS) .....................................78 
Table 9: 
Clinical Laboratory Tests ...........................................................................................84 
Table 10: Vital Signs Measurements on Injection Day ..............................................................85 
Table 11: Fitzpatrick Scale .........................................................................................................86 
Table 12: Previous Results as Basis for Sample Size .................................................................89 
 
LIST OF FIGURES 
Figure 1: 
Study Design ...............................................................................................................59 
Figure 2: 
Study Drug Administration at Each Injection Site .....................................................61 
 
 

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7. 
LIST OF ABBREVIATIONS  
The following abbreviations and specialized terms are used in this study protocol. 
Table 2: 
Abbreviations and Special Terms 
Abbreviation 
Definition 
AE 
Adverse event 
AUX-I 
Clostridial class I collagenase 
AUX-II 
Clostridial class II collagenase 
BMI 
Body mass index 
CR-PCSS 
Clinician Reported Photonumeric Cellulite Severity Scale 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
EFP 
Edematous fibrosclerotic panniculopathy 
ePRO 
Electronic patient reported outcome 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HREC 
Human Research Ethics Committee 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
I-GAIS 
Investigator-Global Aesthetic Improvement Scale 
IRB 
Institutional Review Board 
ITT 
Intent-to-treat 
IWRS 
Interactive web response system 
LOCF 
Last observation carried forward 
MI 
Multiple imputation 
mITT 
Modified intent-to-treat 
PR-CIS 
Patient Reported Cellulite Impact Scale 
PR-PCSS 
Patient Reported Photonumeric Cellulite Severity Scale 
Quadrant 
A quadrant is a treatment area 
Qualified designee 
Qualified by education and training to perform the study procedure (eg, 
sub-Investigator, nurse). 
SAE 
Serious adverse event 
S-GAIS 
Subject – Global Aesthetic Improvement Scale 
SSRS 
Subject Self-Rating Scale 
TEAE 
Treatment-emergent adverse event. Adverse events that occur on or after the 
first injection of study drug. 

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8. 
INTRODUCTION 
8.1. 
Background 
8.1.1. 
Edematous Fibrosclerotic Panniculopathy 
Edematous fibrosclerotic panniculopathy (EFP), commonly known as cellulite, has been defined 
as a local metabolic disorder of subcutaneous tissues that results in a contour abnormality of the 
skin.(1) The condition manifests as dimpled skin, particularly in the gluteal-femoral region.(2,3) 
EFP is caused by herniation of subcutaneous fat lobules through the dermohypodermal junction 
and/or shortening of the collagen septa that cross the hypodermal layer and connects the dermis 
to the underlying fascia. This creates an uneven surface with dimpling.(1,2) EFP is a medical 
condition resulting in a potentially cosmetically unacceptable alteration of the skin, and affects 
an estimated 85% to 98% of postpubertal women.(1,3) 
The pathophysiology of EFP is not completely understood, but there are 3 main theories: edema 
resulting from excessive hydrophilia of the intercellular matrix, alteration of the regional 
microcirculation, and different anatomical conformation of collagenous subcutaneous tissues in 
women versus men.(4) 
It is known that EFP is different from generalized obesity. In generalized obesity, adipocytes 
undergo hypertrophy and hyperplasia that are not limited to the pelvis, thighs, and abdomen.(1) 
In areas of EFP, adipocytes have physiologic and biochemical properties that differ from adipose 
tissue located elsewhere. Large, metabolically-stable adipocytes characterize EFP-prone areas; 
thus, the responsiveness to catecholamine-induced lipolysis is less in EFP tissues compared to 
visceral fat, which has the greatest responsiveness.(1) 
Subcutaneous fat lobes are separated from one another by thin, usually rigid strands of 
collagenous connective tissues, which cross the fatty layers and connect the dermis to the 
underlying fascia. These septa stabilize the subcutis and divide the fat. In EFP, shortening of the 
collagen septa due to fibrosis provokes retraction at the insertion points of the trabeculae, 
causing the depressions that characterize EFP.(2) There are a higher percentage of thinner, 
perpendicular hypodermal septa in women with EFP than in men.(1) Weight gain makes EFP 
more noticeable, but it may be present even in thin subjects. Genetics may also play a role since 
EFP tends to run in families. 
8.1.2. 
Current EFP Treatments 
There are therapies that have been utilized in an attempt to treat cellulite; however, there are no 
approved pharmacologic treatments. Despite multiple therapeutic modalities, there is little 
scientific evidence that any of these treatments are beneficial. In fact, much of the evidence is 
anecdotal, subjective, or based only on patient self-assessment.(5) Some of the historical 
treatments for EFP have included weight loss,(6) topical agents,(5) massage,(7) liposuction,(5,6) 
mesotherapy,(6) radiofrequency,(6) subcision and powered subcision,(8) and laser 
therapies;(9,10) some of these treatments may pose an increased risk for adverse effects.(5) 

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There remains an unmet medical need for safe and effective therapies to improve the aesthetic 
outcome in women with cellulite. To effectively treat cellulite, a therapeutic approach may 
require disruption of the dermal septa, which are composed of collagen and cause the skin 
dimpling that is bothersome to many women. 
8.1.3. 
EN3835 (Collagenase Clostridium Histolyticum) 
Endo Pharmaceuticals Inc. (Endo) is developing EN3835 for the treatment of EFP. Because 
EN3835 is a proteinase that can hydrolyze the triple-helical region of collagen under 
physiological conditions, EN3835 has the potential to be effective in lysing subdermal collagen, 
such as those observed in the dermal septa, which are the underlying cause of the skin dimpling 
in women with EFP. EN3835 targets the collagenase structural matrix (eg, dermal septa) at the 
site of injection and does not require systemic exposure to be effective. 
EN3835 is a parenteral lyophilized product comprised of 2 collagenases in an approximate 1:1 
mass ratio, Collagenase I (AUX-I, Clostridial class I collagenase) and Collagenase II (AUX-II; 
Clostridial class II collagenase). These collagenases are isolated and purified from the 
fermentation of Clostridium histolyticum. 
Collagenase AUX-I is a single polypeptide chain containing approximately 1,000 amino acids of 
known sequence and with a molecular weight of 114 kDa. Collagenase AUX-II is also 
approximately 1,000 amino acids long and has a molecular weight of 113 kDa. These 
2 collagenases are not immunologically cross-reactive and have different specificities, such that 
together they become synergistic, providing a very broad hydrolyzing reactivity toward collagen. 
Clostridial collagenases are proteinases that can hydrolyze the triple-helical region of collagen 
under physiological conditions. 
EN3835 is currently approved (brand name is XIAFLEX®) for: 1) the treatment of adults with 
Dupuytren’s contracture with a palpable cord and, 2) for the treatment of adult men with 
Peyronie’s disease with a palpable plaque and curvature deformity of at least 30° at the start of 
therapy. 
A recent Phase 2b, randomized, double-blind, placebo-controlled study (EN3835-201) of 
375 women randomized to treatment of one treatment area (quadrant) (quadrant was defined in 
study EN3835-201 as a left buttock, a right buttock, a left posterolateral thigh or a right 
posterolateral thigh) of cellulite with EN3835 0.84 mg or placebo in a 1:1 ratio assessed the 
effectiveness and safety of EN3835. Efficacy in this study was evaluated based on cellulite 
assessments using Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS), Patient 
Reported Photonumeric Cellulite Severity Scale (PR-PCSS), Investigator Global Aesthetic 
Improvement Scale (GAIS-I), Subject Global Aesthetic Improvement Scale (GAIS-S), and 
Subject Satisfaction with Cellulite Treatment. 
Results from the Phase 2b study demonstrated that treatment (3 visits approximately 21 days 
apart) improved the cellulite severity of the treatment area as assessed by the primary endpoint of 
2-level composite responder analyses, the proportion of responders based on an improvement of 
≥2 levels in the appearance of cellulite in both the patient PR-PCSS and the clinician CR-PCSS 
of buttocks and thighs was statistically significantly greater in subjects who received EN3835 
0.84 mg (10.6%; p<0.001) compared to subjects who received placebo (1.6%); 1-level (or 
greater) responders in the PR-PCSS of EN3835-treated subjects (72.3%) was significantly 

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greater than 1-level responders in the placebo group (51.6%) (p<0.001); statistically significant 
(p≤0.001) improvement in the appearance of cellulite based on the subject S-GAIS were 
observed in EN3835 0.84-mg group (73.1%) compared to the placebo group (44.0%); and 62.9% 
of subjects in the EN3835 0.84 mg group were satisfied or very satisfied with the results of their 
cellulite treatment compared with only 35.9% of subjects in the placebo group (p<0.001). In 
subjects treated in buttocks (n=187), the proportion of 2-level composite responders was 
statistically significantly greater in subjects who received EN3835 0.84 mg (14.9%; p<0.001) 
compared to subjects who received placebo (1.1%); 1-level (or greater) responders in the 
PR-PCSS of EN3835-treated subjects (72.7%) was significantly greater than 1-level responders 
in the placebo group (47.8%) (p<0.001). 
The study also demonstrated EN3835 to be well tolerated with no serious adverse events (SAEs) 
related to EN3835. Safety results from a total of 4 studies (1 pilot, 2 Phase 1, and 2 Phase 2 
studies) in which 435 adult females received subcutaneous injections of EN3835 indicate that the 
majority of treatment-emergent adverse events (TEAEs) are transient, non-serious, mild or 
moderate in intensity, and related to the local administration of EN3835. The immunogenicity 
profile after 3 treatment visits of EN3835 indicate that greater than 90% of EN3835-treated 
subjects were seropositive for AUX-I and/or AUX-II antibodies; this profile of EN3835 is 
similar to that observed in the Dupuytren’s contracture and Peyronie’s disease programs. 
A Phase 1, open-label safety and pharmacokinetic study of a single dose of EN3835 0.84 mg in 
11 female subjects with EFP showed that there was no quantifiable levels of AUX-I or AUX-II 
at any time point after subcutaneous injection of EN3835 0.84 mg into one quadrant. A second 
Phase 1, open-label safety and pharmacokinetic study of a single dose of EN3835 0.84 mg per 
treatment area in two treatment areas (buttock-buttock, thigh-thigh, or buttock-thigh) 
concurrently (total dose of 1.68 mg) showed that there was no quantifiable levels of AUX-I or 
AUX-II at any time point post-dose attributable to the injection of EN3835 1.68 mg. 
The results from these studies suggest that subcutaneous injections of EN3835 in the area of 
cellulite may be a well-tolerated and effective medical treatment for adults with EFP. 
8.2. 
Summary of Nonclinical Studies 
Non-clinical studies necessary to support clinical studies have been performed and are 
summarized in the Investigator Brochure (IB).(11) Non-clinical studies in the following areas 
were performed: toxicology, reprotoxicity, genotoxicity, and hypersensitivity. 
8.3. 
Summary of Known Risks and Benefits 
A summary of safety risks is provided in the IB.(11) The following events have been commonly 
observed: local injection site reactions (injection site bruising, injection site swelling, injection 
site pain) for the various approved indications as well as those being investigated. In the phase 
2b study of EN3835 in women with EFP, the following treatment related adverse events ≥2% of 
189 EN3835-treated women were reported: injection site bruising (75.1%), injection site pain 
(59.3%), injection site nodule (14.3%), injection site pruritus (11.1%), injection site swelling 
(7.4%), injection site induration (5.8%), injection site mass (5.3%), injection site discolouration 
(3.2%), and injection site erythema (2.1%). These events are similar to events reported in the 
clinical trials of EN3835 for the approved indications. Postmarketing safety data are consistent 
with safety data reported in clinical trials. 

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Although a thorough benefit of EN3835 has not been fully evaluated in the treatment of EFP, the 
efficacy results from the Phase 2b study and previous EFP studies warranted further 
development. 
8.4. 
Rationale 
The results from the Phase 2b EFP study (EN3835-201) further suggested that EN3835 0.84 mg 
per treatment area (quadrant) is an effective treatment of EFP based on improvement in the 
severity of cellulite as determined by the Investigator and the subject. There were no safety 
concerns following 0.84 mg per treatment area in the treatment of EFP (section 8.1.3). Safety 
findings from the Phase 2b EFP study are similar to that observed in previous clinical studies 
with EN3835 in the treatment of EFP and XIAFLEX in the treatment of Dupuytren’s contracture 
and Peyronie’s disease, in that that the majority of AEs occurred at the site of injection and 
resolved before the next scheduled treatment. The immunogenicity profile of EN3835 in the 
Phase 2b EFP study is similar in previous studies and programs. 
Based on the efficacy and safety findings from the Phase 2a and 2b EFP studies, the EN3835 
0.84-mg dose per treatment area in two treatment areas (buttocks) warranted further investigation 
in this study. 
Treating two buttocks at each treatment visit will potentially provide a symmetrical-like 
improvement in appearance. Support for evaluation of the treatment of two buttocks concurrently 
is based on: 1) the safety findings from the previous EFP studies are local to the injection site, 
2) the pharmacological activity of EN3835 is local and does not require systemic exposure, and 
3) no significant quantifiable systemic concentration has been attributable to injection of two 
buttocks concurrently. 
The integration of dose and use justification supports this study of evaluation of EN3835 
0.84 mg per treatment area in two treatment areas (buttocks) concurrently. 
 

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9. 
OBJECTIVES 
9.1. 
Primary Objective 
The primary objective of this study is to assess the efficacy and safety of EN3835 in the 
treatment of edematous fibrosclerotic panniculopathy (EFP) commonly known as cellulite in 
adult women. 
9.2. 
Secondary Objectives 
There are no secondary objectives of this study. 
9.3. 
Exploratory Objectives 
There are no exploratory objectives of this study. 
 

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10. 
INVESTIGATIONAL PLAN 
10.1. 
Study Design 
This study will be performed at approximately 25 study centers located in the United States. This 
clinical study will be conducted as a multicenter, randomized, double-blind, placebo-controlled 
study comparing EN3835 to placebo in adult women with EFP. The study will consist of 71 days 
of double-blind treatment. Subjects meeting the entry criteria for this study will be randomized to 
EN3835 treatment or placebo treatment in a 1:1 ratio within an investigational site.  
The complete Schedule of Events is provided in section 5. 
Figure 1: 
Study Design 
 
Table 3: 
Study Treatment Groups 
Dose per 
Each Injectiona / 
Number of 
Subjects 
Injection 
Volume per 
Each Injection 
Number of 
Injections at Each 
Treatment Visit 
Dose (mg) at Each 
Treatment Visit 
Injection Volume 
(mL) per Each 
Treatment Visit 
Cumulative  
EFP Dose 
EN3835 0.07 mg / 
N=210 
0.3 mL 
12 per buttock  
× 2 buttocks =  
24 injections 
0.84 mg per buttock  
× 2 buttocks = 
1.68 mg 
(12 injections  
per buttock ×  
0.07 mg/injection ×  
2 buttocks) 
3.6 mL per buttock  
× 2 buttocks = 
7.2 mL  
(24 injections × 
0.3 mL) 
5.04 mg 
(3 treatment visits × 
0.84 mg per buttock 
× 2 buttocks) 
Placebo /  
N=210 
0.3 mL 
12 per buttock  
× 2 buttocks =  
24 injections 
- 
3.6 mL per buttock  
× 2 buttocks = 
7.2 mL  
(24 injections × 
0.3 mL) 
- 
a Each injection of study drug is 0.3 mL administered as three 0.1 mL aliquots. 
10.2. 
Selection of Doses 
The dose of EN3835 chosen for this study was based on the results from earlier studies. 
The data from the Phase 2a EFP dose-ranging study (AUX-CC-831) suggest that EN3835 
0.84 mg is most effective in the treatment of EFP based on improvement in the severity of 

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cellulite as determined by both the Investigator and the subject, although the EN3835 0.48-mg 
group did show improvement in some of the efficacy parameters. 
• There were no safety concerns following administration of up to 3 treatment visits of 
EN3835 0.84 mg in the treatment of EFP (AUX-CC-831 CSR). The safety profile of 
EN3835 0.84 mg in the treatment of EFP was similar to that observed in the EN3835 
0.06-mg group and the EN3835 0.48-mg group. No notable differences were 
observed across the 3 treatment groups. 
• Safety findings from the Phase 2a EFP dose-ranging study are similar to that 
observed in previous clinical studies with XIAFLEX in the treatment of Dupuytren’s 
contracture and Peyronie’s disease, in that the majority of AEs occurred at the site of 
injection and resolved before the next scheduled treatment. 
• The immunogenicity profile of EN3835 in the Phase 2a EFP dose-ranging study is 
similar to that observed in the Dupuytren’s contracture and Peyronie’s disease 
programs. 
• Based on the efficacy and safety findings from the Phase 2a EFP dose-ranging study, 
the EN3835 0.84-mg dose was carried forward to the Phase 2b study. 
The results from the Phase 2b EFP study (EN3835-201) further suggested that EN3835 0.84 mg 
is an effective treatment of EFP based on improvement in the severity of cellulite as determined 
by the Investigator and the subject. There were no safety concerns following EN3835 0.84 mg 
in the treatment of EFP (section 8.4). Safety findings from the Phase 2b EFP study are similar to 
that observed in previous clinical studies with XIAFLEX in the treatment of Dupuytren’s 
contracture and Peyronie’s disease, in that that the majority of AEs occurred at the site of 
injection and resolved before the next scheduled treatment. The immunogenicity profile of 
EN3835 in the Phase 2b EFP study is similar to that observed in the Dupuytren’s contracture 
and Peyronie’s disease programs. 
Based on the efficacy and safety findings from the Phase 2a and 2b EFP studies, the EN3835 
0.84-mg dose per treatment area was carried forward to this study. The findings from previous 
studies that the majority of adverse events after EN3835 treatment are local to the injection site 
and that there is no quantifiable systemic exposure observed after concurrent treatment of two 
buttocks (total dose of 1.68 mg) supports the proposed study to evaluate EN3835 treatment of 
two buttocks. 
10.3. 
Study Drug Administration 
Study drug will be injected subcutaneously while the subject is in a prone position using a 
syringe with a 30-gauge ½-inch needle. Each injection site will receive a single skin injection of 
study drug administered as three 0.1-mL aliquots to Positions A, B, and C (for a total injection 
volume of 0.3 mL) as shown in the following figure. The depth of injection corresponds to the 
length of the treatment needle (0.5 inches) from the tip of the needle to the hub or base of the 
needle without downward pressure. 
During each treatment visit, 8 syringes (4 syringes per buttock) will be prepared for dosing. Each 
syringe will contain 0.9 mL of study drug (ie, 3 injections in each syringe). Twelve (12) skin 

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10.4. 
Care Procedures After Injection 
To evaluate the subject for possible immediate immunological AEs, the subject will remain in 
direct observation of medical personnel who are skilled in the management of an allergic 
reaction for 30 minutes after receiving the injections of study drug and until the subject exhibits 
no sign of an immunological or other clinically significant systemic or local AE. The subject’s 
vital signs should be stable before the subject can leave direct observation (see section 14.9). 
The Investigator or qualified designee will then apply a sterile dressing to the injection areas 
with hypoallergenic tape. The subject will be instructed to remove the dressing in the evening. 
10.5. 
Discussion of Study Design, Including the Choice of Control Groups 
The design of this study was based on the primary objective to evaluate the efficacy and safety of 
EN3835 0.84 mg per buttock in the concurrent treatment (total dose of 1.68 mg) of 2 bilateral 
buttocks with EFP in adult women compared with placebo treatment. The study design, a 
multi-center, double-blind, placebo-controlled study is in accordance with regulatory guidelines 
of adequate and well-controlled clinical studies (Food and Drug Administration [FDA] Guidance 
for Industry: Providing Clinical Evidence of Effectiveness for Human Drug and Biological 
Products, 1998.; ICH E8 and E10). 
 

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11. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
11.1. 
Subject Inclusion Criteria 
In order to be eligible to participate in the study, subjects must meet the following criteria: 
1. Voluntarily sign and date an informed consent agreement 
2. Be a female ≥18 years of age 
3. At Screening visit, have 2 bilateral buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as reported by the Investigator (CR-PCSS) 
4. At Day 1 visit, have 2 bilateral buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as reported by the Investigator (CR-PCSS) 
5. Be willing to apply sunscreen to the buttocks before each exposure to the sun while 
participating in the study (ie, Screening through end of study) 
6. Be judged to be in good health, based upon the results of a medical history, physical 
examination, and laboratory profile at Screening 
7. Have a negative serum pregnancy test at Screening and a negative urine pregnancy test 
before injection of study drug and be using a stable and effective contraception method 
(eg, abstinence, intrauterine device [IUD], hormonal [estrogen/progestin] contraceptives, 
or double barrier method) for at least 1 menstrual cycle prior to study enrollment and for 
the duration of the study; or be menopausal defined as 12 months of amenorrhea in the 
absence of other biological or physiological causes, as determined by the Investigator; or 
post-menopausal for at least 1 year; or be surgically sterile 
8. Be willing and able to cooperate with the requirements of the study 
9. Be able to read, complete and understand the patient-reported outcomes rating 
instruments in English 
11.2. 
Subject Exclusion Criteria 
Subjects who meet any of the following criteria will not be eligible to participate in the study: 
1. Has any of the following systemic conditions: 
a. Coagulation disorder 
b. Evidence or history of malignancy (other than excised basal-cell carcinoma) unless 
there has been no recurrence in at least 5 years 
c. History of keloidal scarring or abnormal wound healing 
d. Concurrent diseases or conditions that might interfere with the conduct of the study, 
confound the interpretation of the study results, or endanger the subject’s well-being. 

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Any questions about concurrent diseases should be discussed with the Medical 
Monitor 
e. Evidence of clinically significant abnormalities on physical examination, vital signs, 
electrocardiogram (ECG), or clinical laboratory values 
2. Has any of the following local conditions in the areas to be treated: 
a. History of lower extremity thrombosis or post-thrombosis syndrome 
b. Vascular disorder (eg, varicose veins, telangiectasia) in area to be treated 
c. Inflammation or active infection 
d. Severe skin laxity, flaccidity, and/or sagging 
e. Active cutaneous alteration including rash, eczema, psoriasis, or skin cancer 
f. Has a tattoo and/or a mole located within 2 cm of the site of injection 
3. Requires the following concomitant medications before or during participation in the 
trial: 
a. Anticoagulant or antiplatelet medication or has received anticoagulant or antiplatelet 
medication (except for ≤150 mg aspirin daily) within 7 days before injection of study 
drug 
4. Has used any of the following for the treatment of EFP on a buttock within the timelines 
identified below or intends to use any of the following at any time during the course of 
the study: 
a. Liposuction in a buttock during the 12-month period before injection of study drug 
b. Injections (eg, mesotherapy); radiofrequency device treatments; laser treatment; 
buttock implant treatment; cryolipolysis; or surgery (including subcision and/or 
powered subcision) within a buttock during the 12-month period before injection of 
study drug 
c. Any investigational treatment for EFP on a buttock during the 12-month period 
before the injection of study drug 
d. Endermologie or similar treatments within a buttock during the 6-month period 
before injection of study drug 
e. Massage therapy within a buttock during the 3-month period before injection of study 
drug 
f. Creams (eg, Celluvera™, TriLastin®) and/or home therapies to prevent or mitigate 
EFP within a buttock during the 2-week period before injection of study drug 
5. Is presently nursing or providing breast milk  
6. Intends to become pregnant during the study 
7. Intends to initiate an intensive sport or exercise program during the study 
8. Intends to initiate a weight reduction program during the study 
9. Intends to use tanning spray or tanning booths during the study 

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10. Has received an investigational drug or treatment within 30 days before injection of study 
drug 
11. Has a known systemic allergy to collagenase or any other excipient of study drug 
12. Has received any collagenase treatments at any time prior to treatment 
13. Was a subject in a previous cellulite clinical trial of CCH: AUX-CC-830, AUX-CC-831, 
EN3835-102, EN3835-104, EN3835-201, EN3835-202, and/or EN3835-205 
14. Any other condition(s) that, in the Investigator’s opinion, might indicate the subject to be 
unsuitable for the study  
11.3. 
Subject Discontinuation Criteria 
A premature discontinuation will occur when a subject who signed informed consent ceases 
participation in the study, regardless of circumstances, prior to the completion of the protocol. 
Subjects can be prematurely discontinued from the study for one of the following reasons: 
• An adverse event 
• Lack of efficacy 
• A protocol violation (reason must be specified, for example: lack of compliance, use 
of a prohibited concomitant medication, failure to meet inclusion/exclusion criteria 
after study entry, etc) 
• Withdrawal by subject (reason must be specified) 
• The subject was “lost to follow-up” 
• Other reasons (reason must be specified, for example: the subject moved, pregnancy, 
Investigator decision, Sponsor decision to terminate trial, etc) 
If a subject discontinues from the study, all end-of-study procedures including safety and 
efficacy assessments should be conducted as detailed in the Schedule of Events (section 5). The 
date a subject discontinues and the reason for discontinuation will be recorded in the source 
documentation and electronic case report form (eCRF). If, however, a subject withdraws consent, 
no end-of-study procedures and assessments are required (but are encouraged to reduce missing 
information) except the collection of adverse event (AE) information. This information should be 
recorded in the source documentation and the eCRF. 
11.3.1. 
Replacement Procedures 
Subjects who discontinue from the study will not be replaced. 

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12. 
TREATMENT OF SUBJECTS 
12.1. 
Study Visits 
The Schedule of Events to be performed at each visit is shown in section 5. Provided below are 
further details where additional instruction about the assessments that will be performed is 
deemed to be needed. 
12.1.1. 
Informed Consent 
Signed and dated informed consent will be obtained from each subject before any study 
procedures are undertaken, or before any changes to the subject’s medication regimen are made. 
Details about how the informed consent will be obtained and documented are provided in 
section 21.3, Subject Information and Consent. 
12.1.2. 
Subject Screening 
Investigators will be expected to maintain a Screening log of all potential study subjects. This log 
will include limited information about the potential subject and the date and outcome of the 
screening process (eg, enrolled into the study, reason for ineligibility, or refused to participate). 
Investigators will provide information about the study to subjects who appear to meet the criteria 
for participation in the study. The screening log will be captured directly by the electronic data 
capture (EDC) system. 
12.1.2.1. Medical History 
During the screening period, the Investigator or qualified designee will obtain a medical history 
from each subject that includes relevant diagnoses and/or procedures/therapies with 
onset/resolutions dates. Medical histories should also include history of EFP (start date and 
family history), and history of tobacco and alcohol use (never, current, former). 
12.1.2.2. Screening Period (Day -14 to Day -1) 
Subjects meeting the relevant eligibility criteria listed in section 11 may be enrolled in the study 
after the nature and purpose of the protocol have been explained and written informed consent to 
participate has been voluntarily provided by the subject or their legally authorized representative. 
The subject identification number will consist of 8 digits. The first 4 digits represent the study 
site number followed by a 4-digit subject number. 
The following procedures will be performed and documented during the screening period: 
1. Obtain written informed consent (section 12.1.1) 
2. Evaluate eligibility based on inclusion/exclusion criteria (section 11.1 and section 11.2) 
3. Subject will have digital photographs taken of her two buttocks (section 13.1.1) 
4. Subjects will get instruction on the use of the PR-PCSS (section 13.1.2.1) 

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5. Prior to Investigator CR-PCSS assessment, subjects will rate each of their two buttocks 
using the PR-PCSS while viewing their digital images (section 13.1.2.1); the Investigator 
is blinded to these ratings 
6. After the subject has completed the PR-PCSS ratings, the Investigator will conduct live 
assessments of subject’s cellulite severity of each of the two buttocks using the CR-PCSS 
(section 13.1.2.6); the subject is blinded to these ratings. The ratings from the PR-PCSS 
and CR-PCSS will be used to assess initial eligibility of the buttocks for study entry 
7. Medical history including EFP history (section 12.1.2.1) 
8. Record prior and concomitant medications/procedures (section 12.8) 
9. Physical examination including measurement of body weight, height, Fitzpatrick skin 
type (section 14.11) 
10. Vital sign measurements (section 14.9) 
11. 12-lead ECG (section 14.10) 
12. Collection of samples for: 
a. Clinical laboratory testing (section 14.7) 
b. Serum pregnancy testing (section 14.7) 
13. Adverse events (section 14) 
12.2. 
Selecting and Marking Dimples during Treatment Visits 
Selection of dimples to be treated in the two buttocks is at the discretion of the Investigator. 
Dimples must be well-defined and evident when the subject is standing in a consistent, 
standardized relaxed pose (without the use of any manipulation such as skin pinching or muscle 
contraction). Each subject will receive 3 treatment visits of study drug according to 
randomization unless the buttock is dimple-free (score of 0 on CR-PCSS as reported by the 
Investigator) at Treatment Visit 2 and/or Treatment Visit 3 (a dimple -free buttock at Treatment 
Visit 1 is precluded by the eligibility criteria); a dimple-free buttock at Treatment Visit 2 and/or 
Treatment Visit 3 does not preclude treatment of the contralateral buttock unless it is dimple-free 
also. During each treatment visit, each of the buttocks will be photographed before and after 
marking dimples and injection sites while the subject is standing in a consistent, standardized 
relaxed pose as described in the Photography Manual. The cellulite severity assessments using 
the PR-PCSS and CR-PCSS will be completed prior to marking dimples and injection sites. 
The Investigator or qualified designee will select dimples within each buttock that are well-
defined, evident when the subject is standing, and suitable for treatment; treatment consists of 
12 injections per buttock (24 injections total in two buttocks) per treatment visit. Because the 
goal of treatment is to improve the aesthetic appearance of each entire buttock, the Investigator 
will be instructed to select dimples that in his or her opinion would most improve the aesthetic 
appearance of each entire buttock. The same dimples within a buttock or different dimples within 
a buttock may be treated at each treatment visit but injections must all be within the buttocks 
(12 injections per buttock) for all 3 visits. Each buttock will receive all 3 treatment visits unless 
the buttock has no treatable EFP dimples and the Investigator rates the buttock a score of 0 on 
the CR-PCSS. If no injections in a particular buttock (right or left) are given at Treatment 

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Visit 2, subjects will still be assessed for treatment in the contralateral buttock at Treatment 
Visit 2, and will return for the Day 43 visit and each of the buttocks will again be evaluated by 
the subject (PR-PCSS) and Investigator (CR-PCSS). If the Investigator rates either or both of the 
buttocks greater than 0 on the CR-PCSS, injections at Treatment Visit 3 should be given. 
For each dimple selected for treatment, the Investigator or qualified designee will choose 
injection sites (injection sites within a dimple should be spaced approximately 2 cm apart, if a 
dimple requires more than 1 injection; locating at least one injection site at the nadir, if present, 
of the dimple). Each injection site will be marked with a “dot” using a surgical marker. For 
round dimples, the “dot” will be placed in the center of the dimple; for elongated dimples, “dots” 
will be spaced out approximately 2 cm along the longer axis of the dimple. The Investigator or 
qualified designee will then use a surgical marker to circle each of the dimples selected for 
treatment. Circles in the buttock should not overlap. 
Each of the buttocks will be photographed before and after marking dimples and injection sites 
while the subject is standing in a consistent, standardized relaxed pose as described in the 
Photography Manual. 
Examples of subject dimple and injection site markings are shown as follows: 
Sample Buttock Marking 
 
12.3. 
Digital Photography during Treatment Visits 1, 2, and 3 
During each treatment visit, each of the two buttocks will be photographed before and after 
marking dimples and injections sites while the subject is standing in a consistent, standardized 
relaxed pose as described in section 13.1.1. 

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12.4. 
Treatment Visit 1 (Day 1) 
12.4.1. 
Treatment Visit 1: Pre-Injection 
1. Confirm eligibility criteria 
2. Take digital photography of each of the buttocks before marking dimples and injection 
sites (section 13.1.1) 
3. Subjects will get instruction on the use of the PR-PCSS (Patient Instructions for Use of 
PR-PCSS) 
4. Subjects will rate each of their buttocks using the PR-PCSS (section 13.1.2.1); the 
Investigator is blinded to these ratings 
5. Subjects will complete the Patient Reported Cellulite Impact Scale assessment (PR-CIS; 
section 13.1.2.3): the Investigator is blinded to this rating 
6. Subjects will complete the Subject Self-Rating Scale (SSRS) assessment 
(section 13.1.2.5); the Investigator is blinded to these ratings 
7. The Investigator will conduct live assessments of subject’s cellulite severity of each of 
the buttocks using the CR-PCSS (section 13.1.2.6); the subject is blinded to these ratings. 
The ratings from the PR-PCSS and CR-PCSS will be used to assess eligibility for 
randomization 
8. Subjects with PR-PCSS or CR-PCSS ratings in either of the buttocks <3 will be excluded 
from participation 
9. Upon confirmation of two buttocks eligible for treatment (eligible criteria being each 
buttock have PR-PCSS and CR-PCSS scores of 3 or 4), the IWRS system will randomly 
assign one buttock as the target buttock in the background. Subjects, investigators, site 
personnel and Endo personnel will be blinded to target buttock assignment. 
10. Randomization of subjects with two buttocks eligible for treatment (eligible criteria being 
each buttock have PR-PCSS and CR-PCSS scores of 3 or 4) to treatment (section 12.10); 
obtain kit numbers of study treatment. Subjects, investigators, site personnel, and Endo 
personnel will be blinded to treatment assignment. 
11. Record concomitant medications/procedures (section 12.8) 
12. Vital sign measurements (section 14.9) 
13. Collection of samples for: 
a. Anti-AUX-I and anti-AUX-II antibody testing (section 14.8) 
b. Urine pregnancy testing (section 14.7) 
14. Select and mark dimples to be treated in each of the buttocks (section 12.2) 
15. Take digital photograph of each of the buttocks after marking dimples and injection sites 
(section 13.1.1) 

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12.4.2. 
Treatment Visit 1: Injection and Post-injection 
1. Administration of study drug in the prone position (section 10.3) 
2. Record number of dimples treated and number of injections administered in each of the 
two buttocks 
3. Vital sign measurements (section 14.9) 
4. Injection site reactions and local tolerability 
5. Adverse events (section 14) 
12.5. 
Treatment Visit 2 (Day 22 [±3 days]) and Treatment Visit 3 (Day 43 
[±3 days]) 
12.5.1. 
Treatment Visits 2 and 3: Pre-injection 
1. Record concomitant medications/procedures (section 12.8) 
2. Body weight measurements 
3. Vital sign measurements (section 14.9) 
4. Collection of samples for: 
a. Anti-AUX-I and anti-AUX-II antibody testing (section 14.8) 
b. Urine pregnancy testing (section 14.7) 
5. Digital photographs of each of the two buttocks before marking dimples and injection 
sites (section 13.1.1) 
6. Subject Cellulite Assessments of each of the buttocks using the photographic image of 
each buttock before marking dimples and injection sites (NOTE: complete subject 
cellulite assessments before Investigator cellulite assessments) in the following sequential 
order using: 
a. Patient Reported Photonumeric Cellulite Severity Scale (PR-PCSS) assessment 
(section 13.1.2.1); complete this prior to conducting S-GAIS  
b. Subject Global Aesthetic Improvement Scale (S-GAIS) (section 13.1.2.2) 
7. Investigator Cellulite Assessments live of each of the buttocks in the following sequential 
order prior to marking dimples and injection sites using: 
a. Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) live assessment 
of subject (section 13.1.2.6) 
b. Investigator Global Aesthetic Improvement Scale (I-GAIS) (section 13.1.2.7) 
8. Select and mark dimples to be treated in each buttock (section 12.2) 
9. Digital photographs of each buttock after marking dimples and injection sites 
(section 13.1.1)  
10. For eligible buttock(s), obtain kit number(s) of study treatment 

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12.5.2. 
Treatment Visits 2 and 3: Injection and Post-injection 
1. Administration of study drug in the prone position (section 10.3) 
2. Record number of dimples treated and number of injections administered in each buttock 
3. Vital sign measurements (section 14.9) 
4. Injection site reactions and local tolerability 
5. Adverse events (section 14) 
12.6. 
Day 71 (+5 days) / End of Study / Early Termination 
The following procedures will be performed on Day 71: 
1. Record concomitant medications/procedures (section 12.8) 
2. Measurement of body weight 
3. Vital sign measurements (section 14.9) 
4. Collection of samples for: 
a. Clinical laboratory testing (section 14.7) 
b. Serum pregnancy test (section 14.7) 
c. Anti-AUX-I and anti-AUX-II antibody testing (section 14.8) 
5. Digital photographs of each of the buttocks 
6. Subject Cellulite Assessment of each of the two buttocks using the photographic image 
before marking dimples and injection sites (NOTE: complete subject cellulite 
assessments before Investigator cellulite assessments) using: 
a. Patient Reported Photonumeric Cellulite Severity Scale (PR-PCSS) assessment 
(section 13.1.2.1) 
b. Subject Global Aesthetic Improvement Scale (S-GAIS) (section 13.1.2.2) 
c. Patient Reported Cellulite Impact Scale (PR-CIS) assessment (section 13.1.2.3); note 
this assessment is of both left and right buttocks rather than each individual buttock 
d. Subject Satisfaction with Cellulite Treatment Assessment (section 13.1.2.4); note this 
assessment is of both left and right buttocks rather than each individual buttock 
e. Subject Self-Rating Scale (SSRS) assessment (section 13.1.2.5); note this assessment 
is of both left and right buttocks rather than each individual buttock 
7. Investigator Cellulite Assessments of each of the buttocks live using: 
a. Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) live assessment 
of subject (section 13.1.2.6) 
b. Investigator Global Aesthetic Improvement Scale (I-GAIS) (section 13.1.2.7) 
8. Injection site reactions and local tolerability 
9. Adverse events (section 14) 

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12.7. 
Unscheduled Visits 
If any subject needs to return to the site prior to her next scheduled visit, site staff should follow 
the Unscheduled Visit procedures outlined in section 5. Site staff may conduct additional study 
procedures if required. 
12.8. 
Prior and Concomitant Medications and Procedures 
All prior medications taken within 90 days before randomization will be recorded. All 
medications (including over-the-counter medications) taken by the subject on Day 1 through the 
end of the study must be recorded. Any prior treatments (medications or procedures) for EFP 
through the end of the study must be recorded on the appropriate eCRF page. 
Additionally, any diagnostic, therapeutic or surgical procedures performed during the study 
period should be recorded including the date, indication for and description of the procedure. 
12.8.1. 
Prohibited Medications or Procedures 
The following medications are prohibited for randomized subjects during the study: 
anticoagulants (warfarin, heparin, direct thrombin inhibitors, Factor X inhibitors) and antiplatelet 
agents (aspirin >150 mg/day and P2Y12 inhibitors, such as clopidogrel), which can cause 
additional bruising. However the use of aspirin at a dose level of ≤150 mg per day will be 
permitted during study. 
Procedures listed in exclusion criterion #4 (section 11.2, Exclusion Criterion #4) are prohibited 
for randomized subjects during the study. 
Table 4: 
Concomitant Medication Restrictions for Subjects during the Treatment 
Phase of Study 
Drug Class 
Restrictions 
Anticoagulants 
Subjects cannot take antiplatelet agents or anticoagulants (except for 
≤150 mg aspirin daily) within 7 days before and 7 days after the dosing 
administration. 
12.9. 
Treatment Compliance 
Randomized subjects will receive study drug administered by an Investigator at the 
Investigator’s site. 
Accidental or intentional overdoses should be reported to the Sponsor/designee promptly (see 
section 14.6.2.1, Overdose). 
12.10. 
Blinding and Randomization 
On Day 1, if each of the buttocks (ie, both buttocks) again meet the criteria (3 or 4 on the 
PR-PCSS and CR-PCSS), one buttock will be randomly assigned by the IWRS as the target 
buttock for the primary efficacy endpoint. Subjects, investigators, site personnel, and Endo 
personnel will be blinded to the identification of the target buttock.  
On Day 1, if each of the buttocks (ie, both buttocks) again meet the criteria (3 or 4 on the 
PR-PCSS and CR-PCSS), the subject will be randomized to a treatment group. The interactive 

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web response system (IWRS) will randomly assign each subject to a treatment group (EN3835 
0.84 mg per buttock × two buttocks or placebo) in a 1:1 ratio within an investigational site. The 
treatment group will remain blinded to the Investigator, subjects, all site personnel, and the 
sponsor. The IWRS will assign the subject study drug kit numbers associated with the 
randomized treatment. At Day 22 and 43 visits, the IWRS will again assign the subject study 
drug kit numbers associated with the randomized treatment assigned at Day 1.  
All precautions will be taken to ensure that the blinding of EN3835 and placebo is maintained 
throughout the study period. Unblinding will not be permitted by the study site unless it is 
deemed necessary for treatment of a medical emergency. Before breaking the blind, the 
Investigator should make every attempt to contact the Medical Monitor to discuss the necessity 
of breaking the blind. The study site will have the ability to immediately determine treatment 
identification in the event of an emergency by using the unblinding function within the IWRS, 
however, the Medical Monitor must be notified immediately. The Investigator will be required to 
make a full written explanation of the reason for unblinding the subject and the date. In the event 
that a subject is unblinded prior to contacting the Medical Monitor, the Investigator must provide 
this information in writing to the Medical Monitor as soon as possible. Breaking the blind at the 
investigative site will immediately disqualify the subject from further participation in the study. 
In addition, the event(s) leading to emergency unblinding must be reported as an SAE according 
to instructions in section 14.5.2, Reporting Serious Adverse Events. 
In addition, it may be necessary for the Investigator or qualified designee to unblind a subject as 
a result of a clinically significant finding noted during safety review by the Investigator, Safety 
Monitor, Medical Monitor and/or qualified designee that might jeopardize subject safety. 
 

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13. 
ASSESSMENT OF EFFICACY 
13.1. 
Efficacy Measurements 
13.1.1. 
Digital Photography  
Although digital photographs are not direct efficacy measurements, digital photography will be 
utilized in the assessment of certain efficacy measurements ie to assess certain cellulite severity 
parameters at specific intervals (see section 5, Schedule of Events). At the Screening visit, the 
Investigator or qualified designee will photograph each buttock using a Sponsor-supplied 
standardized digital camera in a standardized manner. The subject will be standing for each 
photography session and will be wearing a standardized photographic garment as described in 
the Photography Manual. The Investigator or qualified designee will photograph each of the two 
buttocks while the subject is standing in a consistent, standardized relaxed standing pose, 
ie, standing position with relaxed gluteus muscles, at the following time points: 
• Screening (no markings of dimples or injection site) - each of the two buttocks 
• Before and after marking dimples and injection sites (prior to injections) on Days 1, 
22, and 43 - each of the two buttocks 
• During the Day 71 visit (end of study/early termination) (no dimple or injection site 
markings) - each of the two buttocks 
All photographs from this study are the property of Endo and may be utilized for clinical 
development, scientific communication, marketing, regulatory purposes, and/or legal 
applications as required/desired by Endo. 
13.1.2. 
Subject and Investigator Cellulite Assessments 
Investigator cellulite assessments are independent of the subject assessments. Therefore, all 
subject cellulite assessments must be completed before the Investigator’s cellulite assessments 
are initiated. The subject assessments will be done using a subject-assigned password protected 
electronic patient reported outcome (ePRO) system and the Investigator and study site personnel 
will not have access to the subject’s assessments or password; the clinician assessment will be 
recorded in an investigator-assigned password protected system and the subject will not have 
access to the Investigator’s assessments or password. Subject assessments will be done alone 
with no study site personnel in the room. Investigators will be instructed not to verbalize their 
ratings while in the presence of the subject. 
13.1.2.1. Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) 
The PR-PCSS will be conducted for the purpose of assessing the severity of cellulite in the 
buttock. The scale is a 5-level photonumeric scale developed specifically for patients and used 
by the subject to assess the severity of their cellulite in the buttocks by viewing digital images of 
each of their buttocks captured by photography at the visit; the ratings range from 0 (None) to 
4 (Severe) with labels and descriptors to aid the subject in the assessments.  

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At Screening and at the beginning of their visits on Day 1, Day 22, Day 43, and Day 71, subjects 
will have digital photographs taken of each of their two buttocks. Subjects will be given 
instructions in the proper use (Patient Instructions for Use of PR-PCSS) of the PR-PCSS and 
then perform the PR-PCSS for each of the buttocks (Appendix B). While viewing the digital 
images of each of their buttocks on a standardized computer monitor and using PR-PCSS for 
buttock, subjects will be instructed to answer the following question for each buttock: Today, 
how would you rate the severity of your cellulite in the area displayed using the PR-PCSS? The 
subject will be given the following explanations: Please try to match the severity of your 
cellulite, as seen in this digital image, with one of the cellulite levels on the PR-PCSS. Please 
look at the image of your cellulite and the pictures, labels, and descriptions on the PR-PCSS 
carefully before selecting your answer. If you feel that your cellulite level is between 2 of the 
levels, please select the level that is closest to your image. If you feel that your cellulite is exactly 
halfway between two PR-PCSS levels of cellulite severity, please select the more severe 
response. 
The subject will enter their rating electronically into an ePRO system; the Investigator and other 
site personnel will be blinded to the rating entered by the subject. This variable will be entered 
directly into the EDC system, thus the electronic database will serve as the direct point of data 
capture and will serve as source for this variable. 
13.1.2.2. Subject Global Aesthetic Improvement Scale (S-GAIS) 
Subjects will complete the S-GAIS for each of the buttocks as described below at the Day 22, 
Day 43, and Day 71 study visits using the pre-treatment Day 1 digital image (Baseline) of each 
of the buttocks for comparison. 
All treated subjects will be instructed to answer the following question for each buttock:  
How would you rate the appearance of your treated cellulite after treatment? 
The S-GAIS assessment will occur after the subject has completed the PR-PCSS assessment to 
avoid introducing potential bias to the static PR-PCSS assessment. The subject will view each of 
their pre-treatment Day 1 digital images alongside their Day 22, Day 43 or Day 71/End of study 
visit digital images of each of their buttocks to aid in the assessment (Table 5). Subjects will 
provide a rating from those below that best represents their answer for each treated buttock. 
This variable will be entered directly into the EDC system, thus the electronic database will serve 
as the direct point of data capture and will serve as source for this variable. 

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Table 5: 
Subject Global Aesthetic Improvement Scale (S-GAIS) 
Rating 
Response Option 
Description 
+3 
Very much improved 
My treated cellulite looks very much better. 
+2 
Much improved 
My treated cellulite looks much better, but additional treatment 
would slightly improve the result. 
+1 
Improved 
My treated cellulite looks better, but additional treatment is 
necessary. 
0 
No change 
My treated cellulite looks essentially the same as it did 
originally. 
−1 
Worse 
My treated cellulite looks worse than it did originally. 
−2 
Much worse 
My treated cellulite looks much worse than it did originally. 
−3 
Very much worse 
My treated cellulite looks very much worse than it did 
originally. 
13.1.2.3. Patient Reported Cellulite Impact Scale (PR-CIS) 
At the Day 1 visit and the Day 71 visit, subjects will be instructed to answer 6 questions related 
to the areas selected for treatment on their buttocks on the PR-CIS (Appendix D) while viewing 
digital images of their buttocks. The PR-CIS assesses the visual and emotional impact of cellulite 
(happy, bothered, self-conscience, embarrassed, looking older, or looking overweight or out of 
shape) using a 6-question survey, with each question rated on a numerical rating scale from 
0 (not at all) to 10 (extremely). 
This variable will be entered directly into the EDC system, thus the electronic database will serve 
as the direct point of data capture and will serve as source for this variable. 
13.1.2.4. Subject Satisfaction with Cellulite Treatment Assessment 
At the Day 71 visit, subjects will be instructed to answer a question related to their treated 
buttocks. Subjects will be given a list of responses and they will provide a rating from those 
below that best represents their answer (Table 6). 
Today, how satisfied are you with the results of the cellulite treatment you received on the 
specific area or areas on your buttocks that were treated? 
This variable will be entered directly into the EDC system, thus the electronic database will serve 
as the direct point of data capture and will serve as source for this variable. 
Table 6: 
Subject Satisfaction with Cellulite Treatment Assessment - Buttocks 
Rating 
Description 
+2 
I am very satisfied with the cellulite treatment on my buttocks. 
+1 
I am satisfied with the cellulite treatment on my buttocks. 
0 
I am neither dissatisfied nor satisfied with the cellulite treatment on my buttocks. 
-1 
I am dissatisfied with the cellulite treatment on my buttocks. 
-2 
I am very dissatisfied with the cellulite treatment on my buttocks. 

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13.1.2.5. Subject Self-Rating Scale (SSRS) 
The SSRS is a measure that assesses subject satisfaction with appearance in association with 
cellulite on the buttocks using whole numbers on a 7-level scale that ranges from 0 (extremely 
dissatisfied to 6 (extremely satisfied). The patient will be asked to respond to the question related 
to the satisfaction with appearance of the cellulite on their buttocks on the appropriate visit day 
(note Day 71 question is different than Day 1 question). No photographs or reference to previous 
ratings or evaluations will be used. Subjects will be given a list of responses and they will 
provide a rating from those below that best represents their answer (Table 7); the list of 
responses is the same for Day 1 and for Day 71. 
On Day 1 (Baseline), subjects will be instructed to answer: Considering your appearance in 
association with your cellulite on your buttocks, how satisfied do you feel with your appearance 
at the present time? 
On Day 71, subjects will be instructed to answer: Considering your appearance in association 
with your cellulite on your buttocks, how satisfied do you feel with your appearance at the 
present time whether or not in your judgment it is due entirely to treatment with EN3835? 
This variable will be entered directly into the EDC system, thus the electronic database will serve 
as the direct point of data capture and will serve as source for this variable. 
Table 7: 
Subject Self-Rating Scale (SSRS) 
Rating 
Response Option 
6 
Extremely satisfied 
5 
Satisfied 
4 
Slightly satisfied 
3 
Neither satisfied nor dissatisfied 
2 
Slightly dissatisfied 
1 
Dissatisfied 
0 
Extremely dissatisfied 
13.1.2.6. Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 
The CR-PCSS will be conducted for the purpose of assessing the severity of cellulite in the 
buttock. The scale is a 5-level photonumeric scale developed specifically for clinicians and used 
by the Investigator to assess the severity of the subject’s cellulite in each buttock by live 
assessments; the ratings range from 0 (None) to 4 (Severe) with labels and descriptors to aid the 
Investigator in the assessments. 
Investigators will be trained and qualified on the use of the CR-PCSS prior to assessing any 
subjects. 
At the Screening visit, the Investigator will determine severity of cellulite of each of the 
two buttocks via live assessment of the subject using the CR-PCSS for buttock (Appendix C) 
after the subject has completed her self-assessment using the PR-PCSS. Before injections on 
treatment visits Day 1, Day 22, and Day 43, and on visit Day 71; Investigators will evaluate each 
of the two buttocks by live assessments using the CR-PCSS for the buttock to make his/her 

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evaluation. At each visit, the Investigator will make his/her assessment independently and after 
the subject has conducted her self-assessment using the PR-PCSS. 
This variable will be entered directly into the EDC system, thus the electronic database will serve 
as the direct point of data capture and will serve as source for this variable. 
13.1.2.7. Investigator Global Aesthetic Improvement Scale (I-GAIS) 
On the Day 22, Day 43, and Day 71 study visits, the Investigator will determine the degree of 
improvement of each buttock by comparing the cellulite from the Day 1 pre-treatment (Baseline) 
digital image of each buttock to the cellulite seen in a live assessment (Table 8). The I-GAIS 
assessment will occur after the CR-PCSS assessment (section 13.1.2.6) to avoid introducing 
potential bias to the static CR-PCSS assessment by the Investigator. For each buttock, the 
Investigator will provide the rating from those below that best represents his/her answer. 
This variable will be entered directly into the EDC system, thus the electronic database will serve 
as the direct point of data capture and will serve as source for this variable. 
Table 8: 
Investigator Global Aesthetic Improvement Scale (I-GAIS) 
Rating 
Response Option 
Description 
+3 
Very much improved 
Optimal cosmetic result from treatment of the treated dimples 
+2 
Much improved 
Marked improvement in the treated area appearance from 
before treatment, but not completely optimal 
+1 
Improved 
Obvious improvement in the treated area appearance from 
before treatment, but additional treatment is indicated 
0 
No change 
The treated area appearance is essentially the same as before 
treatment 
−1 
Worse 
The treated area appearance is worse than before treatment 
−2 
Much worse 
Marked worsening in appearance from the initial condition 
−3 
Very much worse 
Obvious worsening in appearance from the initial condition 

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14. 
ASSESSMENT OF SAFETY 
14.1. 
Definitions 
14.1.1. 
Adverse Events 
An adverse event (AE) is any unfavorable or unintended change in body structure (signs), body 
function (symptoms), laboratory result (eg, chemistry, ECG, X-ray, etc), or worsening of a 
pre-existing condition associated temporally with the use of the study medication whether or not 
considered related to the study medication. Adverse events will be captured once a subject has 
signed the informed consent. AEs include: 
• Changes in the general condition of the subject 
• Subjective symptoms offered by or elicited from the subject 
• Objective signs observed by the Investigator or other study personnel 
• All concurrent diseases that occur after the start of the study, including any change in 
severity or frequency of pre-existing disease 
• All clinically relevant laboratory abnormalities or physical findings that occur during 
the study 
A treatment-emergent adverse event (TEAE) is any condition that was not present prior to 
treatment with study medication but appeared following treatment, was present at treatment 
initiation but worsened during treatment, or was present at treatment initiation but resolved and 
then reappeared while the individual was on treatment (regardless of the intensity of the AE 
when the treatment was initiated). 
All AEs, including both observed or volunteered problems, complaints, signs or symptoms must 
be recorded on the AE page of the eCRF, regardless of whether associated with the use of study 
medication. This would include AEs resulting from concurrent illness, reactions to concurrent 
medication use, or progression of disease states (excluding the disease under study). A condition 
present at baseline that worsens after initiation of study treatment will be captured as an AE; the 
onset date will be the date the event worsened. The AE should be recorded in standard medical 
terminology when possible. 
14.1.2. 
Serious Adverse Events 
A serious adverse event (SAE) is defined as an AE that: 
• Results in death 
• Is immediately life-threatening (there is an immediate risk of death from the AE as it 
occurred; this does not include an AE that had it occurred in a more serious form may 
have caused death) 
• Results in or prolongs an inpatient hospitalization (Note: a hospitalization for elective 
or pre-planned surgery, procedure, or drug therapy does not constitute an SAE) 

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• Results in permanent or substantial disability (permanent or substantial disruption of 
one’s ability to conduct normal life functions) 
• Is a congenital anomaly/birth defect (in offspring of a subject using the study 
medication regardless of time to diagnosis) 
• Is considered an important medical event 
Important medical events are defined as events that, based upon appropriate medical judgment, 
may jeopardize the subject and may require medical or surgical intervention to prevent one of the 
other serious outcomes. Examples of important medical events include malignancy, allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias 
or convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
14.2. 
Monitoring Adverse Events 
At each visit, subjects will be queried regarding any AEs that have occurred since the last visit. 
Subjects will be asked to volunteer information concerning AEs with a non-leading question 
such as, “How do you feel?” Study site personnel will then record all pertinent information in the 
source documents and the eCRF. The study drug compliance record should also be reviewed to 
detect potential overdoses (intentional/unintentional). 
14.3. 
Relationship to Study Drug 
The degree of “relatedness” of the AE to the study medication must be described using the 
following scale: 
• Not related indicates that the AE is definitely not related to the study medication. 
• Unlikely related indicates that there are other, more likely causes and study 
medication is not suspected as a cause. 
• Possibly related indicates that a direct cause and effect relationship between study 
medication and the AE has not been demonstrated, but there is evidence to suggest 
there is a reasonable possibility that the event was caused by the study medication. 
• Probably related indicates that there is evidence suggesting a direct cause and effect 
relationship between the AE and the study medication. 
It is the Sponsor’s policy to consider “Probably related” and “Possibly related” causality 
assessments as positive causality. “Not related” and “Unlikely related” causality assessments are 
considered as negative causality. 
Assessments will be recorded on the eCRF and must indicate clearly the relationship being 
assessed. For example, an AE that appears during a placebo run-in phase would be assessed with 
respect to the placebo treatment received and/or study procedures conducted during this phase. If 
the AE continued into an active treatment phase, the relationship would be assessed for the active 
treatment phase only if the AE worsened. 

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14.4. 
Intensity Assessment 
The intensity (or severity) of AEs is characterized as mild, moderate, or severe: 
• Mild AEs are usually transient, requiring no special treatment, and do not interfere 
with the subject’s daily activities. 
• Moderate AEs introduce a low level of inconvenience or concern to the subject and 
may interfere with daily activities, but are usually ameliorated by simple therapeutic 
measures. 
• Severe AEs interrupt a subject’s usual daily activity and typically require systemic 
drug therapy or other treatment. 
When the intensity category of an AE changes, the greatest intensity during that continuous 
episode should be recorded. 
14.5. 
Reporting Adverse Events and Serious Adverse Events 
14.5.1. 
Reporting Adverse Events 
Throughout the study, AEs will be documented on the source document and on the appropriate 
page of the eCRF whether or not considered treatment-related. This includes any new signs, 
symptoms, injury or illness, including increased severity of previously existing signs, symptoms, 
injury, or illness. Conditions existing prior to screening will be recorded as part of the subject’s 
medical history. The Investigator is responsible for assessing the relationship of AEs to the study 
medication; relationship will be classified as not related, unlikely related, possibly related, or 
probably related. 
All AEs will be collected by the Investigator from the time of signing the informed consent 
through 28 days after the last dose of study medication; this includes any AEs that are ongoing at 
the time of completion/termination of the study. All ongoing AEs must be followed until 
resolution or for 30 days after the subject’s last study visit, whichever comes first. 
14.5.2. 
Reporting Serious Adverse Events 
Any SAE, including death resulting from any cause, which occurs to any subject participating in 
this study must be reported via email or fax by the Investigator using the Endo Clinical Trial 
Report Form for SAEs within 24 hours of first becoming aware of the SAE. SAEs will be 
collected by the Investigator from the time of signing the informed consent through 28 days after 
the last dose of study medication. SAEs that occur within 28 days, following cessation of the 
study treatment, or within 30 days, following premature discontinuation from the study for any 
reason, must also be reported within the same timeframe. Any SAE that is felt by the Investigator 
to be related to the study medication must be reported regardless of the amount of time since the 
last dose received. Follow-up information collected for any initial report of an SAE must also be 
reported to the Sponsor within 24 hours of receipt by the Investigator. 
All SAEs will be followed until resolution, stabilization of condition, or until follow-up is no 
longer possible. 

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In the event discussion is necessary regarding treatment of a subject, call the Medical 
Monitor (see contact information in section 3). 
All SAEs should be sent via the email address, or faxed to the fax number, provided in 
section 3. 
The Sponsor will determine whether the SAE must be reported within 7 or 15 days to regulatory 
authorities in compliance with local and regional law. If so, the Sponsor (or the Sponsor’s 
representative) will report the event to the appropriate regulatory authorities. The Investigator 
will report SAEs to the IRB per their IRB policy. 
14.5.2.1. Follow-up Procedures for Serious Adverse Events 
To fully understand the nature of any SAE, obtaining follow-up information is important. 
Whenever possible, relevant medical records such as discharge summaries, medical 
consultations, and the like should be obtained. In the event of death, regardless of cause, all 
attempts should be made to obtain the death certificate and any autopsy report. These records 
should be reviewed in detail, and the Investigator should comment on any event, lab 
abnormality, or any other finding, noting whether it should be considered a serious or 
non-serious AE, or whether it should be considered as part of the subject’s history. In addition, 
all events or other findings determined to be SAEs should be identified on the follow-up SAE 
form and the Investigator should consider whether the event is related or not related to study 
drug. 
14.6. 
Special Reporting Situations 
14.6.1. 
Adverse Events of Special Interest 
Adverse events such as bruising, ecchymosis, hematomas, and contusions that occur remote to 
the site of drug administration, or any hypersensitivity reactions, including anaphylaxis, will be 
recorded and evaluated for seriousness and severity (see section 14.1.1, Adverse Events or 
section 14.1.2, Serious Adverse Events). 
In addition, local AEs associated with the injection site, including bruising, pain, nodules/mass, 
ulceration, erythema, pruritus, swelling, and/or induration, will be recorded and evaluated for 
seriousness and severity (see as appropriate, section 14.1.1, Adverse Events or section 14.1.2, 
Serious Adverse Events) 
14.6.2. 
Overdose/Misuse/Abuse 
14.6.2.1. Overdose 
Study drug overdose is any accidental or intentional use of study drug in an amount higher than 
the dose indicated by the protocol for that subject. Study drug compliance (see section 12.9) 
should be reviewed to detect potential instances of overdose (intentional or accidental). 
Any study drug overdose during the study should be noted on the study medication eCRF. 
An overdose is not an AE per se, however all AEs associated with an overdose should both be 
entered on the Adverse Event eCRF and reported using the procedures detailed in section 14.5.2, 
Reporting of Serious Adverse Events, even if the events do not meet seriousness criteria. If the 

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AE associated with an overdose does not meet seriousness criteria, it must still be reported using 
the Endo Clinical Trial Report Form for SAEs and in an expedited manner, but should be noted 
as non-serious on the form and the Adverse Event eCRF. 
14.6.3. 
Pregnancy 
Subjects should be instructed to immediately notify the Investigator of any pregnancies. 
Any pregnancy that occurs in a subject during this clinical study will be reported for tracking 
purposes only. All subject pregnancies that are identified during or after this study, where the 
estimated date of conception is determined to have occurred during study drug therapy or within 
28 days of the last dose of study medication need to be reported, followed to conclusion, and the 
outcome reported, even if the subject is discontinued from the study. The Investigator should 
report all pregnancies within 24 hours using the Initial Pregnancy Report Form, and any 
pregnancy-associated SAE using the SAE report form, according to the usual timelines and 
directions for SAE reporting provided in section 14.5.2. Monitoring of the pregnancy should 
continue until conclusion of the pregnancy; 1 or more Follow-up Pregnancy Report Form(s) 
detailing progress, and a Two Month Follow-up Pregnancy Report Form detailing the outcome, 
should be submitted. 
Pregnancy itself is not regarded as an AE unless there is suspicion that the investigational 
product under study may have interfered with the effectiveness of a contraceptive medication. 
Likewise, elective abortions without complications are not considered AEs. Any SAEs 
associated with pregnancy (eg, congenital abnormalities/birth defects/spontaneous miscarriages 
or any other serious events) must additionally be reported as such using the SAE report form. 
Spontaneous miscarriages should also be reported and handled as SAEs. 
A subject who becomes pregnant must be withdrawn from the study. Attempts to obtain the 
pregnancy follow-up and pregnancy outcome information detailed above are necessary even if a 
subject discontinues treatment because of pregnancy. 
14.6.4. 
AEs/SAEs Experienced by Non-subjects Exposed to Study Medication 
Non-subjects are persons who are not enrolled in the study but have been exposed to study 
medication, including instances of diversion of study medication. All such AEs/SAEs occurring 
in non-subjects from such exposure will be reported to the Endo PVRM Department (when the 
non-subject agrees) on the departmental form for serious adverse experiences regardless of 
whether the event is serious or not. Instructions for completing the form for events experienced 
by non-subjects will be provided. SAEs occurring in non-subjects exposed to study medication 
will be processed within the same SAE reporting timelines as described in section 14.5.2, 
Reporting Serious Adverse Events. Additionally, the drug accountability source documentation 
at the site should reflect this occurrence. 
14.7. 
Clinical Laboratory Determinations 
Clinical laboratory tests will be conducted according to the Schedule of Events (section 5). 
Clinical laboratory tests will be performed by a designated central laboratory. Each site will be 
provided with instructions on specimen collection, preparation, packaging and transport. Refer to 
the central laboratory manual for further information regarding sample collection, handling, and 
labeling. The results of the tests will be returned to the investigational sites.  

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Clinical laboratory test data will be reviewed by the Investigator, or designee, and additional 
clinical laboratory tests may be ordered at his/her discretion (eg, if the results of any clinical 
laboratory test falls outside the reference range or clinical symptoms necessitate additional 
testing to ensure safety). Any additional testing will be performed by the designated central 
laboratory. The Investigator or qualified designee must acknowledge the review of laboratory 
results. 
The Investigator will review all abnormal lab results for potentially clinically important. Any 
abnormal clinical laboratory test result meeting the Investigator’s criteria for potentially 
clinically important (refer to central laboratory manual) will be recorded as an AE or SAE as 
appropriate (see section 14.1.1, Adverse Events, and section 14.1.2, Serious Adverse Events). 
Laboratory results will be sent electronically to Endo Pharmaceuticals Inc. for data management. 
Clinical laboratory parameters that will be measured in this study are listed in Table 9. 
Table 9: 
Clinical Laboratory Tests 
Hematology 
Biochemistry 
Urinalysis 
Hemoglobin 
Hematocrit 
Red blood cell 
White blood cell (WBC) 
Platelets 
WBC Differential 
Glucose 
Sodium 
Potassium 
Calcium 
Chloride 
CO2 
Inorganic phosphate 
Blood urea nitrogen  
Creatinine 
Creatinine clearance (estimated)  
Aspartate transaminase (AST) 
Alanine transaminase (ALT) 
Gamma-glutamyl transferase (GGT) 
Total bilirubin (TBL) (direct bilirubin reflex if elevated) 
Albumin 
Alkaline phosphatase (ALP) 
Uric acid 
Glucose 
Protein 
Specific gravity 
pH 
Ketones 
Bilirubin 
Urobilinogen 
Nitrite 
Blood* 
Leukocytes* 
* Microscopic examination will be performed if blood or leukocytes are detected by dipstick. 
For women of childbearing potential, a serum pregnancy test will be performed at Screening and 
Day 71/End of Study/Early Termination, and urine pregnancy tests will be performed at Day 1, 
Day 22, and Day 43 (refer to section 5). Female subjects of childbearing potential must have a 
negative pregnancy test at the Screening Visit and at Day 1 (Baseline), Day 22, and Day 43 to be 
randomized and/or receive treatment in the study. If necessary, additional urine pregnancy tests 
can be performed at any time during the study at the discretion of the Investigator. Urine 
pregnancy test kits will be supplied by the Sponsor. 

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14.11. 
Physical Examination 
A complete physical examination will be performed at the Screening Visit. All examinations will 
be performed by a physician or health professional listed on the Form FDA 1572 and licensed to 
perform physical examinations. Height and body weight will be measured and recorded at 
screening. 
The Investigator will review all physical exam findings for clinical significance. Any physical 
exam finding meeting the Investigator’s or Sponsor’s criteria for clinical significance will be 
recorded as an AE or SAE as appropriate (see section 14.1.1, Adverse Events and section 14.1.2, 
Serious Adverse Events). 
At screening, the Investigator will also assess the subject’s skin type using the Fitzpatrick scale 
(Table 11). Only the Fitzpatrick Scale shown below may be used during the study. 
Table 11: 
Fitzpatrick Scale 
I 
Pale white skin, blue/hazel eyes, blond/red hair 
Always burns, does not tan 
II 
Fair skin, blue eyes 
Burns easily, tans poorly 
III 
Darker white skin 
Tans after initial burn 
IV 
Light brown skin 
Burns minimally, tans easily 
V 
Brown skin 
Rarely burns, tans darkly easily 
VI 
Dark brown or black skin 
Never burns, always tans darkly 
Follow-up body weight will be measured before injection on Day 22 and Day 43 and at the 
Day 71 visit. 
14.12. 
Other Safety Assessments 
Not applicable. 

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15. 
ASSESSMENT OF PHARMACOKINETICS 
Not applicable. 

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16. 
ASSESSMENT OF PHARMACODYNAMICS 
Not applicable. 

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17.2. 
Subject Populations 
Four (4) populations are considered in the statistical analysis of the study: safety, intent-to-treat 
(ITT), modified ITT (mITT), and per-protocol (PP). 
17.2.1. 
Safety Population 
The safety population is defined as all enrolled subjects who have received at least one injection 
of study medication. All safety parameters will be summarized based on this population. 
17.2.2. 
Intent-to-Treat (ITT) Population 
The ITT population is defined as all randomized subjects who have received at least one 
injection of study medication. All demographic and baseline characteristic summaries will be 
based on this population. The primary and key secondary efficacy parameters will be 
summarized based on this population. 
17.2.3. 
Modified Intent-to-Treat (mITT) Population 
The mITT population is defined as all intent-to-treat subjects with a baseline and at least 1 
post-injection evaluation of both the Investigator CR-PCSS and subject PR-PCSS for both the 
target and non-target buttocks. All secondary and supportive efficacy evaluations will be based 
on the mITT population. 
17.2.4. 
Per-Protocol (PP) Population 
The per-protocol population is defined as the mITT subjects without any of the following :  
• Placebo-assigned subject receives EN3835 treatment 
• EN3835-assigned subject receives placebo treatment only throughout study 
• Any subject receives protocol-prohibited medications 
• Subject lacking PR-PCSS and/or CR-PCSS assessment at Day 71 
• Any major protocol deviation that is deemed as impact subject efficacy 
This population may be used in the efficacy sensitivity analysis. 
17.3. 
Subject Disposition 
The number of subjects included in each study population will be summarized by treatment 
group. Subjects excluded from the safety and efficacy (eg, ITT) populations will be listed by 
treatment group. 
The number and percentage of subjects completed and prematurely discontinued during the 
treatment period will be presented for each treatment group and pooled across treatment groups. 
Screen failures (ie, screened but not randomized subjects) and the associated failure reasons will 
be tabulated overall. Reasons for premature discontinuation from the treatment period as 
recorded on the termination page of the eCRF will be summarized (number and percentage) by 
treatment group for all randomized subjects. Percentage of premature discontinuations will be 
compared between treatment groups. 

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17.4. 
Demographics and Other Baseline Characteristics 
The summarization of demographic variables (eg, age, sex, race, weight, height, and body mass 
index [BMI]), medical and surgical history, and other baseline characteristics relevant to the 
indication studied in the study will be described. 
Demographic characteristics, including sex, age, age group, race, height, and weight, will be 
summarized by treatment group, for the ITT population, using descriptive statistics. All 
screening characteristics and medical information will also be summarized by treatment group 
using descriptive statistics. The descriptive summaries will include frequency tables for all 
categorical response variables and n, mean, standard deviation (SD), median, minimum, and 
maximum for all continuous variables. 
17.5. 
Efficacy Analyses 
All efficacy endpoints including supportive efficacy analysis will be summarized as percentages. 
The dichotomous secondary endpoints (ie, responder endpoints) will be analyzed using a 
Cochran-Mantel-Haenszel test adjusted for Investigator. Changes in the PR-PCSS ratings and 
CR-PCSS ratings from baselines, S-GAIS scores, I-GAIS scores, and SSRS scores will be 
analyzed using the Wilcoxon rank sum test. Changes in PR-CIS from baselines will be analyzed 
using an analysis of covariance (ANCOVA) adjusted for baseline values. All the tests are two-
sided. 
The primary endpoint will be summarized as percentages and analyzed using a Cochran-Mantel-
Haenszel test that compares the 2 treatment groups and adjusts for Investigator at a level of 
significance of 0.05 based on the ITT population. Any subject who does not have an evaluation 
of CR-PCSS and/or PR-PCSS at Day 71 will be classified as a non-responder. 
The key secondary efficacy analyses will be analyzed in the same manner as the primary 
endpoint based on the ITT population. Any subject who does not have an evaluation at Day 71 
will be classified as a non-responder for the analyses. The family #1 key secondary efficacy 
analyses will be performed only if the primary efficacy analysis is significant (p ≤ 0.05; 
gatekeeping strategy). Similarly family #2 key secondary efficacy analyses will be performed 
only if at least one of the key secondary efficacy endpoints of family #1 is significant (p ≤ 
0.0125; parallel gatekeeping strategy) and family #3 key secondary efficacy analyses will be 
performed only if at least one of the key secondary efficacy endpoints of family #2 is significant 
(parallel gatekeeping strategy). Within a family of key secondary efficacy endpoints, the 
Bonferroni method will be performed to relocate unused alpha for testing each endpoint to assure 
an overall error rate of p ≤ 0.05. The details of the testing procedures will be provided in the 
statistical analysis plan for the study. 
All supportive endpoints will be summarized as subject counts and percentages for categorical 
data or n, mean, SD, median, minimum, and maximum for continuous data. All the supportive 
analyses will be performed based on all observed data (ie, missing data not imputed) in the mITT 
population at all visits without multiplicity adjustment. This analysis will also be performed at 
Day 71 with missing data at Day 71 imputed by a last observation carried forward (LOCF) 
approach if subjects have at least one post-dose assessment. The dichotomous secondary 
endpoints (ie, responder endpoints) will be analyzed using a Cochran-Mantel-Haenszel test 
adjusted for Investigator. Changes in the PR-PCSS ratings and CR-PCSS ratings from baselines, 

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S-GAIS scores, I-GAIS scores, and SSRS scores will be analyzed using the Wilcoxon rank sum 
test. Changes in PR-CIS from baselines will be analyzed using an analysis of covariance 
(ANCOVA) adjusted for baseline values. 
17.5.1. 
Primary Efficacy Variable 
The primary efficacy variable is the proportion of 2-level composite responders at Day 71 
defined as subjects with: 
• an improvement in severity from baseline (Day 1 visit) of at least 2 levels of severity 
in the CR-PCSS as assessed live by the Investigator of the target buttock, and  
• an improvement in severity from baseline of at least 2 levels of severity in the 
PR-PCSS by the subject while viewing the digital image of the target buttock. 
A subject will be considered a responder if these criteria are met in the randomized target buttock 
of that subject.  
Sensitivity analyses for the primary endpoint will include: 
• ITT subjects with missing data handled by multiple imputation (MI) approach 
• ITT subjects with missing data handled by an LOCF approach 
• mITT subjects with missing data handled by an LOCF approach 
• Observed data only (no missing data handling) 
• Per-protocol (PP) subjects with missing data handled by an LOCF approach if 10% or 
more subjects are excluded in the PP population from mITT population 
17.5.2. 
Secondary Efficacy Variables 
17.5.2.1. Key Secondary Variables 
There will be 8 key secondary endpoints grouped in three families of 2 to 4 endpoints per family 
analyzed in hierarchical order. 
• Family #1 – four endpoints: 
− Proportion of 1-level PR-PCSS responders defined as subjects with ≥1-level 
improvement in PR-PCSS severity rating of the target buttock at Day 71 
compared to Day 1 
− Proportion of 2-level PR-PCSS responders defined as subjects with ≥2-level 
improvement in PR-PCSS severity rating of the target buttock at Day 71 
compared to Day 1 
− Proportion of 1-level composite responders of the target buttock (defined as 
subjects with an improvement in severity from baseline of at least 1 level of 
severity in the CR-PCSS of the target buttock assessed live by the Investigator 
and an improvement of severity from baseline of at least 1 level of severity in the 
PR-PCSS of the target buttock) at Day 71 compared to Day 1 

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− Proportion of 2-level composite responders of the non-target buttock at Day 71 
compared to Day 1 
• Family #2 – two endpoints: 
− Proportion of 1-level SSRS responders defined as subjects who were at least 
slightly satisfied at Day 71 (SSRS rating ≥ 4) 
− Change from baseline (Day 1) of the PR-CIS total score at Day 71 
• Family #3 – two endpoints: 
− Proportion of 1-level S-GAIS responders defined as subjects with ≥1-level 
improvement (improved, much improved or very much improved) in the S-GAIS 
assessment of the target buttock at Day 71 
− Proportion of 2-level S-GAIS responders defined as subjects with ≥2-level 
improvement (much improved or very much improved) in the S-GAIS assessment 
of the target buttock at Day 71 
Sensitivity analyses for the key secondary endpoints will include: 
• ITT subjects with missing data handled by MI approach 
• ITT subjects with missing data handled by an LOCF approach 
• mITT subjects with missing data handled by an LOCF approach 
• Observed data only (no missing data handling) 
• Per-protocol (PP) subjects with missing data handled by an LOCF approach if 10% or 
more subjects are excluded in the PP population from mITT population 
17.5.3. 
Supportive Efficacy Variables 
17.5.3.1. Supportive Variables 
The supportive variables will evaluate assessments at various study time points and using various 
populations. 
• Proportion of 2-level PR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 2 levels of severity in the PR-PCSS of the target 
buttock (Days 22, 43, and 71) 
• Proportion of 2-level PR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 2 levels of severity in the PR-PCSS of the 
non-target buttock (Days 22, 43, and 71) 
• Proportion of 1-level PR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 1 level of severity in the PR-PCSS of the target 
buttock (Days 22, 43, and 71) 
• Proportion of 1-level PR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 1 level of severity in the PR-PCSS of the 
non-target buttock (Days 22, 43, and 71) 

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• Proportion of 2-level PR-PCSS responders of at least one buttock (Days 22, 43, and 
71). A subject will be considered a responder if this criterion is met in the target 
buttock or non-target buttock or both buttocks in that subject. 
• Proportion of 1-level PR-PCSS responders of at least one buttock (Days 22, 43, and 
71). A subject will be considered a responder if this criterion is met in the target 
buttock or non-target buttock or both buttocks in that subject.  
• Proportion of 2-level PR-PCSS responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both the target and non-target buttocks. 
• Proportion of 1-level PR-PCSS responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both the target and non-target buttocks. 
• Proportion of 2-level CR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 2 levels of severity in the CR-PCSS of the target 
buttock (Days 22, 43, and 71) 
• Proportion of 2-level CR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 2 levels of severity in the CR-PCSS of the 
non-target buttock (Days 22, 43, and 71) 
• Proportion of 1-level CR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 1 level of severity in the CR-PCSS of the target 
buttock (Days 22, 43, and 71) 
• Proportion of 1-level CR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 1 level of severity in the CR-PCSS of the 
non-target buttock (Days 22, 43, and 71) 
• Proportion of 2-level CR-PCSS responders of at least one buttock (Days 22, 43, and 
71). A subject will be considered a responder if this criterion is met in the target 
buttock or non-target buttock or both buttocks in that subject. 
• Proportion of 1-level CR-PCSS responders of at least one buttock (Days 22, 43, and 
71). A subject will be considered a responder if this criterion is met in the target 
buttock or non-target buttock or both buttocks in that subject. 
• Proportion of 2-level CR-PCSS responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both the target and non-target buttocks. 
• Proportion of 1-level CR-PCSS responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both the target and non-target buttocks. 
• Proportion of 1-level composite responders of the target buttock (defined as subjects 
with an improvement in severity from baseline of at least 1 level of severity in the 
CR-PCSS of the target buttock assessed live by the Investigator and an improvement 

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of severity from baseline of at least 1 level of severity in the PR-PCSS of that same 
target buttock) (Days 22, 43, and 71) 
• Proportion of 1-level composite responders of the non-target buttock (defined as 
subjects with an improvement in severity from baseline of at least 1 level of severity 
in the CR-PCSS of the non-target buttock assessed live by the Investigator and an 
improvement of severity from baseline of at least 1 level of severity in the PR-PCSS 
of that same non-target buttock) (Days 22, 43, and 71) 
• Proportion of 1-level composite responders of at least one buttock (Days 22, 43, and 
71). A subject will be considered a responder if this criterion is met in the target 
buttock or non-target buttock or both buttocks in that subject. 
• Proportion of 1-level composite responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both the target and non-target buttocks. 
• Proportion of 2-level composite responders of the target buttock (defined as subjects 
with an improvement in severity from baseline of at least 2 levels of severity in the 
CR-PCSS of the target buttock assessed live by the Investigator and an improvement 
of severity from baseline of at least 2 levels of severity in the PR-PCSS of that same 
target buttock) (Days 22, 43, and 71) 
• Proportion of 2-level composite responders of the non-target buttock (defined as 
subjects with an improvement in severity from baseline of at least 2 levels of severity 
in the CR-PCSS of the non-target buttock assessed live by the Investigator and an 
improvement of severity from baseline of at least 2 levels of severity in the PR-PCSS 
of that same non-target buttock) (Days 22, 43, and 71) 
• Proportion of 2-level composite responders of at least one of two buttocks (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in the 
target buttock or non-target buttock or both buttocks in that subject.  
• Proportion of 2-level composite responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both the target and non-target buttocks. 
• Proportion of subjects at each level of the S-GAIS of the target buttock (Days 22, 43, 
and 71) 
• Proportion of subjects at each level of the S-GAIS of the non-target buttock (Days 22, 
43, and 71) 
• Proportion of 1-level S-GAIS responders defined as subjects with a response of at 
least 1 (improved) in the S-GAIS of the target buttock (Days 22, 43, and 71) 
• Proportion of 1-level S-GAIS responders defined as subjects with a response of at 
least 1 (improved) in the S-GAIS of the non-target buttock (Days 22, 43, and 71) 
• Proportion 1-level S-GAIS responders of at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if this criterion is met in the target buttock or 
non-target buttock or both buttocks in that subject. 

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• Proportion of 1-level S-GAIS responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both the target and non-target right buttocks. 
• Proportion of subjects at each level of the I-GAIS of the target buttock (Days 22, 43, 
and 71) 
• Proportion of subjects at each level of the I-GAIS of the non-target buttock (Days 22, 
43, and 71) 
• Proportion of 1-level I-GAIS responders defined as subjects with a response of at 
least 1 (improved) in the I-GAIS of the target buttock (Days 22, 43, and 71). 
• Proportion of 1-level I-GAIS responders defined as subjects with a response of at 
least 1 (improved) in the I-GAIS of the non-target buttock (Days 22, 43, and 71). 
• Proportion of 1-level I-GAIS responders of at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if this criterion is met in the target buttock or 
non-target buttock or both buttocks in that subject.  
• Proportion of 1-level I-GAIS responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both the target and non-target buttocks. 
• Change from baseline (Day 1) of the PR-CIS total score at Day 71 
• Change from baseline (Day 1) of the abbreviated PR-CIS score at Day 71 
• Proportion of subjects with a change from baseline (Day 1) of the PR-CIS ≥ 12 at 
Day 71 
• Proportion of subjects with a change from baseline (Day 1) of the abbreviated 
PR-CIS ≥ 10 at Day 71 
• Proportion of subjects at each level of the SSRS (Day 1 (Baseline) and Day 71) 
• Proportion of 1-level SSRS responders defined as subjects who were at least slightly 
satisfied at Day 71 (SSRS rating ≥ 4) 
• Proportion of subjects at each level of the subject satisfaction with cellulite treatment 
assessment (Day 71) 
• Proportion of satisfied responders (defined as subjects with a response of at least 1 
(ie, 1-Satisfied or 2-Very Satisfied) in the subject satisfaction with cellulite treatment 
assessment (Day 71) 
17.6. 
Safety Analyses 
Safety variables include adverse events, laboratory parameters, vital signs, ECG parameters, and 
physical examinations. For each safety parameter, the last assessment made prior to the first dose 
of study drug will be used as the baseline for all analyses of that safety parameter. 

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17.6.1. 
Prior, Concomitant, and Follow-up Medication 
The World Health Organization (WHO) Drug Dictionary will be used to classify prior and 
concomitant medications by therapeutic class. Prior medication will be defined as any 
medication taken prior to the first dose of study drug. Concomitant medication is defined as any 
medication taken on or after the date of first dose of study drug. 
Prior and concomitant medication use will be summarized descriptively by the number and 
percentage of subjects for each preferred term (generic name from WHO dictionary) by 
treatment. Multiple use of the same medication by a subject will be counted only once. 
17.6.2. 
Study Drug Exposure 
The following information regarding treatment will be summarized per each treated buttock by 
treatment group: 
• Total number of treatment visits 
• Number of subjects who had treatment session done or treatment session not done at 
each treatment visit 
• For subjects who had the treatment session done, the number of subjects who got all 
24 injections at the treatment visit or who received less than 24 injections 
• Number of injections given at each treatment visit  
• Number of dimples treated at each treatment visit  
• Average number of injections per dimple at each treatment visit  
Subjects who did not receive all 3 treatment visits and who did not receive 24 injections at a 
treatment visit will be listed. 
17.6.3. 
Measurement of Treatment Compliance 
Not applicable (the study drug is administered at the site by the study investigator). 
17.6.4. 
Adverse Events 
The Medical Dictionary for Regulatory Activities (MedDRA) will be used to code AEs. 
An AE (classified by preferred term) that started on or after the date of the first dose of the study 
drug will be considered a TEAE if it was not present prior to the first dose of study drug, or was 
present prior to the first dose of study drug but increased in intensity during the treatment period. 
If more than 1 AE is reported prior to the first dose of study drug and coded to the same 
preferred term, then the AE with the greatest intensity will be used as the benchmark for 
comparison to the AEs occurring during the treatment period which were also coded to that 
preferred term. Any AE present prior to the first dose of study drug that increases in intensity 
during the treatment period will be re-entered with a new start date of the date of increased 
intensity. 
Descriptive statistics (the number and percentage) for subjects reporting TEAEs in each 
treatment group will be tabulated by system organ class and preferred term; by system organ 
class, preferred term, and severity; and by system organ class, preferred term, and relationship to 

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study drug. If more than 1 AE is coded to the same preferred term for the same subject, the 
subject will be counted only once for that preferred term using the most severe and most related 
occurrence for the summarization by severity and by relationship to the study drug. 
The by-frequency summaries will also include incidence of the SAEs and non-SAEs by preferred 
term that at least 2% of the subjects in one treatment group. Duration of AEs will be tabulated by 
treatment group. 
The Fisher exact test will be used to compare EN3835 to placebo. 
Listings will be presented for subjects with SAEs, subjects with AEs leading to discontinuation 
of study or study drug, and subjects who die (if any). 
17.6.5. 
Vital Signs 
Descriptive statistics for vital signs (eg, systolic and diastolic blood pressure, pulse rate, and 
body weight) and their changes from baseline at each visit and at the end of study will be 
presented by treatment group. 
Vital sign values are potentially clinically important (PCI) if they meet both the observed value 
criteria and the change from baseline criteria. The criteria for PCI vital sign values will be 
detailed in the Statistical Analysis Plan (SAP). The PCI percentages will be calculated relative to 
the number of subjects with baseline and at least one post-baseline assessment. A supportive 
listing of subject values will be provided including the subject ID, study center, treatment group, 
baseline and post-baseline values. 
The change from baseline for vital signs parameters are compared between EN3835 and placebo 
using an analysis of variance (ANOVA) with a factor of drug (EN3835 or placebo) while the 
Fisher exact test will be used for the incidence of PCI values. 
17.6.6. 
Clinical Laboratory Parameters 
Descriptive statistics for clinical laboratory values in International System of Units (SI units) and 
changes from baseline at Day 71 will be presented by treatment group for each clinical 
laboratory parameter. 
The number and percentage of subjects with potentially clinically important (PCI) post-baseline 
clinical laboratory values will be tabulated by treatment group. The criteria for PCI laboratory 
values will be detailed in the Statistical Analysis Plan (SAP). The PCI percentages will be 
calculated relative to the number of subjects with at least one post-baseline assessment. A 
supportive listing of subjects with post-baseline PCI values will be provided, including the 
subject ID, study center, treatment group, baseline and post-baseline values. 
The change from baseline for clinical laboratory parameters are compared between EN3835 and 
placebo using an ANOVA with a factor of drug (EN3835 or placebo) while the Fisher exact test 
will be used for the incidence of PCI values. 
17.6.7. 
Electrocardiogram 
Not applicable (ECG is done only at screening for the subject’s enrollment eligibility). 

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18.5. 
Study Drug Accountability 
A drug inventory form must be kept current by the site staff designated to be responsible for 
reconstitution and must be made available to the clinical monitor, Endo employees, IRB/IEC, 
and regulatory agencies for routine inspection and accountability during monitoring visits. When 
instructed by Endo, the Investigator agrees to return all original used or unused study drug kits to 
Endo's return vendor. 
18.5.1. 
Study Drug Handling and Disposal 
The Investigator agrees not to supply study drug to any person except to those subjects enrolled 
in the study. The Investigator is responsible for recording the receipt and use of all drugs 
supplied and for ensuring the supervision of the storage and allocation of these supplies. All used 
and unused study drug will be returned, and unit counts will be performed whenever medication 
is returned. The site must account for all study drug received and its use. At the end of the study, 
all used and unused drug supplies will be returned to Endo’s return vendor. 
 

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19. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
19.1. 
Source Documents 
Source documents include but are not limited to original documents, data and records such as 
hospital/medical records (including electronic health records), clinic charts, lab results, subject 
diaries, data recorded in automated instruments, microfilm or magnetic media, and pharmacy 
records, etc. This study allows for direct data entry (DDE) for selected data points as outlined 
below: 
• PR-PCSS 
• CR-PCSS 
• S-GAIS 
• I-GAIS 
• PR-CIS 
• Subject Satisfaction with Cellulite Treatment Assessment 
• SSRS 
All other data points, at a minimum, should have supporting source documentation for entries in 
the eCRF. 
19.2. 
Study Monitoring 
A representative of Endo Pharmaceuticals Inc. will meet with the Investigator and his/her staff 
prior to the entrance of the first subject to review study procedures and methods of recording 
findings in the eCRF. 
After enrollment of the first subject, an Endo Pharmaceuticals Inc. representative will be 
assigned to periodically monitor each Investigator site for study progress and to verify that 
standards of Good Clinical Practice (GCP) were followed. The Investigator is expected to 
prepare for the monitor visit, ensuring that all source documents, completed eCRFs, signed 
consent forms and other study related documents are readily available for review. 
19.3. 
Audits and Inspections 
The Investigator shall permit audits and inspections by the Sponsor, its representatives and 
members of regulatory agencies. The Investigator should immediately notify the Sponsor of an 
upcoming FDA or other regulatory agency inspection. 
19.4. 
Institutional Review Board (IRB) 
The Investigator shall permit members of the IRB/IEC to have direct access to source 
documents. 

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19.5. 
Data Recording and Documentation 
All data recordings and source documentation (including electronic health records) must be made 
available to the Sponsor (or designee), FDA and any other regulatory agencies that request 
access to study records, including source documents, for inspection and copying, in keeping with 
federal and local regulations. 
 

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20. 
QUALITY CONTROL AND QUALITY ASSURANCE 
Steps to assure the accuracy and reliability of data include the selection of qualified principal 
investigators and appropriate study centers, review of protocol procedures with the principal 
investigators and associated personnel prior to start of the study, and periodic monitoring visits 
conducted by the Sponsor or Sponsor representative. Significant and/or repeated non-compliance 
will be investigated and remedial action instituted when appropriate. Failure to comply with 
remedial actions may result in investigator site termination and regulatory authority notification. 
The Sponsor or its designee will utilize qualified monitors to review and evaluate activities 
conducted at Investigator Sites. 
The data will be entered into the clinical study database and verified for accuracy, following 
procedures defined by the Sponsor (or designee). Data will be processed and analyzed following 
procedures defined by the Sponsor (or designee). 
The study will be monitored and/or audited at intervals to ensure that the clinical study is 
conducted and data are generated, documented (recorded), and reported in compliance with the 
Study Protocol; International Conference on Harmonisation (ICH), E6 consolidated guidelines; 
and other applicable regulations. The extent, nature, and frequency of monitoring and/or audits 
will be based on such considerations as the study objectives and/or endpoints, the purpose of the 
study, study design complexity, and enrollment rate. At the conclusion of a program, a 
compliance statement will be generated by the Sponsor (or designee) listing all audit activities 
performed during the clinical study. 
 

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21. 
ETHICS 
21.1. 
Ethics Review 
Approval by the IRB/IEC prior to the start of the study will be the responsibility of the 
Investigator. A copy of approval documentation will be supplied to Endo Pharmaceuticals Inc. 
along with a roster of IRB members that demonstrates appropriate composition (a Department of 
Health and Human Services [DHHS] Assurance Number will satisfy this requirement). 
The study protocol, the informed consent form, advertisements, materials being provided to 
subjects and amendments (if any) will be approved to IRB/IECs at each study center in 
conformance with ICH E6, the Code of Federal Regulations (CFR), Title 21, Part 56 and any 
other applicable local laws. The Investigator is responsible for supplying the IRB/IEC with a 
copy of the current IB, Package Insert, or SPC as well as any updates issued during the study. 
During the course of the study, the Investigator will provide timely and accurate reports to the 
IRB/IEC on the progress of the study, at intervals not exceeding 1 year (or as appropriate), and 
will notify the IRB/IEC of SAEs or other significant safety findings, per the policy of the 
IRB/IEC. At the conclusion of the study, the Investigator will submit a final report or close out 
report to the IRB/IEC and provide a copy to Endo Pharmaceuticals Inc. 
Any amendment to this protocol will be provided to the Investigator in writing by Endo 
Pharmaceuticals Inc. No protocol amendment may be implemented (with the exceptions noted 
below) before it has been approved by the IRB and the signature page, signed by the 
Investigator, has been received by Endo Pharmaceuticals Inc. Where the protocol is amended to 
eliminate or reduce the risk to the subject, the amendment may be implemented before IRB 
review and approval. However, the IRB must be informed in writing of such an amendment and 
approval obtained within reasonable time limits. Deviating from the protocol is permitted only if 
absolutely necessary for the safety or clinical management of the subject, and must be 
immediately reported to Endo Pharmaceuticals Inc. 
The Investigator will be responsible for supplying updated safety and/or study information to 
study subjects as it becomes available. 
21.2. 
Ethical Conduct of the Study 
This clinical study is designed to comply with the ICH Guidance on General Considerations for 
Clinical Trials (62 FR 6611, December 17, 1997), Nonclinical Safety Studies for the Conduct of 
Human Clinical Trials for Pharmaceuticals (62 FR 62922, November 25, 1997), Good Clinical 
Practice: Consolidated Guidance (62 FR 25692, May 9, 1997) and 21 CFR parts 50, 54, 56 
and 312. 
The study will be conducted in full compliance with ICH E6, the FDA guidelines for GCP and in 
accordance with the ethical principles that have their origins in the Declaration of Helsinki 
defined in 21 CFR, 312.120. 

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21.3. 
Subject Information and Consent 
Subjects, after having the study explained to them and an opportunity to have their questions 
answered sufficiently, will give voluntary and written informed consent (in compliance with ICH 
E6, 4.8 and 21 CFR Parts 50 and 312) before participating in any study-related procedures. The 
consent shall be written in a language understandable to the subject. Subjects unable to read 
(illiterate) shall have the consent process performed in the presence of an independent witness 
who shall also sign the consent. Each subject will read, assent understanding, and sign an 
instrument of informed consent after having had an opportunity to discuss the study and consent 
documents with the Investigator before signing, and will be made aware that she may withdraw 
from the study at any time. 
In addition to obtaining informed consent/assent, the Investigator is responsible for obtaining any 
additional documentation to demonstrate compliance with local privacy laws applicable to 
activities performed. 
The consent/assent process shall be recorded in source documents. Signed copies of the informed 
consent and/or assent will be given to the Subject/LAR and originals will be placed in the 
Investigator study files. 
A unique Subject identification number will be assigned according to section 12.1.2.2 at the time 
that the Subject signs the informed consent form. 
 

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22. 
DATA HANDLING AND RECORDKEEPING 
22.1. 
Data Collection 
Endo will provide an electronic data capture (EDC) system for this study. Data collection will 
involve the use of an EDC system to which only authorized personnel will have access. The 
system will be secured to prevent unauthorized access to the data or the system. This will include 
the requirement for a user ID and password to enter or change data. The level of access to the 
EDC system will be dependent on the person’s role in the study. 
Study data will be collected from source documents and entered into an eCRF within the EDC 
system. The Investigator will be responsible for ensuring the eCRFs are completed in a timely 
manner relative to the subject’s visit. In addition to periodic monitoring occurring within the 
system by a Sponsor monitor, programmatic edit checks will be used to review EDC data for 
completeness, logic, and adherence to the study protocol. As a result of this monitoring and these 
checks, queries may be issued electronically to the clinical study sites and closed electronically 
by the monitor, data management staff or authorized staff at the study site. Additionally, the 
Investigator will review eCRFs, ensure all missing or corrected data is provided and will sign the 
eCRF pages with an electronic signature. 
An electronic audit trail will be maintained in the EDC system to track all changes made to data 
entered in the eCRF. Data will be retrievable in such a fashion that all information regarding 
each individual subject is attributable to that subject. Unless otherwise indicated, all data 
captured in the eCRF must first be captured in source documents. Data that can be directly 
recorded in the eCRF will be clearly identified in the section(s) of the protocol that describes the 
assessment(s). 
Data entries will be corrected by changing the entry in the EDC system. Any changes or 
corrections to eCRF data will be electronically tracked and will include the reason for correction, 
who made the correction and the date/time stamp when the correction was made within the audit 
trail of the EDC system. 
In addition, any contact with the subject via telephone or other means that provide significant 
clinical information must be documented in source documents as described above. 
22.2. 
Study Documentation 
Upon study completion, the Investigator will be provided with complete electronic copies of the 
case report form (CRF) data for his/her files. 

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23. 
REPORTING AND PUBLICATION 
All data generated in this study are the property of Endo Pharmaceuticals Inc. An integrated 
clinical and statistical report will be prepared at the completion of the study. 
Publication of the results by the Investigator will be subject to mutual agreement between the 
Investigator and Endo Pharmaceuticals Inc. 
 

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24. 
INVESTIGATOR OBLIGATIONS 
24.1. 
Regulatory Documents 
The Investigator is responsible for creating and/or maintaining all study documentation required 
by 21CFR 50, 54, 56 and 312, ICH, E6 section 8, as well as any other documentation defined in 
the protocol or the Investigator Agreement. The Investigator must maintain the documentation 
relating to this study and permit Endo Pharmaceuticals Inc. or a member of a regulatory agency 
access to such records. 
The Investigator must provide the following key documents to Endo Pharmaceuticals Inc. prior 
to the start of the study: 
• A completed and signed Form FDA 1572. If during the course of the study any 
information reported on the Form FDA 1572 changes, a revised Form FDA 1572 
must be completed and returned to Endo Pharmaceuticals Inc. for submission to the 
FDA. For studies executed outside the United States, documentation required by the 
governing regulatory authority may be substituted for the Form FDA 1572. 
• A fully executed contract 
• The Investigator’s Statement page in this protocol signed and dated by the 
Investigator and any subsequent amendment signature pages 
• The IB acknowledgment of receipt page 
• Curricula vitae for the Principal Investigator and all sub-Investigators listed on Form 
FDA 1572, including a copy of each physician’s license (if applicable) 
• A copy of the original IRB/IEC approval for conducting the study. If the study is 
ongoing, renewals must be submitted at yearly intervals or shorter intervals defined 
by the IRB/IEC. All subsequent modifications must be submitted and approved by the 
IRB, as described in section 21.1 
• A copy of the IRB/IEC-approved informed consent form 
• A list of IRB/IEC members or DHHS Assurance Number 
• Laboratory certifications and normal ranges (if local labs are required by the protocol) 
• A financial disclosure agreement completed and signed by the Investigator and all 
sub-Investigators listed on Form FDA 1572. Investigator site staff that submitted an 
initial financial disclosure are also responsible for informing Endo Pharmaceuticals 
Inc. of any changes to their initial financial disclosure form 1 year after the 
completion of the study 
A complete list of required regulatory documents will be supplied by Endo Pharmaceuticals Inc. 
or its representative. 

EN3835-303 Protocol Amendment 2 
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Page 110 
 
 
 
24.2. 
Delegation of Responsibilities and Adequate Resources 
The Investigator should have adequate time to conduct the study properly and should have an 
adequate number of qualified staff to assist with the conduct of the study. The Investigator shall 
delegate tasks only to individuals qualified by education, training and experience to perform the 
delegated tasks. The Investigator shall have direct oversight of all delegated activities and shall 
document delegation of responsibilities. The Investigator is responsible for ensuring all delegated 
staff have been properly trained on the protocol and their assigned study responsibilities. 
24.3. 
Medical Care of Study Subjects 
The Investigator and/or a qualified sub-Investigator shall be responsible for the subjects’ medical 
care. Any unrelated medical condition discovered during the course of the study should be 
communicated to the subject so that they may seek appropriate medical care. The Investigator 
will report all AEs as required by the protocol (section 14.5). The Investigator will inform study 
subjects of new information regarding the study drug as it becomes available. 
24.4. 
Use of Investigational Materials 
The Investigator will acknowledge that the study drug supplies are investigational and as such 
must be used strictly in accordance with the protocol and only under the supervision of the 
Principal Investigator or sub-Investigators listed on Form FDA 1572 (or other regulatory 
document, depending on region). Study drug must be stored in a safe and secure location. At 
study initiation, a representative from Endo Pharmaceuticals Inc. will inventory the study drug at 
the site. The Investigator must maintain adequate records documenting the receipt and 
disposition of all study supplies. Endo Pharmaceuticals Inc. or its representative will supply 
forms to document total inventory as well as subject specific accountability. The Investigator is 
responsible for monitoring subject’s use of the study drug to ensure compliance with the 
protocol. All study supplies shall be returned to Endo Pharmaceuticals Inc. or its designee. 
24.5. 
Retention of Records 
Federal and local regulations require that the Investigator retain a copy of all regulatory 
documents and records that support the data for this study (eg, informed consents, laboratory 
reports, source documents, study drug dispensing records) for whichever of the following is the 
longest period of time: 
• A period of 2 years following the final date of approval by the FDA or other 
regulatory agency of the study drug for the purposes that were the subject of the 
investigation; or 
• A period of 5 years following the date on which the results of the investigation were 
submitted to the FDA or other regulatory agency in support of, or as part of, an 
application for a research or marketing permit for the study drug for the purposes that 
were the subject of the investigation 
Endo Pharmaceuticals Inc. will notify Investigators once one of the above 2 timeframes has been 
satisfied. 

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If the investigation does not result in the submission of the data in support of, or as part of, an 
application for a research or marketing permit, records must be retained for a period of 2 years 
following notification by Endo Pharmaceuticals Inc. that the entire clinical investigation (not 
merely the Investigator’s portion) is completed, terminated, or discontinued or 2 years following 
withdrawal of the Investigational New Drug application (IND)/Clinical Trial Authorization 
(CTA) or request for marketing approval (New Drew Application [NDA]/Marketing 
Authorization Application [MAA]). 
If the Investigator retires, relocates, or for other reasons withdraws from the responsibility of 
keeping the study records, custody must be transferred to a person who will accept the 
responsibility. Endo Pharmaceuticals Inc. must be notified in writing of the name and address of 
the new custodian. Study records should not be destroyed without consultation with Endo 
Pharmaceuticals Inc. 
24.6. 
Subject Confidentiality 
All subject records submitted to Endo Pharmaceuticals Inc. or its designee will be identified only 
by initials and subject number. Subjects’ names are not to be transmitted to Endo 
Pharmaceuticals Inc. The Investigator will keep a Master Subject List on which the identification 
number and the full name, address, and telephone number of each subject are listed. It is the 
Investigators’ responsibility to inform study subjects that representatives of the Sponsor, FDA, or 
other regulatory agencies may review all records that support their participation in the study. The 
Investigator will adhere to all privacy laws to which he/she is subject. 
 

EN3835-303 Protocol Amendment 2 
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25. 
TERMINATION OF STUDY 
The Sponsor has the right to suspend or terminate the study at any time. The study may be 
suspended or terminated for any reason. 
 

EN3835-303 Protocol Amendment 2 
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26. 
INVESTIGATOR’S STATEMENT 
I agree to conduct the study in accordance with the protocol, and with all applicable government 
regulations and Good Clinical Practice guidance. 
 
 
 
_____/_____/______ 
Investigator’s Signature 
Date 
 
 
 
Typed Name of Investigator 
 

EN3835-303 Protocol Amendment 2 
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Page 114 
 
 
 
27. 
REFERENCES 
1. Khan MH, Victor F, Rao B, Sadick NS. Treatment of cellulite: Part I. Pathophysiology. 
J Am Acad Dermatol 2010;62(3):361-70. 
2. Hexsel D, de Oliveira Dal’Forno T, Mazzuco R. Definition, clinical aspects, 
classifications, and diagnostic techniques. In: Goldman MP, Hexsel D, eds. Cellulite: 
Pathophysiology and Treatment. 2nd ed. New York, NY: Informa Healthcare; 
2010:13-21. 
3. Rawlings AV. Cellulite and its treatment. Int J Cosmetic Sci. 2006;28(3):175-90. 
4. Terranova F, Berardesca E, Maibach H. Cellulite: nature and aetiopathogenesis. Int J 
Cosmetic Sci. 2006;28(3):157-67. 
5. Avram MM. Cellulite: a review of its physiology and treatment. J Cosmet Laser Ther. 
2004;6(4):181-5. 
6. Khan MH, Victor F, Rao B, Sadick NS. Treatment of cellulite: Part II. Advances and 
controversies. J Am Acad Dermatol 2010;62(3):373-84. 
7. Collis N, Elliot LA, Sharpe C, Sharpe DT. Cellulite treatment: a myth or reality: a 
prospective randomized, controlled trial of two therapies, endermologie and 
aminophylline cream. Plast Reconstr Surg. 1999;104(4):1110-4. 
8. Hexsel DM, Mazzuco R. Subcision: a treatment for cellulite. Int J Dermatol. 
2000;39(7):539-44. 
9. Boyce S, Pabby A, Chuchaltkaren P, Brazzini B, Goldman MP. Clinical evaluation of a 
device for the treatment of cellulite: Triactive. Am J Cosmet Surg. 2005;22:233-7. 
10. DiBernardo BE. Treatment of cellulite using a 1440-nm pulsed laser with one-year 
follow-up. Aesthet Surg J. 2011;31(3):328-41. 
11. Investigational Brochure: Collagenase Clostridium Histolyticum for Injection 
(AA4500/EN3835), Version 8.0. Endo Pharmaceuticals Inc.; July 2017. 
 

EN3835-303 Protocol Amendment 2 
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APPENDIX A. DOCUMENTS REQUIRED PRIOR TO INITIATION OF 
THE STUDY 
As a sponsor of a clinical study, Endo Pharmaceuticals Inc. has an obligation to ensure that the 
study will be conducted by a qualified Investigator with sufficient resources of time, personnel, 
and physical facilities to conduct the study and to ensure that the Investigator understands and 
agrees to comply with the protocol, applicable regulations, policies, and procedures. The 
following documentation is required: 
From the Principal Investigator 
1. A signed agreement to perform the study per protocol (the signature page will suffice). 
2. A signed Letter of Financial Agreement (including confidentiality statement). 
3. Name(s) of the Principal Investigator and of all sub-Investigator(s) 
4. All address(es) of the clinical site(s). 
5. A current medical license valid where he/she practices and a current curriculum vitae for 
the Principal Investigator (signed and dated) and all sub-Investigators, to contain at least 
the following elements: 
a. For physicians: 
i. Date of degree in Medicine 
ii. Name of the Institution granting the degree in Medicine 
iii. Previous clinical postings with dates 
b. For non-physician allowed by national law or regulations to act as clinical 
Investigators: 
i. Date and description of most advanced degree 
ii. Name of the Institution granting the degree in number (i) 
iii. Other accreditation or qualifications relevant to the study 
iv. Previous postings with dates 
v. Name and qualification (see 5a above) of the physician or dentist in charge of 
study subjects 
Note: If a non-physician is serving as Principal Investigator, then a qualified physician 
must be assigned as a sub-Investigator for the trial, to be responsible for all trial-related 
medical decisions. 
6. Written notification of Institutional Review Board/Independent Ethics Committee/Human 
Research Ethics Committee (IRB/IEC/HREC) approval. The minimum requirements are 
as follows: 
a. Dated letter, including: 
i. The date on which the meeting for the review of the study protocol took place 
ii. Study protocol/amendment number, and version date 

EN3835-303 Protocol Amendment 2 
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iii. A clear statement of approval of the protocol and the informed consent text with 
version date, and authorization for the study to proceed 
iv. If the Investigator or any sub-Investigator is a part of the IRB/IEC/HREC 
Review Board, assurance that the Investigator abstained from voting at the 
meeting(s) when the study was discussed. 
b. A dated list of the members and their occupations 
c. A specimen copy of the Committee-approved informed consent text to be used in the 
study 
7. Food and Drug Administration (FDA) Form 1572 (for studies submitted under a US 
Investigational New Drug application [IND]). 
8. Financial Disclosure Certification or Certification of Non-Disclosure (for studies to be 
submitted for a US New Drug Application/Biologics License Application [NDA/BLA]). 
Other 
Any other documentation required by national law or regulations to be in the possession of the 
sponsor or the Investigator for study participation or study initiation. 

EN3835-303 Protocol Amendment 2 
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Page 117 
 
 
 
APPENDIX B. PATIENT-REPORTED PHOTONUMERIC CELLULITE SEVERITY SCALE (PR-PCSS) 
FOR THE BUTTOCK 
 
 

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Page 118 
 
 
 
APPENDIX C. CLINICIAN-REPORTED PHOTONUMERIC CELLULITE SEVERITY SCALE 
(CR-PCSS) FOR THE BUTTOCK 
 

EN3835-303 Protocol Amendment 2 
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Page 119 
 
 
 
APPENDIX D. PATIENT REPORTED CELLULITE IMPACT SCALE 
(PR-CIS) 
Please select the rating that best represents your answer on a scale of 0 to 10 with 0 representing 
“Not at all” and 10 representing “Extremely” while viewing digital images of your buttocks. 
Please answer each question. 
1. Thinking about the areas selected for treatment, how happy are you with the appearance of 
your cellulite? 
Not at all 
 
 
 
 
 
 
 
 
 
Extremely 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
2. Thinking about the areas selected for treatment, how bothered are you by the appearance of 
your cellulite? 
Not at all 
 
 
 
 
 
 
 
 
 
Extremely 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
3. Thinking about the areas selected for treatment, how self-conscious are you about the 
appearance of your cellulite? 
Not at all 
 
 
 
 
 
 
 
 
 
Extremely 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
4. Thinking about the areas selected for treatment, how embarrassed are you about the 
appearance of your cellulite? 
Not at all 
 
 
 
 
 
 
 
 
 
Extremely 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
5. Thinking about the areas selected for treatment, how much older do you look because of your 
cellulite? 
Not at all 
 
 
 
 
 
 
 
 
 
Extremely 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
6. Thinking about the areas selected for treatment, how overweight or out of shape do you look 
because of your cellulite? 
Not at all 
 
 
 
 
 
 
 
 
 
Extremely 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 

Protocol 
 
 
 
 
Endo Pharmaceuticals Inc. 
1400 Atwater Drive 
Malvern, PA 19355 USA 
 
EN3835 
EN3835-303 
A PHASE 3, RANDOMIZED, DOUBLE-BLIND, 
PLACEBO-CONTROLLED STUDY OF EN3835 IN THE 
TREATMENT OF EDEMATOUS FIBROSCLEROTIC 
PANNICULOPATHY 
IND 110077 
 
Amendment 1 
 
Date: 
Original Protocol:  September 27, 2017 
Amendment 1: December 19, 2017 
 
 
Auxilium Pharmaceuticals, Inc. (Auxilium) was acquired by Endo International plc. in 
January 2015. The sponsor of the application remains as Auxilium Pharmaceuticals, LLC, 
1400 Atwater Drive, Malvern, PA; however, Endo Pharmaceuticals Inc. is authorized to act and 
to communicate on behalf of Auxilium. 
 
 
Confidentiality Statement 
This document is the property of Endo Pharmaceuticals Inc. and may not—in full or part—be 
passed on, reproduced, published, distributed to any person, or submitted to any regulatory 
authority without the express written permission of Endo Pharmaceuticals Inc. 

EN3835-303 Protocol Amendment 1 
19-Dec-2017 
Endo Pharmaceuticals Inc. 
Page 3 
 
 
 
Section 
Original Text 
Revised Text 
4., Synopsis, 
Diagnosis and 
Inclusion/ 
Exclusion 
Criteria, 
Exclusion 
Criteria  
2. Has any of the following local conditions 
in the areas to be treated: 
a. History of lower extremity thrombosis or 
post-thrombosis syndrome 
b. Vascular disorder (eg, varicose veins, 
telangiectasia) in area to be treated 
c. Inflammation or active infection 
d. Active cutaneous alteration including rash, 
eczema, psoriasis, or skin cancer 
e. Has a tattoo and/or a mole located within 
2 cm of the site of injection  
2. Has any of the following local conditions 
in the areas to be treated: 
a. History of lower extremity thrombosis or 
post-thrombosis syndrome 
b. Vascular disorder (eg, varicose veins, 
telangiectasia) in area to be treated 
c. Inflammation or active infection 
d. Severe skin laxity, flaccidity, and/or 
sagging  
e. Active cutaneous alteration including rash, 
eczema, psoriasis, or skin cancer 
f. Has a tattoo and/or a mole located within 
2 cm of the site of injection 
4., Synopsis, 
Criteria for 
Evaluation, 
Efficacy 
Added text 
 Patient Reported Cellulite Impact Scale: 6 
questions with responses to each question 
consisting of a numerical rating scale 
(NRS) ranging from 0 (Not at all) to 10 
(Extremely) 
4., Synopsis, 
Statistical 
Methods, 
Analysis, 
Supportive 
Endpoints 
Added text 
 Change from baseline (Day 1) of the 
PR-CIS total score at Day 71 
 Change from baseline (Day 1) of the 
abbreviated PR-CIS score at Day 71 
 Proportion of subjects with a change from 
baseline (Day1) of the PR-CIS ≥12 at 
Day 71 
 Proportion of subjects with a change from 
baseline (Day 1) of the abbreviated PR-CIS 
≥10 at Day 71 
5., Schedule of 
Events, Physical 
examination 
Day -14 to -1 Screening: X 
Day 71 (+ 5d)/End of Study/Early 
Termination: X 
Day -14 to -1 Screening: X 
5., Schedule of 
Events, Subject 
cellulite 
assessments, 
Patient Reported 
Cellulite Impact 
Scale (PR-CIS) 
Added table row 
 Patient Reported Cellulite Impact Scale 
(PR-CIS) 
Day 1 Treatment Visit 1: Xc,g 
Day 71 (+ 5d)/End of Study/Early 
Termination: Xg 
5., Schedule of 
Events, 
Investigator 
cellulite 
assessments, 
Hexsel Cellulite 
Severity Scale 
(CSS) 
 Hexsel Cellulite Severity Scale (CSS) 
Day -14 to -1 Screening: Xb,i 
Day 1 Treatment Visit 1: Xc,b,i 
Deleted table row 

EN3835-303 Protocol Amendment 1 
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Endo Pharmaceuticals Inc. 
Page 4 
 
 
 
Section 
Original Text 
Revised Text 
5., Schedule of 
Events, Table 
footnotes 
i Initial Hexsel CSS at Screening must be ≤13 
on each of 2 bilateral buttocks and the 
buttocks must again be ≤13 at Day 1 visit  
Deleted text 
j Before randomization, each of the subject’s 
buttocks must have ratings of 3 or 4 (moderate 
or severe) in both the CR-PCSS and 
PR-PCSS, and Hexsel CSS score ≤13. 
i Before randomization, each of the subject’s 
buttocks must have ratings of 3 or 4 (moderate 
or severe) in both the CR-PCSS and 
PR-PCSS. 
7., List of 
Abbreviations, 
Table 2: 
Abbreviations 
and Special 
Terms 
CSS: Cellulite severity scale 
Deleted table row 
Added table row 
PR-CIS: Patient Reported Cellulite Impact 
Scale 
11.1., Subject 
Inclusion Criteria 
3. At Screening visit, have 2 bilateral 
buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as 
reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as 
reported by the Investigator (CR-PCSS), 
and 
c. a Hexsel CSS score no greater than 13 
3. At Screening visit, have 2 bilateral 
buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as 
reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as 
reported by the Investigator (CR-PCSS) 
4. At Day 1 visit, have 2 bilateral buttocks 
with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as 
reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as 
reported by the Investigator (CR-PCSS), 
and 
c. a Hexsel CSS score no greater than 13 
4. At Day 1 visit, have 2 bilateral buttocks 
with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as 
reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as 
reported by the Investigator (CR-PCSS)  
11.2., Subject 
Exclusion 
Criteria 
2. Has any of the following local conditions 
in the areas to be treated: 
a. History of lower extremity thrombosis or 
post-thrombosis syndrome 
b. Vascular disorder (eg, varicose veins, 
telangiectasia) in area to be treated 
c. Inflammation or active infection 
d. Active cutaneous alteration including rash, 
eczema, psoriasis, or skin cancer 
e. Has a tattoo and/or a mole located within 2 
cm of the site of injection 
2. Has any of the following local conditions 
in the areas to be treated: 
a. History of lower extremity thrombosis or 
post-thrombosis syndrome 
b. Vascular disorder (eg, varicose veins, 
telangiectasia) in area to be treated 
c. Inflammation or active infection 
d. Severe skin laxity, flaccidity, and/or 
sagging 
e. Active cutaneous alteration including rash, 
eczema, psoriasis, or skin cancer 
f. Has a tattoo and/or a mole located within 
2 cm of the site of injection 

EN3835-303 Protocol Amendment 1 
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Endo Pharmaceuticals Inc. 
Page 5 
 
 
 
Section 
Original Text 
Revised Text 
12.1.2.2., 
Screening Period 
(Day -14 to 
Day -1) 
5. Prior to Investigator CR-PCSS or Hexsel 
CSS assessment, subjects will rate each of 
their two buttocks using the PR-PCSS 
while viewing their digital images (section 
13.1.2.1); the Investigator is blinded to 
these scores 
5. Prior to Investigator CR-PCSS assessment, 
subjects will rate each of their two buttocks 
using the PR-PCSS while viewing their 
digital images (section 13.1.2.1); the 
Investigator is blinded to these ratings 
6. After the subject has completed the 
PR-PCSS ratings, the Investigator will 
conduct live assessments of subject’s 
cellulite severity of each of the two 
buttocks using the CR-PCSS (section 
13.1.2.4); the subject is blinded to these 
ratings 
7. After the Investigator has completed the 
CR-PCSS ratings, the Investigator will 
conduct live evaluation of each of the two 
buttocks using the Hexsel CSS; the subject 
is blinded to these ratings. The ratings from 
the PR-PCSS, CR-PCSS, and Hexsel CSS 
(section 13.1.2.6) will be used to assess 
initial eligibility of the buttocks for study 
entry 
6. After the subject has completed the 
PR-PCSS ratings, the Investigator will 
conduct live assessments of subject’s 
cellulite severity of each of the two 
buttocks using the CR-PCSS (section 
13.1.2.5); the subject is blinded to these 
ratings. The ratings from the PR-PCSS and 
CR-PCSS will be used to assess initial 
eligibility of the buttocks for study entry 
12.2., Selecting 
and Marking 
Dimples during 
Treatment Visits 
The cellulite severity assessments using the 
PR-PCSS, CR-PCSS, and Hexsel CSS (note 
that the Hexsel CSS assessment is performed 
at Screening visit and Day 1 visit only) will be 
completed prior to marking dimples and 
injection sites. 
The cellulite severity assessments using the 
PR-PCSS and CR-PCSS will be completed 
prior to marking dimples and injection sites. 
12.4.1., 
Treatment Visit 
1: Pre-Injection 
4. Subjects will rate each of their buttocks 
using the PR-PCSS (section 13.1.2.1); the 
Investigator is blinded to these scores 
4. Subjects will rate each of their buttocks 
using the PR-PCSS (section 13.1.2.1); the 
Investigator is blinded to these ratings 
Added text 
5. Subjects will complete the Patient 
Reported Cellulite Impact Scale 
assessment (PR-CIS; section 13.1.2.3): the 
Investigator is blinded to this rating 
5. The Investigator will conduct live 
assessments of subject’s cellulite severity 
of each of the buttocks using the CR-PCSS 
(section 13.1.2.4); the subject is blinded to 
these ratings 
6. The Investigator will conduct live cellulite 
evaluation of each of the buttocks using the 
Hexsel CSS. The ratings from the PR-
PCSS, CR-PCSS and Hexsel CSS 
(section 13.1.2.6) will be used to assess 
eligibility for randomization 
6. The Investigator will conduct live 
assessments of subject’s cellulite severity 
of each of the buttocks using the CR-PCSS 
(section 13.1.2.5); the subject is blinded to 
these ratings. The ratings from the 
PR-PCSS and CR-PCSS will be used to 
assess eligibility for randomization 

EN3835-303 Protocol Amendment 1 
19-Dec-2017 
Endo Pharmaceuticals Inc. 
Page 6 
 
 
 
Section 
Original Text 
Revised Text 
7. Subjects with PR-PCSS or CR-PCSS 
ratings in either of the buttocks <3 or a 
Hexsel CSS total score in either of the 
buttocks greater than 13 (section 13.1.2.6) 
will be excluded from participation 
7. Subjects with PR-PCSS or CR-PCSS 
ratings in either of the buttocks <3 will be 
excluded from participation 
8. Randomization of subjects with two 
buttocks eligible for treatment (eligible 
criteria being each buttock have PR-PCSS 
and CR-PCSS scores of 3 or 4 and a 
Hexsel CSS total score not greater than 13) 
to treatment (section 12.10); obtain kit 
numbers of study treatment 
8. Randomization of subjects with two 
buttocks eligible for treatment (eligible 
criteria being each buttock have PR-PCSS 
and CR-PCSS scores of 3 or 4) to 
treatment (section 12.10); obtain kit 
numbers of study treatment 
12.6., Day 71 
(+5 days)/End of 
Study/Early 
Termination 
6. Subject Cellulite Assessment of each of the 
two buttocks using the photographic image 
before marking dimples and injection sites 
(NOTE: complete subject cellulite 
assessments before Investigator cellulite 
assessments) using: 
a. Patient Reported Photonumeric Cellulite 
Severity Scale (PR-PCSS) assessment 
(section 13.1.2.1) 
b. Subject Global Aesthetic Improvement 
Scale (S-GAIS) (section 13.1.2.2) 
c. Subject Satisfaction with Cellulite 
Treatment Assessment (section 13.1.2.3); 
note this assessment is of both left and 
right buttocks rather than each individual 
buttock 
6. Subject Cellulite Assessment of each of the 
two buttocks using the photographic image 
before marking dimples and injection sites 
(NOTE: complete subject cellulite 
assessments before Investigator cellulite 
assessments) using: 
a. Patient Reported Photonumeric Cellulite 
Severity Scale (PR-PCSS) assessment 
(section 13.1.2.1) 
b. Subject Global Aesthetic Improvement 
Scale (S-GAIS) (section 13.1.2.2) 
c. Patient Reported Cellulite Impact Scale 
(PR-CIS assessment (section 13.1.2.3); 
note this assessment is of both left and 
right buttocks rather than each individual 
buttock 
d. Subject Satisfaction with Cellulite 
Treatment Assessment (section 13.1.2.4); 
note this assessment is of both left and 
right buttocks rather than each individual 
buttock 
12.10., Blinding 
and 
Randomization 
On Day 1, if each of the buttocks again meet 
the criteria (3 or 4 on the PR-PCSS and 
CR-PCSS and no greater than 13 on Hexsel 
CSS) the subject will be randomized to a 
treatment group. 
On Day 1, if each of the buttocks again meet 
the criteria (3 or 4 on the PR-PCSS and 
CR-PCSS) the subject will be randomized to a 
treatment group. 

EN3835-303 Protocol Amendment 1 
19-Dec-2017 
Endo Pharmaceuticals Inc. 
Page 7 
 
Section 
Original Text 
Revised Text 
13.1.2.3, Patient 
Reported 
Cellulite Impact 
Scale (PR-CIS) 
Added section 
13.1.2.3. Patient Reported Cellulite Impact 
Scale (PR-CIS) 
At the Day 1 visit and Day 71 visit, subjects 
will be instructed to answer 6 questions related 
to the areas selected for treatment on their 
buttocks on the Patient Reported Cellulite 
Impact Scale (Appendix D) while viewing 
digital images of their buttocks. The PR-CIS 
assesses the visual and emotional impact of 
cellulite (happy, bothered, self-conscious, 
embarrassed, looking older or looking 
overweight or out of shape) using a 6-question 
survey, with each question rated on a 
numerical rating scale from 0 (not at all) to 10 
(extremely). 
This variable will be entered directly into the 
EDC system, thus the electronic database will 
serve as the direct point of data capture and 
will serve as source for this variable. 
13.1.2.4, Subject 
Satisfaction  
Added text 
This variable will be entered directly into the 
EDC system, thus the electronic database will 
serve as the direct point of data capture and 
will serve as source for this variable. 
13.1.2.6, Hexsel 
Cellulite Severity 
Scale 
13.1.2.6. Hexsel Cellulite Severity Scale 
The Hexsel Cellulite Severity Scale (referred 
to as the Hexsel CSS) is a photonumeric scale 
that looks at 5 key morphologic features of 
cellulite: (A) number of evident depressions, 
(B) depth of depressions, (C) morphological 
appearance of skin surface alterations, (D) 
laxity, flaccidity or sagging of skin, and (E) 
current classification scale based on medical 
literature including Nürnberger and 
Müller.(12,13) Each of these features is 
evaluated on a 4-point scale from a low of 0 to 
a high of 3 as described in Table 8. The total 
score is the summation of all 5 features 
(Appendix D). 
Deleted section and table 

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Section 
Original Text 
Revised Text 
APPENDIX E. 
REFERENCE 
IMAGES FOR 
HEXSEL 
SEVERITY 
RATINGS 
APPENDIX E. REFERENCE IMAGES FOR 
HEXSEL SEVERITY RATINGS  
The 2 images below are representative of a 
Hexsel score of 13, the maximum severity 
level to be included in the study. Subjects with 
cellulite severity that exceeds a Hexsel score 
of 13 should be excluded. 
[Image 1] [Image 2] 
The image below represents a Hexsel score 
>13, and depicts excessive skin laxity in the 
buttock and posterolateral thigh. Subjects with 
a Hexsel score >13 should be excluded from 
the study. 
[Image 3] 
Deleted appendix and images 

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4. 
SYNOPSIS 
Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
Title of Study: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of EN3835 in the 
Treatment of Edematous Fibrosclerotic Panniculopathy 
Lead Principal Investigator: 
Study Period:  
Estimated date first subject enrolled:  
Feb-2018 
Estimated date last subject completed:  
Sep-2018 
Phase of Development: 3 
Objectives:  
To assess the efficacy and safety of EN3835 in the treatment of edematous fibrosclerotic panniculopathy 
(EFP), commonly known as cellulite, in adult women  
Study Design: This study is a Phase 3 randomized, double-blind, placebo-controlled study of the 
efficacy and safety of EN3835 in the treatment of EFP in adult women. Subjects will be screened for 
study eligibility within 14 days prior to enrolling in this study. Subjects with 2 treatment areas (bilateral 
buttocks) (also referred to as quadrants) with moderate or severe levels of cellulite as independently 
assessed by the subject using the Patient Reported Photonumeric Cellulite Severity Scale (PR-PCSS) 
and by the Investigator using the Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 
will be eligible. The eligibility of the buttocks will be confirmed on Day 1. 
Once the eligibility of the buttocks is confirmed, subjects will be randomly assigned to a treatment 
group (EN3835 0.84 mg per buttock or placebo) in a 1:1 ratio within an investigational site. Each 
subject will receive a treatment course which consists of up to 3 treatment visits (sessions), separated by 
21 days (ie, Days 1, 22, and 43). Each treatment visit will consist of 12 injections (0.3 mL per injection 
of EN3835 0.07 mg/injection or placebo; 0.84 mg in 3.6 mL per buttock) in each of the two buttocks for 
a total volume of 7.2 mL (1.68 mg). Selection of dimples to be treated in the buttocks will be at the 
discretion of the Investigator. End of study will occur at study day 71.  
At each treatment visit, each of the buttocks will be photographed before and after marking dimples and 
injection sites while the subject is in a consistent, standardized relaxed standing pose. The subject will 
assess the digital photographic image (pre-marking) of each of the buttocks using the PR-PCSS to 
determine the severity of EFP in each of the buttocks. In addition, the subject will evaluate each of the 
buttocks using a Subject Global Aesthetic Improvement Scale (S-GAIS). Subsequently, the Investigator 
will conduct live assessments of each buttock using the CR-PCSS. At Day 1, the subject will complete a 
Patient Reported Cellulite Impact Scale (PR-CIS) assessment. The subject assessments will always be 
completed prior to and independently of the Investigator assessments at each treatment visit. In addition, 
the Investigator will assess each of the buttocks using an Investigator Global Aesthetic Improvement 
Scale (I-GAIS). All of the assessments must be done before the dimple marking. 
At Day 71 (End of Study/Early Termination), photographs of each of the buttocks will be taken and 
evaluated by subject using the PR-PCSS. The Investigator will conduct live assessments of each of the 
buttocks using the CR-PCSS. Global assessment evaluations will be completed by both the subject and 
the Investigator. 
Number of Subjects (Planned): 420 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
Study Center(s): Approximately 25 sites in United States 
Diagnosis and Inclusion/Exclusion Criteria: 
Inclusion Criteria: 
1. Voluntarily sign and date an informed consent agreement 
2. Be a female ≥18 years of age 
3. At Screening visit, have 2 bilateral buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as reported by the Investigator (CR-PCSS) 
4. At Day 1 visit, have 2 bilateral buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as reported by the Investigator (CR-PCSS) 
5. Be willing to apply sunscreen to the buttocks before each exposure to the sun while participating 
in the study (ie, Screening through end of study) 
6. Be judged to be in good health, based upon the results of a medical history, physical 
examination, and laboratory profile at Screening  
7. Have a negative serum pregnancy test at Screening and a negative urine pregnancy test before 
injection of study drug and be using a stable and effective contraception method (eg, abstinence, 
intrauterine device [IUD], hormonal [estrogen/progestin] contraceptives, or double barrier 
method) for at least 1 menstrual cycle prior to study enrollment and for the duration of the 
study; or be menopausal defined as 12 months of amenorrhea in the absence of other biological 
or physiological causes, as determined by the Investigator; or post-menopausal for at least 
1 year; or be surgically sterile  
8. Be willing and able to cooperate with the requirements of the study 
9. Be able to read, complete and understand the patient-reported outcomes rating instruments in 
English 
Exclusion Criteria: 
A subject will be excluded from study participation if she: 
1. Has any of the following systemic conditions: 
a. Coagulation disorder 
b. Evidence or history of malignancy (other than excised basal-cell carcinoma) unless there 
has been no recurrence in at least 5 years 
c. History of keloidal scarring or abnormal wound healing 
d. Concurrent diseases or conditions that might interfere with the conduct of the study, 
confound the interpretation of the study results, or endanger the subject’s well-being. Any 
questions about concurrent diseases should be discussed with the Medical Monitor 
e. Evidence of clinically significant abnormalities on physical examination, vital signs, 
electrocardiogram (ECG), or clinical laboratory values 
2. Has any of the following local conditions in the areas to be treated: 
a. History of lower extremity thrombosis or post-thrombosis syndrome 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
b. Vascular disorder (eg, varicose veins, telangiectasia) in area to be treated 
c. Inflammation or active infection  
d. Severe skin laxity, flaccidity, and/or sagging  
e. Active cutaneous alteration including rash, eczema, psoriasis, or skin cancer 
f. Has a tattoo and/or a mole located within 2 cm of the site of injection  
3. Requires the following concomitant medications before or during participation in the trial: 
a. Anticoagulant or antiplatelet medication or has received anticoagulant or antiplatelet 
medication (except for ≤150 mg aspirin daily) within 7 days before injection of study drug 
4. Has used any of the following for the treatment of EFP on a buttock within the timelines 
identified below or intends to use any of the following at any time during the course of the 
study: 
a. Liposuction in a buttock during the 12-month period before injection of study drug 
b. Injections (eg, mesotherapy); radiofrequency device treatments; laser treatment; buttock 
implant treatment; cryolipolysis; or surgery (including subcision and/or powered subcision) 
within a buttock during the 12-month period before injection of study drug 
c. Any investigational treatment for EFP on a buttock during the 12-month period before 
injection of study drug 
d. Endermologie™ or similar treatments within a buttock during the 6-month period before 
injection of study drug 
e. Massage therapy within a buttock during the 3-month period before injection of study drug 
f. Creams (eg, Celluvera™, TriLastin®) and/or home therapies to prevent or mitigate EFP 
within a buttock during the 2-week period before injection of study drug 
5. Is presently nursing or providing breast milk 
6. Intends to become pregnant during the study 
7. Intends to initiate an intensive sport or exercise program during the study 
8. Intends to initiate a weight reduction program during the study 
9. Intends to use tanning spray or tanning booths during the study 
10. Has received an investigational drug or treatment within 30 days before injection of study drug 
11. Has a known systemic allergy to collagenase or any other excipient of study drug 
12. Has received any collagenase treatments at any time prior to treatment 
13. Was a subject in a previous cellulite clinical trial of collagenase clostridium histolyticum 
(CCH): AUX-CC-830, AUX-CC-831, EN3835-102, EN3835-104, EN3835-201, and/or 
EN3835-202 
14. Any other condition(s) that, in the Investigator’s opinion, might indicate the subject to be 
unsuitable for the study 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
Investigational Product, Dosage and Mode of Administration: EN3835, 1.68 mg, subcutaneous. A 
dose of 0.84 mg of EN3835 per buttock will be administered as 12 subcutaneous injections (0.3-mL 
injection administered as three 0.1-mL aliquots per injection) in each of two buttocks for a total dose of 
1.68 mg and a total volume of 7.2 mL (3.6 mL per buttock). Total number of injections will be 
24 injections per treatment visit into the two buttocks. There will be 3 treatment visits at 21 days 
intervals, ie, treatments on Days 1, 22, and 43 will be administered. 
Duration of Study: Approximately 84 days (includes screening phase) 
Screening Phase: Up to 14 days 
Criteria for Evaluation: 
Efficacy: 
 
Subject using PR-PCSS while viewing digital image of the left buttock: 5-level scale 
ranging from 0 (no cellulite) to 4 (severe cellulite) (Day 1 (Baseline) and Days 22, 43, and 
71) for the left buttock 
 
Subject using PR-PCSS while viewing digital image of the right buttock: 5-level scale 
ranging from 0 (no cellulite) to 4 (severe cellulite) (Day 1 (Baseline) and Days 22, 43, and 
71) for the right buttock 
 
Investigator using the CR-PCSS by live assessment: 5-level scale ranging from 0 (no 
cellulite) to 4 (severe cellulite) (Day 1 (Baseline) and Days 22, 43, and 71) for the left 
buttock 
 
Investigator using the CR-PCSS by live assessment: 5-level scale ranging from 0 (no 
cellulite) to 4 (severe cellulite) (Day 1 (Baseline) and Days 22, 43, and 71) for the right 
buttock 
 
Investigator Global Aesthetic Improvement Scale (I-GAIS): 7-level scale ranging from 3 
(very much improved) to −3 (very much worse) (Days 22, 43, and 71) for the left buttock 
 
Investigator Global Aesthetic Improvement Scale (I-GAIS): 7-level scale ranging from 3 
(very much improved) to −3 (very much worse) (Days 22, 43, and 71) for the right buttock 
 
Subject Global Aesthetic Improvement Scale (S-GAIS): 7-level scale ranging from 3 (very 
much improved) to −3 (very much worse) (Days 22, 43, and 71) for the left buttock 
 
Subject Global Aesthetic Improvement Scale (S-GAIS): 7-level scale ranging from 3 (very 
much improved) to −3 (very much worse) (Days 22, 43, and 71) for the right buttock 
 
Patient Reported Cellulite Impact Scale: 6 questions with responses to each question 
consisting of a numerical rating scale (NRS) ranging from 0 (Not at all) to 10 (Extremely) 
 
Subject satisfaction with cellulite treatment assessment: 5-level scale ranging from 2 (very 
satisfied) to −2 (very dissatisfied) (Day 71) for both left and right buttocks 
Safety: 
Safety will be assessed throughout the study through the recording of: 
 
Adverse events (AEs) (including those of special interest (AESI); which are adverse events 
such as bruising, ecchymosis, hematomas, and contusions that occur remote to the site of 
drug administration, or any hypersensitivity reactions, including anaphylaxis) 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
Analyses:  
Analyses of Primary Endpoint: 
The primary endpoint is the proportion of 2-level composite responders at Day 71 defined as subjects 
with at least one of two treated buttocks with: 
 
an improvement in severity from baseline (Day 1 visit) of at least 2 levels of severity in the 
CR-PCSS as assessed live by the Investigator, and 
 
an improvement in severity from baseline of at least 2 levels of severity in the PR-PCSS as 
assessed by the subject while viewing the digital image of the same buttock. 
A subject will be considered a responder if these criteria are met in the left buttock or right buttock or 
both buttocks in that subject. 
The primary endpoint will be summarized as percentages and analyzed using a Cochran-Mantel-
Haenszel test that compares the 2 treatment groups and adjusts for Investigator at a level of significance 
of 0.05. The ITT population will be evaluated for the primary endpoint with any subject not having an 
evaluation of CR-PCSS and/or PR-PCSS at Day 71 classified as a non-responder. 
Sensitivity analyses for the primary endpoint will include: 
 
ITT subjects with missing data handled by multiple imputation (MI) approach 
 
ITT subjects with missing data handled by a last observation carried forward (LOCF) 
approach 
 
mITT subjects with missing data handled by an LOCF approach 
 
Observed data only (no missing data imputed) 
 
Per-protocol (PP) subjects with missing data handled by an LOCF approach if 10% or more 
subjects are excluded in the PP population from mITT population. 
Analyses of Key Secondary Endpoints:  
There will be 4 key secondary endpoints grouped as two families of 2 endpoints per family analyzed in a 
hierarchical order. 
 
Family #1 – two endpoints: 
- 
Proportion of 1-level PR-PCSS responders defined as subjects with ≥1-level 
improvement in PR-PCSS severity rating of left buttock at Day 71 compared to Day 1 
- 
Proportion of 1-level PR-PCSS responders defined as subjects with ≥1-level 
improvement in PR-PCSS severity rating of right buttock at Day 71 compared to Day 1 
 
Family #2 – two endpoints: 
- 
Proportion of 1-level S-GAIS responders defined as subjects with ≥1-level 
improvement (improved, much improved or very much improved) in the S-GAIS 
assessment of left buttock at Day 71 
- 
Proportion of 1-level S-GAIS responders defined as subjects with ≥1-level 
improvement (improved, much improved or very much improved) in the S-GAIS 
assessment of right buttock at Day 71 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
The key secondary efficacy analyses will be analyzed in the same manner as the primary endpoint based 
on the ITT population. The family #1 key secondary efficacy analyses will be performed only if the 
primary efficacy analysis is significant at a significance level of p ≤ 0.05 (gatekeeping strategy). 
Similarly, family #2 key secondary efficacy analyses will be performed only if at least one of the key 
secondary efficacy endpoints of family #1 is significant at a significance level of p ≤ 0.025 (parallel 
gatekeeping strategy). Within a family of key secondary efficacy endpoints, Bonferroni method will be 
performed to relocate unused alpha for testing each endpoint to assure an overall error rate of p ≤ 0.05. 
The details of the testing procedures will be provided in the statistical analysis plan for the study. 
Supportive Endpoints: 
The supportive variables will evaluate assessments at various study time points and using various 
populations.  
 
Proportion of 2-level PR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 2 levels of severity in the PR-PCSS) of the left buttock 
(Days 22, 43, and 71) 
 
Proportion of 2-level PR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 2 levels of severity in the PR-PCSS) of the right buttock 
(Days 22, 43, and 71) 
 
Proportion of 1-level PR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 1 level of severity in the PR-PCSS) of the left buttock 
(Days 22, 43, and 71) 
 
Proportion of 1-level PR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 1 level of severity in the PR-PCSS) of the right buttock 
(Days 22, 43, and 71) 
 
Proportion of 2-level PR-PCSS responders of at least one buttock (Days 22, 43, and 71). A 
subject will be considered a responder if this criterion is met in the left buttock or right 
buttock or both buttocks in that subject. 
 
Proportion of 1-level PR-PCSS responders of at least one buttock (Days 22, 43, and 71). A 
subject will be considered a responder if this criterion is met in the left buttock or right 
buttock or both buttocks in that subject.  
 
Proportion of 2-level PR-PCSS responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both left and 
right buttocks. 
 
Proportion of 1-level PR-PCSS responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both left and 
right buttocks. 
 
Proportion of 2-level CR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 2 levels of severity in the CR-PCSS) of the left buttock 
(Days 22, 43, and 71)  
 
Proportion of 2-level CR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 2 levels of severity in the CR-PCSS) of the right buttock 
(Days 22, 43, and 71) 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
 
Proportion of 1-level CR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 1 level of severity in the CR-PCSS) of the left buttock 
(Days 22, 43, and 71) 
 
Proportion of 1-level CR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 1 level of severity in the CR-PCSS) of the right buttock 
(Days 22, 43, and 71) 
 
Proportion of 2-level CR-PCSS responders of at least one buttock (Days 22, 43, and 71). A 
subject will be considered a responder if this criterion is met in the left buttock or right 
buttock or both buttocks in that subject 
 
Proportion of 1-level CR-PCSS responders of at least one buttock (Days 22, 43, and 71). A 
subject will be considered a responder if this criterion is met in the left buttock or right 
buttock or both buttocks in that subject 
 
Proportion of 2-level CR-PCSS responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both left and 
right buttocks 
 
Proportion of 1-level CR-PCSS responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both left and 
right buttocks 
 
Proportion of 1-level composite responders of the left buttock (defined as subjects with an 
improvement in severity from baseline of at least 1 level of severity in the CR-PCSS of the 
left buttock assessed live by the Investigator and an improvement of severity from baseline 
of at least 1 level of severity in the PR-PCSS of that same left buttock) (Days 22, 43, 
and 71) 
 
Proportion of 1-level composite responders of the right buttock (defined as subjects with an 
improvement in severity from baseline of at least 1 level of severity in the CR-PCSS of the 
right buttock assessed live by the Investigator and an improvement of severity from baseline 
of at least 1 level of severity in the PR-PCSS of that same right buttock) (Days 22, 43, 
and 71) 
 
Proportion of 1-level composite responders of at least one buttock (Days 22, 43, and 71). A 
subject will be considered a responder if this criterion is met in the left buttock or right 
buttock or both buttocks in that subject. 
 
Proportion of 1-level composite responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both left and 
right buttocks. 
 
Proportion of 2-level composite responders of the left buttock (defined as subjects with an 
improvement in severity from baseline of at least 2 levels of severity in the CR-PCSS of the 
left buttock assessed live by the Investigator and an improvement of severity from baseline 
of at least 2 levels of severity in the PR-PCSS of that same left buttock) (Days 22, 43, 
and 71) 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
 
Proportion of 2-level composite responders of the right buttock (defined as subjects with an 
improvement in severity from baseline of at least 2 levels of severity in the CR-PCSS of the 
right buttock assessed live by the Investigator and an improvement of severity from baseline 
of at least 2 levels of severity in the PR-PCSS of that same right buttock) (Days 22, 43, 
and 71) 
 
Proportion of 2-level composite responders of at least one of two buttocks (Days 22, 43, 
and 71). A subject will be considered a responder if this criterion is met in the left buttock 
or right buttock or both buttocks in that subject.  
 
Proportion of 2-level composite responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both left and 
right buttocks. 
 
Proportion of subjects at each level of the S-GAIS of the left buttock (Days 22, 43, and 71) 
 
Proportion of subjects at each level of the S-GAIS of the right buttock (Days 22, 43, and 71) 
 
Proportion of 1-level S-GAIS responders defined as subjects with a response of at least 1 
(improved) in the S- GAIS of the left buttock (Days 22, 43, and 71) 
 
Proportion of 1-level S-GAIS responders defined as subjects with a response of at least 1 
(improved) in the S- GAIS of the right buttock (Days 22, 43, and 71) 
 
Proportion 1-level S-GAIS responders of at least one buttock (Days 22, 43, and 71). A 
subject will be considered a responder if this criterion is met in the left buttock or right 
buttock or both buttocks in that subject. 
 
Proportion of 1-level S-GAIS responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both left and 
right buttocks. 
 
Proportion of subjects at each level of the I-GAIS of the left buttock (Days 22, 43, and 71) 
 
Proportion of subjects at each level of the I-GAIS of the right buttock (Days 22, 43, and 71) 
 
Proportion of 1-level I-GAIS responders (defined as subjects with a response of at least 1 
(improved) in the Investigator GAIS assessment) of at least one buttock (Days 22, 43, 
and 71). A subject will be considered a responder if this criterion is met in the left buttock 
or right buttock or both buttocks in that subject.  
 
Proportion of 1-level I-GAIS responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both left and 
right buttocks. 
 
Change from baseline (Day 1) of the PR-CIS total score at Day 71 
 
Change from baseline (Day 1) of the abbreviated PR-CIS score at Day 71 
 
Proportion of subjects with a change from baseline (Day1) of the PR-CIS ≥12 at Day 71 
 
Proportion of subjects with a change from baseline (Day 1) of the abbreviated PR-CIS ≥10 
at Day 71 
 
Proportion of subjects at each level of the subject satisfaction with cellulite treatment 
(Day 71) 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
 
Proportion of satisfied responders (defined as subjects with a response of at least 1 
(ie, 1-Satisfied or 2-Very Satisfied) in the subject satisfaction with cellulite treatment 
assessment (Day 71) 
All supportive endpoints will be summarized as percentages. The dichotomous secondary endpoints 
(ie, responder endpoints) will be analyzed using a Cochran-Mantel-Haenszel test adjusted for 
Investigator. Changes in the PR-PCSS ratings and CR-PCSS ratings from baselines, S-GAIS scores, and 
I-GAIS scores will be analyzed using the Mann-Whitney test. 
Safety Analysis: 
The following variables are safety endpoints: 
 
AEs: Mapped to preferred term using the Medical Dictionary for Regulatory Activities 
(MedDRA) 
 
Vital signs 
 
Clinical laboratory tests 
AEs will be summarized by proportion of subjects reporting each event. Fisher exact test will be used to 
compare EN3835 to placebo. Descriptive statistics will be presented for actual and change from baseline 
at each visit for vital signs and for each clinical laboratory test parameter. The comparison between 
treatment groups will be based on the change from baseline for clinical laboratory tests and vital signs 
using an analysis of variance (ANOVA) with a factor of drug (EN3835 or placebo). 
Immunogenicity: Anti-AUX-I and anti-AUX-II antibody levels will be summarized using descriptive 
statistics for the actual value at the visit. Samples from Day 1, Day 22, Day 43, and Day 71 visits will be 
analyzed for anti-AUX-I and anti-AUX-II antibodies and a subset of Day 1 and Day 71 samples will be 
analyzed for neutralizing antibodies. 

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5. 
SCHEDULE OF EVENTS 
Procedures 
Day -14 to -1 
Screening 
Day 1 
Treatment  
Visit 1 
Day 22 (± 3 d) 
Treatment  
Visit 2 
Day 43 (± 3 d) 
Treatment  
Visit 3 
Day 71 (+ 5 d) / 
End of Study / 
Early Termination 
Unscheduled 
Clinic Visita 
Informed consent 
X 
 
 
 
 
 
Inclusion/exclusion 
X 
 
 
 
 
 
Digital photography 
X 
Xb 
Xb 
Xb 
X 
X 
Medical history/EFP history including previous 
treatments 
X 
 
 
 
 
 
Prior/concomitant medications/procedures 
X 
X 
X 
X 
X 
X 
Physical examination: 
X 
 
 
 
 
 
 Body weight 
X 
 
Xc 
Xc 
X 
X 
 Height  
X 
 
 
 
 
 
 Fitzpatrick skin type 
X 
 
 
 
 
 
Vital signs 
X 
Xd 
Xd 
Xd 
X 
X 
12-lead ECG 
X 
 
 
 
 
 
Collection of samples: 
 Clinical laboratory 
X 
 
 
 
X 
X 
 Anti-AUX-I/anti-AUX-II antibody level 
 
Xc 
Xc 
Xc 
X 
 
 Pregnancy testing 
Xe 
Xc,e 
Xc,e 
Xc,e 
Xe 
X 
Subject cellulite assessmentsf: 
 Patient Reported Photonumeric Cellulite 
Severity Scale (PR-PCSS) 
Xg,h 
Xc,g,h 
Xc,g,h 
Xc,g,h 
Xg,h 
 
 Subject Global Aesthetic Improvement 
(S-GAIS) 
 
 
Xc,g,h 
Xc,g,h 
Xg,h 
 
 Patient Reported Cellulite Impact Scale 
(PR-CIS) 
 
Xc,g 
 
 
Xg 
 
 Subject Satisfaction With Cellulite Treatment 
Assessment 
 
 
 
 
Xg 
 
Investigator cellulite assessments: 
 Selection of dimples to be treated within the 
two buttocks 
 
Xc 
Xc 
Xc 
 
 
 Marking the dimples and injection sites to be 
treated within the buttocks 
 
Xc 
Xc 
Xc 
 
 
 Clinician Reported Photonumeric Cellulite 
Severity Scale (CR-PCSS) 
X 
Xc,h 
Xc,h 
Xc,h 
Xh 
 
 Investigator Global Aesthetic Improvement 
(I-GAIS)  
 
 
Xc,h 
Xc,h 
Xc,h 
 
 
 

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Procedures 
Day -14 to -1 
Screening 
Day 1 
Treatment  
Visit 1 
Day 22 (± 3 d) 
Treatment  
Visit 2 
Day 43 (± 3 d) 
Treatment  
Visit 3 
Day 71 (+ 5 d) / 
End of Study / 
Early Termination 
Unscheduled 
Clinic Visita 
Confirm eligibility 
 
Xc 
 
 
 
 
Randomize to treatment 
 
Xc,i 
 
 
 
 
Study drug administration 
 
X 
X 
X 
 
 
Injection site reactions/local tolerability in the 
buttocks 
 
X 
X 
X 
X 
X 
Adverse events 
Monitored Throughout Study 
a During unscheduled visits, the Investigator or designee may perform any study procedure that they deem clinically necessary (eg, vital signs, clinical lab assessments, and 
pregnancy test). 
b Before and after marking the dimples and injection sites. 
c Before injection. 
d Up to 4 hours before injection; approximately 15 and 30 minutes after injection. Vital signs must be stable before the subject is discharged. 
e Serum pregnancy test on Screening visit and Day 71/EOS visit; urine pregnancy test on Day 1, Day 22, and Day 43 visits. 
f Subject assessments should be completed independently and prior to Investigator assessments at each visit. 
g Assessment made via photographs (if treatment visit, use photographs taken before marking dimples and injection sites). 
h Assessment of each of the 2 buttocks independently. 
i Before randomization, each of the subject’s buttocks must have ratings of 3 or 4 (moderate or severe) in both the CR-PCSS and PR-PCSS. 
NOTE: Subject cellulite assessments must be completed before the Investigator cellulite assessments are conducted at each visit.  
d=Days; ECG=Electrocardiogram; EFP=Edematous fibrosclerotic panniculopathy; EOS=End of study 

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6. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES 
TABLE OF CONTENTS 
1. 
TITLE PAGE ................................................................................................................1 
2. 
SUMMARY OF CHANGES ........................................................................................2 
3. 
SPONSOR CONTACT INFORMATION .................................................................11 
4. 
SYNOPSIS .................................................................................................................12 
5. 
SCHEDULE OF EVENTS .........................................................................................22 
6. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............24 
7. 
LIST OF ABBREVIATIONS .....................................................................................30 
8. 
INTRODUCTION ......................................................................................................31 
8.1. 
Background .................................................................................................................31 
8.1.1. 
Edematous Fibrosclerotic Panniculopathy .................................................................31 
8.1.2. 
Current EFP Treatments .............................................................................................31 
8.1.3. 
EN3835 (Collagenase Clostridium Histolyticum) ......................................................32 
8.2. 
Summary of Nonclinical Studies ................................................................................33 
8.3. 
Summary of Known Risks and Benefits .....................................................................33 
8.4. 
Rationale .....................................................................................................................34 
9. 
OBJECTIVES .............................................................................................................35 
9.1. 
Primary Objective .......................................................................................................35 
9.2. 
Secondary Objectives .................................................................................................35 
9.3. 
Exploratory Objectives ...............................................................................................35 
10. 
INVESTIGATIONAL PLAN .....................................................................................36 
10.1. 
Study Design ...............................................................................................................36 
10.2. 
Selection of Doses ......................................................................................................36 
10.3. 
Study Drug Administration .........................................................................................37 
10.4. 
Care Procedures After Injection .................................................................................39 
10.5. 
Discussion of Study Design, Including the Choice of Control Groups ......................39 
11. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................40 
11.1. 
Subject Inclusion Criteria ...........................................................................................40 
11.2. 
Subject Exclusion Criteria ..........................................................................................40 
11.3. 
Subject Discontinuation Criteria .................................................................................42 

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11.3.1. 
Replacement Procedures .............................................................................................42 
12. 
TREATMENT OF SUBJECTS ..................................................................................43 
12.1. 
Study Visits .................................................................................................................43 
12.1.1. 
Informed Consent .......................................................................................................43 
12.1.2. 
Subject Screening .......................................................................................................43 
12.1.2.1. 
Medical History ..........................................................................................................43 
12.1.2.2. 
Screening Period (Day -14 to Day -1) ........................................................................43 
12.2. 
Selecting and Marking Dimples during Treatment Visits ..........................................44 
12.3. 
Digital Photography during Treatment Visits 1, 2, and 3 ...........................................45 
12.4. 
Treatment Visit 1 (Day 1) ...........................................................................................46 
12.4.1. 
Treatment Visit 1: Pre-Injection .................................................................................46 
12.4.2. 
Treatment Visit 1: Injection and Post-injection ..........................................................46 
12.5. 
Treatment Visit 2 (Day 22 [±3 days]) and Treatment Visit 3 (Day 43 [±3 
days]) ..........................................................................................................................47 
12.5.1. 
Treatment Visits 2 and 3: Pre-injection ......................................................................47 
12.5.2. 
Treatment Visits 2 and 3: Injection and Post-injection ..............................................47 
12.6. 
Day 71 (+5 days) End of Study / Early Termination ..................................................48 
12.7. 
Unscheduled Visits .....................................................................................................48 
12.8. 
Prior and Concomitant Medications and Procedures ..................................................48 
12.8.1. 
Prohibited Medications or Procedures ........................................................................49 
12.9. 
Treatment Compliance ................................................................................................49 
12.10. 
Blinding and Randomization ......................................................................................49 
13. 
ASSESSMENT OF EFFICACY ................................................................................51 
13.1. 
Efficacy Measurements ..............................................................................................51 
13.1.1. 
Digital Photography ....................................................................................................51 
13.1.2. 
Subject and Investigator Cellulite Assessments .........................................................51 
13.1.2.1. 
Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) ........................51 
13.1.2.2. 
Subject Global Aesthetic Improvement Scale (S-GAIS) ............................................52 
13.1.2.3. 
Patient Reported Cellulite Impact Scale (PR-CIS) .....................................................53 
13.1.2.4. 
Subject Satisfaction with Cellulite Treatment Assessment ........................................53 
13.1.2.5. 
Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) ....................54 
13.1.2.6. 
Investigator Global Aesthetic Improvement Scale (I-GAIS) .....................................54 
14. 
ASSESSMENT OF SAFETY .....................................................................................55 

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14.1. 
Definitions ..................................................................................................................55 
14.1.1. 
Adverse Events ...........................................................................................................55 
14.1.2. 
Serious Adverse Events ..............................................................................................55 
14.2. 
Monitoring Adverse Events ........................................................................................56 
14.3. 
Relationship to Study Drug ........................................................................................56 
14.4. 
Intensity Assessment ..................................................................................................57 
14.5. 
Reporting Adverse Events and Serious Adverse Events ............................................57 
14.5.1. 
Reporting Adverse Events ..........................................................................................57 
14.5.2. 
Reporting Serious Adverse Events .............................................................................57 
14.5.2.1. 
Follow-up Procedures for Serious Adverse Events ....................................................58 
14.6. 
Special Reporting Situations .......................................................................................58 
14.6.1. 
Adverse Events of Special Interest .............................................................................58 
14.6.2. 
Overdose/Misuse/Abuse .............................................................................................58 
14.6.2.1. 
Overdose .....................................................................................................................58 
14.6.3. 
Pregnancy ...................................................................................................................59 
14.6.4. 
AEs/SAEs Experienced by Non-subjects Exposed to Study Medication ...................59 
14.7. 
Clinical Laboratory Determinations ...........................................................................59 
14.8. 
Anti-AUX-I and Anti-AUX-II Antibodies .................................................................61 
14.9. 
Vital Signs ..................................................................................................................61 
14.10. 
Electrocardiogram .......................................................................................................61 
14.11. 
Physical Examination .................................................................................................62 
14.12. 
Other Safety Assessments ...........................................................................................62 
15. 
ASSESSMENT OF PHARMACOKINETICS ...........................................................63 
16. 
ASSESSMENT OF PHARMACODYNAMICS ........................................................64 
17. 
STATISTICAL CONSIDERATIONS AND METHODS .........................................65 
17.1. 
Determination of Sample Size ....................................................................................65 
17.2. 
Subject Populations ....................................................................................................65 
17.2.1. 
Safety Population ........................................................................................................65 
17.2.2. 
Intent-to-Treat (ITT) Population .................................................................................66 
17.2.3. 
Modified Intent-to-Treat (mITT) Population ..............................................................66 
17.2.4. 
Per-Protocol (PP) Population ......................................................................................66 
17.3. 
Subject Disposition .....................................................................................................66 
17.4. 
Demographics and Other Baseline Characteristics .....................................................66 

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17.5. 
Efficacy Analyses .......................................................................................................67 
17.5.1. 
Primary Efficacy Variable ..........................................................................................67 
17.5.2. 
Secondary Efficacy Variables .....................................................................................68 
17.5.2.1. 
Key Secondary Variables ...........................................................................................68 
17.5.3. 
Supportive Efficacy Variables ....................................................................................69 
17.5.3.1. 
Supportive Variables ..................................................................................................69 
17.6. 
Safety Analyses ..........................................................................................................72 
17.6.1. 
Prior, Concomitant, and Follow-up Medication .........................................................72 
17.6.2. 
Study Drug Exposure ..................................................................................................72 
17.6.3. 
Measurement of Treatment Compliance ....................................................................72 
17.6.4. 
Adverse Events ...........................................................................................................72 
17.6.5. 
Vital Signs ..................................................................................................................73 
17.6.6. 
Clinical Laboratory Parameters ..................................................................................73 
17.6.7. 
Electrocardiogram .......................................................................................................74 
17.6.8. 
Physical Examination .................................................................................................74 
17.6.9. 
Other Safety Measurements ........................................................................................74 
17.7. 
Pharmacokinetic Analyses ..........................................................................................74 
17.8. 
Pharmacodynamic Analyses .......................................................................................74 
17.9. 
Other Data (eg, Health Economics/QOL, Pharmacogenetic, etc) ..............................74 
17.10. 
Interim Analysis ..........................................................................................................74 
17.11. 
Statistical Software .....................................................................................................74 
18. 
STUDY DRUG MATERIALS AND MANAGEMENT ...........................................75 
18.1. 
Study Drug Identity ....................................................................................................75 
18.2. 
Study Drug Packaging and Labeling ..........................................................................75 
18.3. 
Study Drug Storage .....................................................................................................75 
18.4. 
Study Drug Preparation ..............................................................................................75 
18.5. 
Study Drug Accountability .........................................................................................76 
18.5.1. 
Study Drug Handling and Disposal ............................................................................76 
19. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS .........................................77 
19.1. 
Source Documents ......................................................................................................77 
19.2. 
Study Monitoring ........................................................................................................77 
19.3. 
Audits and Inspections ................................................................................................77 
19.4. 
Institutional Review Board (IRB) ...............................................................................77 

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19.5. 
Data Recording and Documentation ...........................................................................78 
20. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................79 
21. 
ETHICS ......................................................................................................................80 
21.1. 
Ethics Review .............................................................................................................80 
21.2. 
Ethical Conduct of the Study ......................................................................................80 
21.3. 
Subject Information and Consent ...............................................................................81 
22. 
DATA HANDLING AND RECORDKEEPING .......................................................82 
22.1. 
Data Collection ...........................................................................................................82 
22.2. 
Study Documentation .................................................................................................82 
23. 
REPORTING AND PUBLICATION .........................................................................83 
24. 
INVESTIGATOR OBLIGATIONS ...........................................................................84 
24.1. 
Regulatory Documents ...............................................................................................84 
24.2. 
Delegation of Responsibilities and Adequate Resources ...........................................85 
24.3. 
Medical Care of Study Subjects .................................................................................85 
24.4. 
Use of Investigational Materials .................................................................................85 
24.5. 
Retention of Records ..................................................................................................85 
24.6. 
Subject Confidentiality ...............................................................................................86 
25. 
TERMINATION OF STUDY ....................................................................................87 
26. 
INVESTIGATOR’S STATEMENT ...........................................................................88 
27. 
REFERENCES ...........................................................................................................89 
APPENDIX A. DOCUMENTS REQUIRED PRIOR TO INITIATION OF THE 
STUDY .......................................................................................................................90 
APPENDIX B. PATIENT-REPORTED PHOTONUMERIC CELLULITE SEVERITY 
SCALE (PR-PCSS) FOR THE BUTTOCK ...............................................................92 
APPENDIX C. CLINICIAN-REPORTED PHOTONUMERIC CELLULITE 
SEVERITY SCALE (CR-PCSS) FOR THE BUTTOCK ..........................................93 
APPENDIX D. PATIENT REPORTED CELLULITE IMPACT SCALE (PR-CIS) ................94 
 

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LIST OF TABLES 
Table 1: 
Sponsor Contact Information ......................................................................................11 
Table 2: 
Abbreviations and Special Terms ...............................................................................30 
Table 3:  
Study Treatment Groups .............................................................................................36 
Table 4: 
Concomitant Medication Restrictions for Subjects during the Treatment 
Phase of Study ............................................................................................................49 
Table 5: 
Subject Global Aesthetic Improvement Scale (S-GAIS) ............................................53 
Table 6: 
Subject Satisfaction with Cellulite Treatment Assessment - Buttocks .......................53 
Table 7: 
Investigator Global Aesthetic Improvement Scale (I-GAIS) .....................................54 
Table 8: 
Clinical Laboratory Tests ...........................................................................................60 
Table 9: 
Vital Signs Measurements on Injection Day ..............................................................61 
Table 10: Fitzpatrick Scale .........................................................................................................62 
 
LIST OF FIGURES 
Figure 1: 
Study Design ...............................................................................................................36 
Figure 2: 
Study Drug Administration at Each Injection Site .....................................................38 
 
 

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7. 
LIST OF ABBREVIATIONS  
The following abbreviations and specialized terms are used in this study protocol. 
Table 2: 
Abbreviations and Special Terms 
Abbreviation 
Definition 
AE 
Adverse event 
AUX-I 
Clostridial class I collagenase 
AUX-II 
Clostridial class II collagenase 
BMI 
Body mass index 
CR-PCSS 
Clinician Reported Photonumeric Cellulite Severity Scale 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
EFP 
Edematous fibrosclerotic panniculopathy 
ePRO 
Electronic patient reported outcome 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HREC 
Human Research Ethics Committee 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
I-GAIS 
Investigator-Global Aesthetic Improvement Scale 
IRB 
Institutional Review Board 
ITT 
Intent-to-treat 
IWRS 
Interactive web response system 
LOCF 
Last observation carried forward 
mITT 
Modified intent-to-treat 
PR-CIS 
Patient Reported Cellulite Impact Scale 
PR-PCSS 
Patient Reported Photonumeric Cellulite Severity Scale 
Quadrant 
A quadrant is a treatment area 
Qualified designee 
Qualified by education and training to perform the study procedure (eg, 
sub-Investigator, nurse). 
SAE 
Serious adverse event 
S-GAIS 
Subject – Global Aesthetic Improvement Scale 
TEAE 
Treatment-emergent adverse event. Adverse events that occur on or after the 
first injection of study drug. 

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8. 
INTRODUCTION 
8.1. 
Background 
8.1.1. 
Edematous Fibrosclerotic Panniculopathy 
Edematous fibrosclerotic panniculopathy (EFP), commonly known as cellulite, has been defined 
as a local metabolic disorder of subcutaneous tissues that results in a contour abnormality of the 
skin.(1) The condition manifests as dimpled skin, particularly in the gluteal-femoral region.(2,3) 
EFP is caused by herniation of subcutaneous fat lobules through the dermohypodermal junction 
and/or shortening of the collagen septa that cross the hypodermal layer and connects the dermis 
to the underlying fascia. This creates an uneven surface with dimpling.(1,2) EFP is a medical 
condition resulting in a potentially cosmetically unacceptable alteration of the skin, and affects 
an estimated 85% to 98% of postpubertal women.(1,3) 
The pathophysiology of EFP is not completely understood, but there are 3 main theories: edema 
resulting from excessive hydrophilia of the intercellular matrix, alteration of the regional 
microcirculation, and different anatomical conformation of collagenous subcutaneous tissues in 
women versus men.(4) 
It is known that EFP is different from generalized obesity. In generalized obesity, adipocytes 
undergo hypertrophy and hyperplasia that are not limited to the pelvis, thighs, and abdomen.(1) 
In areas of EFP, adipocytes have physiologic and biochemical properties that differ from adipose 
tissue located elsewhere. Large, metabolically-stable adipocytes characterize EFP-prone areas; 
thus, the responsiveness to catecholamine-induced lipolysis is less in EFP tissues compared to 
visceral fat, which has the greatest responsiveness.(1) 
Subcutaneous fat lobes are separated from one another by thin, usually rigid strands of 
collagenous connective tissues, which cross the fatty layers and connect the dermis to the 
underlying fascia. These septa stabilize the subcutis and divide the fat. In EFP, shortening of the 
collagen septa due to fibrosis provokes retraction at the insertion points of the trabeculae, 
causing the depressions that characterize EFP.(2) There are a higher percentage of thinner, 
perpendicular hypodermal septa in women with EFP than in men.(1) Weight gain makes EFP 
more noticeable, but it may be present even in thin subjects. Genetics may also play a role since 
EFP tends to run in families. 
8.1.2. 
Current EFP Treatments 
There are therapies that have been utilized in an attempt to treat cellulite; however, there are no 
approved pharmacologic treatments. Despite multiple therapeutic modalities, there is little 
scientific evidence that any of these treatments are beneficial. In fact, much of the evidence is 
anecdotal, subjective, or based only on patient self-assessment.(5) Some of the historical 
treatments for EFP have included weight loss,(6) topical agents,(5) massage,(7) liposuction,(5,6) 
mesotherapy,(6) radiofrequency,(6) subcision and powered subcision,(8) and laser 
therapies;(9,10) some of these treatments may pose an increased risk for adverse effects.(5) 

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There remains an unmet medical need for safe and effective therapies to improve the aesthetic 
outcome in women with cellulite. To effectively treat cellulite, a therapeutic approach may 
require disruption of the dermal septa, which are composed of collagen and cause the skin 
dimpling that is bothersome to many women. 
8.1.3. 
EN3835 (Collagenase Clostridium Histolyticum) 
Endo Pharmaceuticals Inc. (Endo) is developing EN3835 for the treatment of EFP. Because 
EN3835 is a proteinase that can hydrolyze the triple-helical region of collagen under 
physiological conditions, EN3835 has the potential to be effective in lysing subdermal collagen, 
such as those observed in the dermal septa, which are the underlying cause of the skin dimpling 
in women with EFP. EN3835 targets the collagenase structural matrix (eg, dermal septa) at the 
site of injection and does not require systemic exposure to be effective. 
EN3835 is a parenteral lyophilized product comprised of 2 collagenases in an approximate 1:1 
mass ratio, Collagenase I (AUX-I, Clostridial class I collagenase) and Collagenase II (AUX-II; 
Clostridial class II collagenase). These collagenases are isolated and purified from the 
fermentation of Clostridium histolyticum. 
Collagenase AUX-I is a single polypeptide chain containing approximately 1,000 amino acids of 
known sequence and with a molecular weight of 114 kDa. Collagenase AUX-II is also 
approximately 1,000 amino acids long and has a molecular weight of 113 kDa. These 
2 collagenases are not immunologically cross-reactive and have different specificities, such that 
together they become synergistic, providing a very broad hydrolyzing reactivity toward collagen. 
Clostridial collagenases are proteinases that can hydrolyze the triple-helical region of collagen 
under physiological conditions. 
EN3835 is currently approved (brand name is XIAFLEX®) for: 1) the treatment of adults with 
Dupuytren’s contracture with a palpable cord and, 2) for the treatment of adult men with 
Peyronie’s disease with a palpable plaque and curvature deformity of at least 30° at the start of 
therapy. 
A recent Phase 2b, randomized, double-blind, placebo-controlled study (EN3835-201) of 
375 women randomized to treatment of one treatment area (quadrant) (quadrant was defined in 
study EN3835-201 as a left buttock, a right buttock, a left posterolateral thigh or a right 
posterolateral thigh) of cellulite with EN3835 0.84 mg or placebo in a 1:1 ratio assessed the 
effectiveness and safety of EN3835. Efficacy in this study was evaluated based on cellulite 
assessments using Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS), Patient 
Reported Photonumeric Cellulite Severity Scale (PR-PCSS), Investigator Global Aesthetic 
Improvement Scale (GAIS-I), Subject Global Aesthetic Improvement Scale (GAIS-S), and 
Subject Satisfaction with Cellulite Treatment. 
Results from the Phase 2b study demonstrated that treatment (3 visits approximately 21 days 
apart) improved the cellulite severity of the treatment area as assessed by the primary endpoint of 
2-level composite responder analyses, the proportion of responders based on an improvement of 
≥2 levels in the appearance of cellulite in both the patient PR-PCSS and the clinician CR-PCSS 
of buttocks and thighs was statistically significantly greater in subjects who received EN3835 
0.84 mg (10.6%; p<0.001) compared to subjects who received placebo (1.6%); 1-level (or 
greater) responders in the PR-PCSS of EN3835-treated subjects (72.3%) was significantly 

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greater than 1-level responders in the placebo group (51.6%) (p<0.001); statistically significant 
(p≤0.001) improvement in the appearance of cellulite based on the subject S-GAIS were 
observed in EN3835 0.84-mg group (73.1%) compared to the placebo group (44.0%); and 62.9% 
of subjects in the EN3835 0.84 mg group were satisfied or very satisfied with the results of their 
cellulite treatment compared with only 35.9% of subjects in the placebo group (p<0.001). In 
subjects treated in buttocks (n=187), the proportion of 2-level composite responders was 
statistically significantly greater in subjects who received EN3835 0.84 mg (14.9%; p<0.001) 
compared to subjects who received placebo (1.1%); 1-level (or greater) responders in the 
PR-PCSS of EN3835-treated subjects (72.7%) was significantly greater than 1-level responders 
in the placebo group (47.8%) (p<0.001). 
The study also demonstrated EN3835 to be well tolerated with no serious adverse events (SAEs) 
related to EN3835. Safety results from a total of 4 studies (1 pilot, 2 Phase 1, and 2 Phase 2 
studies) in which 435 adult females received subcutaneous injections of EN3835 indicate that the 
majority of treatment-emergent adverse events (TEAEs) are transient, non-serious, mild or 
moderate in intensity, and related to the local administration of EN3835. The immunogenicity 
profile after 3 treatment visits of EN3835 indicate that greater than 90% of EN3835-treated 
subjects were seropositive for AUX-I and/or AUX-II antibodies; this profile of EN3835 is 
similar to that observed in the Dupuytren’s contracture and Peyronie’s disease programs. 
A Phase 1, open-label safety and pharmacokinetic study of a single dose of EN3835 0.84 mg in 
11 female subjects with EFP showed that there was no quantifiable levels of AUX-I or AUX-II 
at any time point after subcutaneous injection of EN3835 0.84 mg into one quadrant. A second 
Phase 1, open-label safety and pharmacokinetic study of a single dose of EN3835 0.84 mg per 
treatment area in two treatment areas (buttock-buttock, thigh-thigh, or buttock-thigh) 
concurrently (total dose of 1.68 mg) showed that there was no quantifiable levels of AUX-I or 
AUX-II at any time point post-dose attributable to the injection of EN3835 1.68 mg. 
The results from these studies suggest that subcutaneous injections of EN3835 in the area of 
cellulite may be a well-tolerated and effective medical treatment for adults with EFP. 
8.2. 
Summary of Nonclinical Studies 
Non-clinical studies necessary to support clinical studies have been performed and are 
summarized in the Investigator Brochure (IB).(11) Non-clinical studies in the following areas 
were performed: toxicology, reprotoxicity, genotoxicity, and hypersensitivity. 
8.3. 
Summary of Known Risks and Benefits 
A summary of safety risks is provided in the IB.(11) The following events have been commonly 
observed: local injection site reactions (injection site bruising, injection site swelling, injection 
site pain) for the various approved indications as well as those being investigated. In the phase 
2b study of EN3835 in women with EFP, the following treatment related adverse events ≥2% of 
189 EN3835-treated women were reported: injection site bruising (75.1%), injection site pain 
(59.3%), injection site nodule (14.3%), injection site pruritus (11.1%), injection site swelling 
(7.4%), injection site induration (5.8%), injection site mass (5.3%), injection site discolouration 
(3.2%), and injection site erythema (2.1%). These events are similar to events reported in the 
clinical trials of EN3835 for the approved indications. Postmarketing safety data are consistent 
with safety data reported in clinical trials. 

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Although a thorough benefit of EN3835 has not been fully evaluated in the treatment of EFP, the 
efficacy results from the Phase 2b study and previous EFP studies warranted further 
development. 
8.4. 
Rationale 
The results from the Phase 2b EFP study (EN3835-201) further suggested that EN3835 0.84 mg 
per treatment area (quadrant) is an effective treatment of EFP based on improvement in the 
severity of cellulite as determined by the Investigator and the subject. There were no safety 
concerns following 0.84 mg per treatment area in the treatment of EFP (section 8.1.3). Safety 
findings from the Phase 2b EFP study are similar to that observed in previous clinical studies 
with EN3835 in the treatment of EFP and XIAFLEX in the treatment of Dupuytren’s contracture 
and Peyronie’s disease, in that that the majority of AEs occurred at the site of injection and 
resolved before the next scheduled treatment. The immunogenicity profile of EN3835 in the 
Phase 2b EFP study is similar in previous studies and programs. 
Based on the efficacy and safety findings from the Phase 2a and 2b EFP studies, the EN3835 
0.84-mg dose per treatment area in two treatment areas (buttocks) warranted further investigation 
in this study. 
Treating two buttocks at each treatment visit will potentially provide a symmetrical-like 
improvement in appearance. Support for evaluation of the treatment of two buttocks concurrently 
is based on: 1) the safety findings from the previous EFP studies are local to the injection site, 
2) the pharmacological activity of EN3835 is local and does not require systemic exposure, and 
3) no significant quantifiable systemic concentration has been attributable to injection of two 
buttocks concurrently. 
The integration of dose and use justification supports this study of evaluation of EN3835 
0.84 mg per treatment area in two treatment areas (buttocks) concurrently. 

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9. 
OBJECTIVES 
9.1. 
Primary Objective 
The primary objective of this study is to assess the efficacy and safety of EN3835 in the 
treatment of edematous fibrosclerotic panniculopathy (EFP) commonly known as cellulite in 
adult women. 
9.2. 
Secondary Objectives 
There are no secondary objectives of this study. 
9.3. 
Exploratory Objectives 
There are no exploratory objectives of this study. 

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10. 
INVESTIGATIONAL PLAN 
10.1. 
Study Design 
This study will be performed at approximately 25 study centers located in the United States. This 
clinical study will be conducted as a multicenter, randomized, double-blind, placebo-controlled 
study comparing EN3835 to placebo in adult women with EFP. The study will consist of 71 days 
of double-blind treatment. Subjects meeting the entry criteria for this study will be randomized to 
EN3835 treatment or placebo treatment in a 1:1 ratio within an investigational site.  
The complete Schedule of Events is provided in section 5. 
Figure 1: 
Study Design 
 
Table 3:  
Study Treatment Groups 
Dose per 
Each Injectiona / 
Number of 
Subjects 
Injection 
Volume per 
Each Injection 
Number of 
Injections at Each 
Treatment Visit 
Dose (mg) at Each 
Treatment Visit 
Injection Volume 
(mL) per Each 
Treatment Visit 
Cumulative EFP 
Dose 
EN3835 0.07 mg / 
N=210 
0.3 mL 
12 per buttock  
× 2 buttocks =  
24 injections 
0.84 mg per buttock  
× 2 buttocks = 
1.68 mg 
(12 injections  
per buttock ×  
0.07 mg/injection ×  
2 buttocks) 
3.6 mL per buttock  
× 2 buttocks = 
7.2 mL  
(24 injections × 
0.3 mL) 
5.04 mg 
(3 treatment visits × 
0.84 mg per buttock 
× 2 buttocks) 
Placebo /  
N=210 
0.3 mL 
12 per buttock  
× 2 buttocks =  
24 injections 
- 
3.6 mL per buttock  
× 2 buttocks = 
7.2 mL  
(24 injections × 
0.3 mL) 
- 
a Each injection of study drug is 0.3 mL administered as three 0.1 mL aliquots. 
10.2. 
Selection of Doses 
The dose of EN3835 chosen for this study was based on the results from earlier studies. 

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The data from the Phase 2a EFP dose-ranging study (AUX-CC-831) suggest that EN3835 
0.84 mg is most effective in the treatment of EFP based on improvement in the severity of 
cellulite as determined by both the Investigator and the subject, although the EN3835 0.48-mg 
group did show improvement in some of the efficacy parameters. 
 There were no safety concerns following administration of up to 3 treatment visits of 
EN3835 0.84 mg in the treatment of EFP (AUX-CC-831 CSR). The safety profile of 
EN3835 0.84 mg in the treatment of EFP was similar to that observed in the EN3835 
0.06-mg group and the EN3835 0.48-mg group. No notable differences were 
observed across the 3 treatment groups. 
 Safety findings from the Phase 2a EFP dose-ranging study are similar to that 
observed in previous clinical studies with XIAFLEX in the treatment of Dupuytren’s 
contracture and Peyronie’s disease, in that the majority of AEs occurred at the site of 
injection and resolved before the next scheduled treatment. 
 The immunogenicity profile of EN3835 in the Phase 2a EFP dose-ranging study is 
similar to that observed in the Dupuytren’s contracture and Peyronie’s disease 
programs. 
 Based on the efficacy and safety findings from the Phase 2a EFP dose-ranging study, 
the EN3835 0.84-mg dose was carried forward to the Phase 2b study. 
The results from the Phase 2b EFP study (EN3835-201) further suggested that EN3835 0.84 mg 
is an effective treatment of EFP based on improvement in the severity of cellulite as determined 
by the Investigator and the subject. There were no safety concerns following EN3835 0.84 mg 
in the treatment of EFP (section 8.4). Safety findings from the Phase 2b EFP study are similar to 
that observed in previous clinical studies with XIAFLEX in the treatment of Dupuytren’s 
contracture and Peyronie’s disease, in that that the majority of AEs occurred at the site of 
injection and resolved before the next scheduled treatment. The immunogenicity profile of 
EN3835 in the Phase 2b EFP study is similar to that observed in the Dupuytren’s contracture 
and Peyronie’s disease programs. 
Based on the efficacy and safety findings from the Phase 2a and 2b EFP studies, the EN3835 
0.84-mg dose per treatment area was carried forward to this study. The findings from previous 
studies that the majority of adverse events after EN3835 treatment are local to the injection site 
and that there is no quantifiable systemic exposure observed after concurrent treatment of two 
buttocks (total dose of 1.68 mg) supports the proposed study to evaluate EN3835 treatment of 
two buttocks. 
10.3. 
Study Drug Administration 
Study drug will be injected subcutaneously while the subject is in a prone position using a 
syringe with a 30-gauge ½-inch needle. Each injection site will receive a single skin injection of 
study drug administered as three 0.1-mL aliquots to Positions A, B, and C (for a total injection 
volume of 0.3 mL) as shown in the following figure. The depth of injection corresponds to the 
length of the treatment needle (0.5 inches) from the tip of the needle to the hub or base of the 
needle without downward pressure. 

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NOTE: EN3835 is a foreign protein and Investigators should be prepared to address and manage 
an allergic reaction should it occur. At the time of each injection, a 1:1,000 solution of 
epinephrine for injection, 50-mg diphenhydramine injection or a suitable equivalent, and oxygen 
must be available with the Investigator and site staff must be familiar with their use. 
10.4. 
Care Procedures After Injection 
To evaluate the subject for possible immediate immunological AEs, the subject will remain in 
direct observation of medical personnel who are skilled in the management of an allergic 
reaction for 30 minutes after receiving the injections of study drug and until the subject exhibits 
no sign of an immunological or other clinically significant systemic or local AE. The subject’s 
vital signs should be stable before the subject can leave direct observation (see section 14.9). 
The Investigator or qualified designee will then apply a sterile dressing to the injection areas 
with hypoallergenic tape. The subject will be instructed to remove the dressing in the evening. 
10.5. 
Discussion of Study Design, Including the Choice of Control Groups 
The design of this study was based on the primary objective to evaluate the efficacy and safety of 
EN3835 0.84 mg per buttock in the concurrent treatment (total dose of 1.68 mg) of 2 bilateral 
buttocks with EFP in adult women compared with placebo treatment. The study design, a 
multi-center, double-blind, placebo-controlled study is in accordance with regulatory guidelines 
of adequate and well-controlled clinical studies (Food and Drug Administration [FDA] Guidance 
for Industry: Providing Clinical Evidence of Effectiveness for Human Drug and Biological 
Products, 1998.; ICH E8 and E10). 

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11. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
11.1. 
Subject Inclusion Criteria 
In order to be eligible to participate in the study, subjects must meet the following criteria: 
1. Voluntarily sign and date an informed consent agreement 
2. Be a female ≥18 years of age 
3. At Screening visit, have 2 bilateral buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as reported by the Investigator (CR-PCSS) 
4. At Day 1 visit, have 2 bilateral buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as reported by the Investigator (CR-PCSS) 
5. Be willing to apply sunscreen to the buttocks before each exposure to the sun while 
participating in the study (ie, Screening through end of study) 
6. Be judged to be in good health, based upon the results of a medical history, physical 
examination, and laboratory profile at Screening 
7. Have a negative serum pregnancy test at Screening and a negative urine pregnancy test 
before injection of study drug and be using a stable and effective contraception method 
(eg, abstinence, intrauterine device [IUD], hormonal [estrogen/progestin] contraceptives, 
or double barrier method) for at least 1 menstrual cycle prior to study enrollment and for 
the duration of the study; or be menopausal defined as 12 months of amenorrhea in the 
absence of other biological or physiological causes, as determined by the Investigator; or 
post-menopausal for at least 1 year; or be surgically sterile 
8. Be willing and able to cooperate with the requirements of the study 
9. Be able to read, complete and understand the patient-reported outcomes rating 
instruments in English 
11.2. 
Subject Exclusion Criteria 
Subjects who meet any of the following criteria will not be eligible to participate in the study: 
1. Has any of the following systemic conditions: 
a. Coagulation disorder 
b. Evidence or history of malignancy (other than excised basal-cell carcinoma) unless 
there has been no recurrence in at least 5 years 
c. History of keloidal scarring or abnormal wound healing 

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d. Concurrent diseases or conditions that might interfere with the conduct of the study, 
confound the interpretation of the study results, or endanger the subject’s well-being. 
Any questions about concurrent diseases should be discussed with the Medical 
Monitor 
e. Evidence of clinically significant abnormalities on physical examination, vital signs, 
electrocardiogram (ECG), or clinical laboratory values 
2. Has any of the following local conditions in the areas to be treated: 
a. History of lower extremity thrombosis or post-thrombosis syndrome 
b. Vascular disorder (eg, varicose veins, telangiectasia) in area to be treated 
c. Inflammation or active infection 
d. Severe skin laxity, flaccidity, and/or sagging  
e. Active cutaneous alteration including rash, eczema, psoriasis, or skin cancer 
f. Has a tattoo and/or a mole located within 2 cm of the site of injection 
3. Requires the following concomitant medications before or during participation in the 
trial: 
a. Anticoagulant or antiplatelet medication or has received anticoagulant or antiplatelet 
medication (except for ≤150 mg aspirin daily) within 7 days before injection of study 
drug 
4. Has used any of the following for the treatment of EFP on a buttock within the timelines 
identified below or intends to use any of the following at any time during the course of 
the study: 
a. Liposuction in a buttock during the 12-month period before injection of study drug 
b. Injections (eg, mesotherapy); radiofrequency device treatments; laser treatment; 
buttock implant treatment; cryolipolysis; or surgery (including subcision and/or 
powered subcision) within a buttock during the 12-month period before injection of 
study drug 
c. Any investigational treatment for EFP on a buttock during the 12-month period 
before the injection of study drug 
d. Endermologie or similar treatments within a buttock during the 6-month period 
before injection of study drug 
e. Massage therapy within a buttock during the 3-month period before injection of study 
drug 
f. Creams (eg, Celluvera™, TriLastin®) and/or home therapies to prevent or mitigate 
EFP within a buttock during the 2-week period before injection of study drug 
5. Is presently nursing or providing breast milk 
6. Intends to become pregnant during the study 
7. Intends to initiate an intensive sport or exercise program during the study 
8. Intends to initiate a weight reduction program during the study 
9. Intends to use tanning spray or tanning booths during the study 

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10. Has received an investigational drug or treatment within 30 days before injection of study 
drug 
11. Has a known systemic allergy to collagenase or any other excipient of study drug 
12. Has received any collagenase treatments at any time prior to treatment 
13. Was a subject in a previous cellulite clinical trial of CCH: AUX-CC-830, AUX-CC-831, 
EN3835-102, EN3835-104, EN3835-201, and/or EN3835-202 
14. Any other condition(s) that, in the Investigator’s opinion, might indicate the subject to be 
unsuitable for the study  
11.3. 
Subject Discontinuation Criteria 
A premature discontinuation will occur when a subject who signed informed consent ceases 
participation in the study, regardless of circumstances, prior to the completion of the protocol. 
Subjects can be prematurely discontinued from the study for one of the following reasons: 
 An adverse event 
 Lack of efficacy 
 A protocol violation (reason must be specified, for example: lack of compliance, use 
of a prohibited concomitant medication, failure to meet inclusion/exclusion criteria 
after study entry, etc.) 
 Withdrawal by subject (reason must be specified) 
 The subject was “lost to follow-up” 
 Other reasons (reason must be specified, for example: the subject moved, pregnancy, 
Investigator decision, Sponsor decision to terminate trial, etc.) 
If a subject discontinues from the study, all end-of-study procedures including safety and 
efficacy assessments should be conducted as detailed in the Schedule of Events (section 5). The 
date a subject discontinues and the reason for discontinuation will be recorded in the source 
documentation and electronic case report form (eCRF). If, however, a subject withdraws consent, 
no end-of-study procedures and assessments are required (but are encouraged to reduce missing 
information) except the collection of adverse event (AE) information. This information should be 
recorded in the source documentation and the eCRF. 
11.3.1. 
Replacement Procedures 
Subjects who discontinue from the study will not be replaced. 

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12. 
TREATMENT OF SUBJECTS 
12.1. 
Study Visits 
The Schedule of Events to be performed at each visit is shown in section 5. Provided below are 
further details where additional instruction about the assessments that will be performed is 
deemed to be needed. 
12.1.1. 
Informed Consent 
Signed and dated informed consent will be obtained from each subject before any study 
procedures are undertaken, or before any changes to the subject’s medication regimen are made. 
Details about how the informed consent will be obtained and documented are provided in 
section 21.3, Subject Information and Consent. 
12.1.2. 
Subject Screening 
Investigators will be expected to maintain a Screening log of all potential study subjects. This log 
will include limited information about the potential subject and the date and outcome of the 
screening process (eg, enrolled into the study, reason for ineligibility, or refused to participate). 
Investigators will provide information about the study to subjects who appear to meet the criteria 
for participation in the study. The screening log will be captured directly by the electronic data 
capture (EDC) system. 
12.1.2.1. Medical History 
During the screening period, the Investigator or qualified designee will obtain a medical history 
from each subject that includes relevant diagnoses and/or procedures/therapies with 
onset/resolutions dates. Medical histories should also include history of EFP (start date and 
family history), and history of tobacco and alcohol use (never, current, former). 
12.1.2.2. Screening Period (Day -14 to Day -1) 
Subjects meeting the relevant eligibility criteria listed in section 11 may be enrolled in the study 
after the nature and purpose of the protocol have been explained and written informed consent to 
participate has been voluntarily provided by the subject or their legally authorized representative. 
The subject identification number will consist of 8 digits. The first 4 digits represent the study 
site number followed by a 4-digit subject number. 
The following procedures will be performed and documented during the screening period: 
1. Obtain written informed consent (section 12.1.1) 
2. Evaluate eligibility based on inclusion/exclusion criteria (section 11.1 and section 11.2) 
3. Subject will have digital photographs taken of her two buttocks (section 13.1.1) 
4. Subjects will get instruction on the use of the PR-PCSS (section 13.1.2.1) 

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5. Prior to Investigator CR-PCSS assessment, subjects will rate each of their two buttocks 
using the PR-PCSS while viewing their digital images (section 13.1.2.1); the Investigator 
is blinded to these scores 
6. After the subject has completed the PR-PCSS ratings, the Investigator will conduct live 
assessments of subject’s cellulite severity of each of the two buttocks using the CR-PCSS 
(section 13.1.2.5); the subject is blinded to these ratings. The ratings from the PR-PCSS 
and CR-PCSS will be used to assess initial eligibility of the buttocks for study entry.  
7. Medical history including EFP history (section 12.1.2.1) 
8. Record prior and concomitant medications/procedures (section 12.8) 
9. Physical examination including measurement of body weight, height, Fitzpatrick skin 
type (section 14.11) 
10. Vital sign measurements (section 14.9) 
11. 12-lead ECG (section 14.10) 
12. Collection of samples for: 
a. Clinical laboratory testing (section 14.7) 
b. Serum pregnancy testing (section 14.7) 
13. Adverse events (section 14) 
12.2. 
Selecting and Marking Dimples during Treatment Visits 
Selection of dimples to be treated in the two buttocks is at the discretion of the Investigator. 
Dimples must be well-defined and evident when the subject is standing in a consistent, 
standardized relaxed pose (without the use of any manipulation such as skin pinching or muscle 
contraction). Each subject will receive 3 treatment visits of study drug according to 
randomization unless the buttock is dimple-free (score of 0 on CR-PCSS as reported by the 
Investigator) at Treatment Visit 2 and/or Treatment Visit 3 (a dimple -free buttock at Treatment 
Visit 1 is precluded by the eligibility criteria); a dimple-free buttock at Treatment Visit 2 and/or 
Treatment Visit 3 does not preclude treatment of the contralateral buttock unless it is dimple-free 
also. During each treatment visit, each of the buttocks will be photographed before and after 
marking dimples and injection sites while the subject is standing in a consistent, standardized 
relaxed pose as described in the Photography Manual. The cellulite severity assessments using 
the PR-PCSS and CR-PCSS will be completed prior to marking dimples and injection sites. 
The Investigator or qualified designee will select dimples within each buttock that are well-
defined, evident when the subject is standing, and suitable for treatment; treatment consists of 
12 injections per buttock (24 injections total in two buttocks) per treatment visit. Because the 
goal of treatment is to improve the aesthetic appearance of each entire buttock, the Investigator 
will be instructed to select dimples that in his or her opinion would most improve the aesthetic 
appearance of each entire buttock. The same dimples within a buttock or different dimples within 
a buttock may be treated at each treatment visit but injections must all be within the buttocks 
(12 injections per buttock) for all 3 visits. Each buttock will receive all 3 treatment visits unless 
the buttock has no treatable EFP dimples and the Investigator rates the buttock a score of 0 on 
the CR-PCSS. If no injections in a particular buttock (right or left) are given at Treatment Visit 

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2, subjects will still be assessed for treatment in the contralateral buttock at Treatment Visit 2, 
and will return for the Day 43 visit and each of the buttocks will again be evaluated by the 
subject (PR-PCSS) and Investigator (CR-PCSS). If the Investigator rates either or both of the 
buttocks greater than 0 on the CR-PCSS, injections at Treatment Visit 3 should be given. 
For each dimple selected for treatment, the Investigator or qualified designee will choose 
injection sites (injection sites within a dimple should be spaced approximately 2 cm apart, if a 
dimple requires more than 1 injection; locating at least one injection site at the nadir, if present, 
of the dimple). Each injection site will be marked with a “dot” using a surgical marker. For 
round dimples, the “dot” will be placed in the center of the dimple; for elongated dimples, “dots” 
will be spaced out approximately 2 cm along the longer axis of the dimple. The Investigator or 
qualified designee will then use a surgical marker to circle each of the dimples selected for 
treatment. Circles in the buttock should not overlap. 
Each of the buttocks will be photographed before and after marking dimples and injection sites 
while the subject is standing in a consistent, standardized relaxed pose as described in the 
Photography Manual. 
Examples of subject dimple and injection site markings are shown as follows: 
Sample Buttock Marking 
 
12.3. 
Digital Photography during Treatment Visits 1, 2, and 3 
During each treatment visit, each of the two buttocks will be photographed before and after 
marking dimples and injections sites while the subject is standing in a consistent, standardized 
relaxed pose as described in section 13.1.1. 

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12.4. 
Treatment Visit 1 (Day 1) 
12.4.1. 
Treatment Visit 1: Pre-Injection 
1. Confirm eligibility criteria 
2. Take digital photography of each of the buttocks before marking dimples and injection 
sites (section 13.1.1) 
3. Subjects will get instruction on the use of the PR-PCSS (Patient Instructions for Use of 
PR-PCSS) 
4. Subjects will rate each of their buttocks using the PR-PCSS (section 13.1.2.1); the 
Investigator is blinded to these ratings 
5. Subjects will complete the Patient Reported Cellulite Impact Scale assessment (PR-CIS; 
section 13.1.2.3): the Investigator is blinded to this rating 
6. The Investigator will conduct live assessments of subject’s cellulite severity of each of 
the buttocks using the CR-PCSS (section 13.1.2.5); the subject is blinded to these ratings. 
The ratings from the PR PCSS and CR-PCSS will be used to assess eligibility for 
randomization 
7. Subjects with PR-PCSS or CR-PCSS ratings in either of the buttocks <3 will be excluded 
from participation 
8. Randomization of subjects with two buttocks eligible for treatment (eligible criteria being 
each buttock have PR-PCSS and CR-PCSS scores of 3 or 4) to treatment (section 12.10); 
obtain kit numbers of study treatment 
9. Record concomitant medications/procedures (section 12.8) 
10. Vital sign measurements (section 14.9) 
11. Collection of samples for: 
a. Anti-AUX-I and anti-AUX-II antibody testing (section 14.8) 
b. Urine pregnancy testing (section 14.7) 
12. Select and mark dimples to be treated in each of the buttocks (section 12.2) 
13. Take digital photograph of each of the buttocks after marking dimples and injection sites 
(section 13.1.1) 
12.4.2. 
Treatment Visit 1: Injection and Post-injection 
1. Administration of study drug in the prone position (section 10.3) 
2. Record number of dimples treated and number of injections administered in each of the 
two buttocks 
3. Vital sign measurements (section 14.9) 
4. Injection site reactions and local tolerability 
5. Adverse events (section 14) 

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12.5. 
Treatment Visit 2 (Day 22 [±3 days]) and Treatment Visit 3 (Day 43 
[±3 days]) 
12.5.1. 
Treatment Visits 2 and 3: Pre-injection 
1. Record concomitant medications/procedures (section 12.8) 
2. Body weight measurements 
3. Vital sign measurements (section 14.9) 
4. Collection of samples for: 
a. Anti-AUX-I and anti-AUX-II antibody testing (section 14.8) 
b. Urine pregnancy testing (section 14.7) 
5. Digital photographs of each of the two buttocks before marking dimples and injection 
sites (section 13.1.1) 
6. Subject Cellulite Assessments of each of the buttocks using the photographic image of 
each buttock before marking dimples and injection sites (NOTE: complete subject 
cellulite assessments before Investigator cellulite assessments) in the following sequential 
order using: 
a. Patient Reported Photonumeric Cellulite Severity Scale (PR-PCSS) assessment 
(section 13.1.2.1); complete this prior to conducting S-GAIS  
b. Subject Global Aesthetic Improvement Scale (S-GAIS) (section 13.1.2.2) 
7. Investigator Cellulite Assessments live of each of the buttocks in the following sequential 
order prior to marking dimples and injection sites using: 
a. Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) live assessment 
of subject (section 13.1.2.5) 
b. Investigator Global Aesthetic Improvement Scale (I-GAIS) (section 13.1.2.6) 
8. Select and mark dimples to be treated in each buttock (section 12.2) 
9. Digital photographs of each buttock after marking dimples and injection sites 
(section 13.1.1)  
10. For eligible buttock(s), obtain kit number(s) of study treatment 
12.5.2. 
Treatment Visits 2 and 3: Injection and Post-injection 
1. Administration of study drug in the prone position (section 10.3) 
2. Record number of dimples treated and number of injections administered in each buttock 
3. Vital sign measurements (section 14.9) 
4. Injection site reactions and local tolerability 
5. Adverse events (section 14) 

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12.6. 
Day 71 (+5 days) End of Study / Early Termination 
The following procedures will be performed on Day 71: 
1. Record concomitant medications/procedures (section 12.8) 
2. Measurement of body weight 
3. Vital sign measurements (section 14.9) 
4. Collection of samples for: 
a. Clinical laboratory testing (section 14.7) 
b. Serum pregnancy test (section 14.7) 
c. Anti-AUX-I and anti-AUX-II antibody testing (section 14.8) 
5. Digital photographs of each of the buttocks 
6. Subject Cellulite Assessment of each of the two buttocks using the photographic image 
before marking dimples and injection sites (NOTE: complete subject cellulite 
assessments before Investigator cellulite assessments) using: 
a. Patient Reported Photonumeric Cellulite Severity Scale (PR-PCSS) assessment 
(section 13.1.2.1) 
b. Subject Global Aesthetic Improvement Scale (S-GAIS) (section 13.1.2.2) 
c. Patient Reported Cellulite Impact Scale (PR-CIS) assessment (section 13.1.2.3); note 
this assessment is of both left and right buttocks rather than each individual buttock 
d. Subject Satisfaction with Cellulite Treatment Assessment (section 13.1.2.4); note this 
assessment is of both left and right buttocks rather than each individual buttock 
7. Investigator Cellulite Assessments of each of the buttocks live using: 
a. Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) live assessment 
of subject (section 13.1.2.5) 
b. Investigator Global Aesthetic Improvement Scale (I-GAIS) (section 13.1.2.6) 
8. Injection site reactions and local tolerability 
9. Adverse events (section 14) 
12.7. 
Unscheduled Visits 
If any subject needs to return to the site prior to her next scheduled visit, site staff should follow 
the Unscheduled Visit procedures outlined in section 5. Site staff may conduct additional study 
procedures if required. 
12.8. 
Prior and Concomitant Medications and Procedures 
All prior medications taken within 90 days before randomization will be recorded. All 
medications (including over-the-counter medications) taken by the subject on Day 1 through the 
end of the study must be recorded. Any prior treatments (medications or procedures) for EFP 
through the end of the study must be recorded on the appropriate eCRF page. 

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Additionally, any diagnostic, therapeutic or surgical procedures performed during the study 
period should be recorded including the date, indication for and description of the procedure. 
12.8.1. 
Prohibited Medications or Procedures 
The following medications are prohibited for randomized subjects during the study: 
anticoagulants (warfarin, heparin, direct thrombin inhibitors, Factor X inhibitors) and antiplatelet 
agents (aspirin >150 mg/day and P2Y12 inhibitors, such as clopidogrel), which can cause 
additional bruising. However the use of aspirin at a dose level of ≤150 mg per day will be 
permitted during study. 
Procedures listed in exclusion criterion #4 (section 11.2, Exclusion Criterion #4) are prohibited 
for randomized subjects during the study. 
Table 4: 
Concomitant Medication Restrictions for Subjects during the Treatment 
Phase of Study 
Drug Class 
Restrictions 
Anticoagulants 
Subjects cannot take antiplatelet agents or anticoagulants (except for 
≤150 mg aspirin daily) within 7 days before and 7 days after the dosing 
administration. 
12.9. 
Treatment Compliance 
Randomized subjects will receive study drug administered by an Investigator at the 
Investigator’s site. 
Accidental or intentional overdoses should be reported to the Sponsor/designee promptly (see 
section 14.6.2.1, Overdose). 
12.10. 
Blinding and Randomization 
On Day 1, if each of the buttocks again meet the criteria (3 or 4 on the PR-PCSS and CR-PCSS) 
the subject will be randomized to a treatment group. The interactive web response system 
(IWRS) will randomly assign each subject to a treatment group (EN3835 0.84 mg per buttock × 
two buttocks or placebo) in a 1:1 ratio within an investigational site. The treatment group will 
remain blinded to the Investigator, subjects, all site personnel, and the sponsor. The IWRS will 
assign the subject study drug kit numbers associated with the randomized treatment. At Day 22 
and 43 visits, the IWRS will again assign the subject study drug kit numbers associated with the 
randomized treatment assigned at Day 1. 
All precautions will be taken to ensure that the blinding of EN3835 and placebo is maintained 
throughout the study period. Unblinding will not be permitted by the study site unless it is 
deemed necessary for treatment of a medical emergency. Before breaking the blind, the 
Investigator should make every attempt to contact the Medical Monitor to discuss the necessity 
of breaking the blind. The study site will have the ability to immediately determine treatment 
identification in the event of an emergency by using the unblinding function within the IWRS, 
however, the Medical Monitor must be notified immediately. The Investigator will be required to 
make a full written explanation of the reason for unblinding the subject and the date. In the event 
that a subject is unblinded prior to contacting the Medical Monitor, the Investigator must provide 

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this information in writing to the Medical Monitor as soon as possible. Breaking the blind at the 
investigative site will immediately disqualify the subject from further participation in the study. 
In addition, the event(s) leading to emergency unblinding must be reported as an SAE according 
to instructions in section 14.5.2, Reporting Serious Adverse Events. 
In addition, it may be necessary for the Investigator or qualified designee to unblind a subject as 
a result of a clinically significant finding noted during safety review by the Investigator, Safety 
Monitor, Medical Monitor and/or qualified designee that might jeopardize subject safety. 
 

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13. 
ASSESSMENT OF EFFICACY 
13.1. 
Efficacy Measurements 
13.1.1. 
Digital Photography  
Although digital photographs are not direct efficacy measurements, digital photography will be 
utilized in the assessment of certain efficacy measurements ie to assess certain cellulite severity 
parameters at specific intervals (see section 5, Schedule of Events). At the Screening visit, the 
Investigator or qualified designee will photograph each buttock using a Sponsor-supplied 
standardized digital camera in a standardized manner. The subject will be standing for each 
photography session and will be wearing a standardized photographic garment as described in 
the Photography Manual. The Investigator or qualified designee will photograph each of the two 
buttocks while the subject is standing in a consistent, standardized relaxed standing pose, 
ie, standing position with relaxed gluteus muscles, at the following time points: 
 Screening (no markings of dimples or injection site) - each of the two buttocks 
 Before and after marking dimples and injection sites (prior to injections) on Days 1, 
22, and 43 - each of the two buttocks 
 During the Day 71 visit (end of study/early termination) (no dimple or injection site 
markings) - each of the two buttocks 
All photographs from this study are the property of Endo and may be utilized for clinical 
development, scientific communication, marketing, regulatory purposes, and/or legal 
applications as required/desired by Endo. 
13.1.2. 
Subject and Investigator Cellulite Assessments 
Investigator cellulite assessments are independent of the subject assessments. Therefore, all 
subject cellulite assessments must be completed before the Investigator’s cellulite assessments 
are initiated. The subject assessments will be done using a subject-assigned password protected 
electronic patient reported outcome (ePRO) system and the Investigator and study site personnel 
will not have access to the subject’s assessments or password; the clinician assessment will be 
recorded in an investigator-assigned password protected system and the subject will not have 
access to the Investigator’s assessments or password. Subject assessments will be done alone 
with no study site personnel in the room. Investigators will be instructed not to verbalize their 
ratings while in the presence of the subject. 
13.1.2.1. Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) 
The PR-PCSS will be conducted for the purpose of assessing the severity of cellulite in the 
buttock. The scale is a 5-level photonumeric scale developed specifically for patients and used 
by the subject to assess the severity of their cellulite in the buttocks by viewing digital images of 
each of their buttocks captured by photography at the visit; the ratings range from 0 (None) to 
4 (Severe) with labels and descriptors to aid the subject in the assessments.  

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At Screening and at the beginning of their visits on Day 1, Day 22, Day 43, and Day 71, subjects 
will have digital photographs taken of each of their two buttocks. Subjects will be given 
instructions in the proper use (Patient Instructions for Use of PR-PCSS) of the PR-PCSS and 
then perform the PR-PCSS for each of the buttocks (Appendix B). While viewing the digital 
images of each of their buttocks on a standardized computer monitor and using PR-PCSS for 
buttock, subjects will be instructed to answer the following question for each buttock: Today, 
how would you rate the severity of your cellulite in the area displayed using the PR-PCSS? The 
subject will be given the following explanations: Please try to match the severity of your 
cellulite, as seen in this digital image, with one of the cellulite levels on the PR-PCSS. Please 
look at the image of your cellulite and the pictures, labels, and descriptions on the PR-PCSS 
carefully before selecting your answer. If you feel that your cellulite level is between 2 of the 
levels, please select the level that is closest to your image. If you feel that your cellulite is exactly 
halfway between two PR-PCSS levels of cellulite severity, please select the more severe 
response. 
The subject will enter their rating electronically into an ePRO system; the Investigator and other 
site personnel will be blinded to the rating entered by the subject. This variable will be entered 
directly into the EDC system, thus the electronic database will serve as the direct point of data 
capture and will serve as source for this variable. 
13.1.2.2. Subject Global Aesthetic Improvement Scale (S-GAIS) 
Subjects will complete the S-GAIS for each of the buttocks as described below at the Day 22, 
Day 43, and Day 71 study visits using the pre-treatment Day 1 digital image (Baseline) of each 
of the buttocks for comparison. 
All treated subjects will be instructed to answer the following question for each buttock:  
How would you rate the appearance of your treated cellulite after treatment? 
The S-GAIS assessment will occur after the subject has completed the PR-PCSS assessment to 
avoid introducing potential bias to the static PR-PCSS assessment. The subject will view each of 
their pre-treatment Day 1 digital images alongside their Day 22, Day 43 or Day 71/End of study 
visit digital images of each of their buttocks to aid in the assessment (Table 5). Subjects will 
provide a rating from those below that best represents their answer for each treated buttock. 
This variable will be entered directly into the EDC system, thus the electronic database will serve 
as the direct point of data capture and will serve as source for this variable. 
 
 

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Table 5: 
Subject Global Aesthetic Improvement Scale (S-GAIS) 
Rating 
Response Option 
Description 
+3 
Very much improved 
My treated cellulite looks very much better. 
+2 
Much improved 
My treated cellulite looks much better, but additional treatment 
would slightly improve the result. 
+1 
Improved 
My treated cellulite looks better, but additional treatment is 
necessary. 
0 
No change 
My treated cellulite looks essentially the same as it did 
originally. 
−1 
Worse 
My treated cellulite looks worse than it did originally. 
−2 
Much worse 
My treated cellulite looks much worse than it did originally. 
−3 
Very much worse 
My treated cellulite looks very much worse than it did 
originally. 
13.1.2.3. Patient Reported Cellulite Impact Scale (PR-CIS) 
At the Day 1 visit and the Day 71 visit, subjects will be instructed to answer 6 questions related 
to the areas selected for treatment on their buttocks on the PR-CIS (Appendix D) while viewing 
digital images of their buttocks. The PR-CIS assesses the visual and emotional impact of cellulite 
(happy, bothered, self-conscience, embarrassed, looking older, or looking overweight or out of 
shape) using a 6-question survey, with each question rated on a numerical rating scale from 
0 (not at all) to 10 (extremely). 
This variable will be entered directly into the EDC system, thus the electronic database will serve 
as the direct point of data capture and will serve as source for this variable. 
13.1.2.4. Subject Satisfaction with Cellulite Treatment Assessment 
At the Day 71 visit, subjects will be instructed to answer a question related to their treated 
buttocks. Subjects will be given a list of responses and they will provide a rating from those 
below that best represents their answer (Table 6). 
Today, how satisfied are you with the results of the cellulite treatment you received on the 
specific area or areas on your buttocks that were treated? 
This variable will be entered directly into the EDC system, thus the electronic database will serve 
as the direct point of data capture and will serve as source for this variable. 
Table 6: 
Subject Satisfaction with Cellulite Treatment Assessment - Buttocks 
Rating 
Description 
+2 
I am very satisfied with the cellulite treatment on my buttocks. 
+1 
I am satisfied with the cellulite treatment on my buttocks. 
0 
I am neither dissatisfied nor satisfied with the cellulite treatment on my buttocks. 
-1 
I am dissatisfied with the cellulite treatment on my buttocks. 
-2 
I am very dissatisfied with the cellulite treatment on my buttocks. 

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13.1.2.5. Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 
The CR-PCSS will be conducted for the purpose of assessing the severity of cellulite in the 
buttock. The scale is a 5-level photonumeric scale developed specifically for clinicians and used 
by the Investigator to assess the severity of the subject’s cellulite in each buttock by live 
assessments; the ratings range from 0 (None) to 4 (Severe) with labels and descriptors to aid the 
Investigator in the assessments. 
Investigators will be trained and qualified on the use of the CR-PCSS prior to assessing any 
subjects. 
At the Screening visit, the Investigator will determine severity of cellulite of each of the 
two buttocks via live assessment of the subject using the CR-PCSS for buttock (Appendix C) 
after the subject has completed her self-assessment using the PR-PCSS. Before injections on 
treatment visits Day 1, Day 22, and Day 43, and on visit Day 71; Investigators will evaluate each 
of the two buttocks by live assessments using the CR-PCSS for the buttock to make his/her 
evaluation. At each visit, the Investigator will make his/her assessment independently and after 
the subject has conducted her self-assessment using the PR-PCSS. 
This variable will be entered directly into the EDC system, thus the electronic database will serve 
as the direct point of data capture and will serve as source for this variable. 
13.1.2.6. Investigator Global Aesthetic Improvement Scale (I-GAIS) 
On the Day 22, Day 43, and Day 71 study visits, the Investigator will determine the degree of 
improvement of each buttock by comparing the cellulite from the Day 1 pre-treatment (Baseline) 
digital image of each buttock to the cellulite seen in a live assessment (Table 7). The I-GAIS 
assessment will occur after the CR-PCSS assessment (section 13.1.2.5) to avoid introducing 
potential bias to the static CR-PCSS assessment by the Investigator. For each buttock, the 
Investigator will provide the rating from those below that best represents his/her answer. 
This variable will be entered directly into the EDC system, thus the electronic database will serve 
as the direct point of data capture and will serve as source for this variable. 
Table 7: 
Investigator Global Aesthetic Improvement Scale (I-GAIS) 
Rating 
Response Option 
Description 
+3 
Very much improved 
Optimal cosmetic result from treatment of the treated dimples 
+2 
Much improved 
Marked improvement in the treated area appearance from 
before treatment, but not completely optimal 
+1 
Improved 
Obvious improvement in the treated area appearance from 
before treatment, but additional treatment is indicated 
0 
No change 
The treated area appearance is essentially the same as before 
treatment 
−1 
Worse 
The treated area appearance is worse than before treatment 
−2 
Much worse 
Marked worsening in appearance from the initial condition 
−3 
Very much worse 
Obvious worsening in appearance from the initial condition 

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14. 
ASSESSMENT OF SAFETY 
14.1. 
Definitions 
14.1.1. 
Adverse Events 
An adverse event (AE) is any unfavorable or unintended change in body structure (signs), body 
function (symptoms), laboratory result (eg, chemistry, ECG, X-ray, etc.), or worsening of a 
pre-existing condition associated temporally with the use of the study medication whether or not 
considered related to the study medication. Adverse events will be captured once a subject has 
signed the informed consent. AEs include: 
 Changes in the general condition of the subject 
 Subjective symptoms offered by or elicited from the subject 
 Objective signs observed by the Investigator or other study personnel 
 All concurrent diseases that occur after the start of the study, including any change in 
severity or frequency of pre-existing disease 
 All clinically relevant laboratory abnormalities or physical findings that occur during 
the study 
A treatment-emergent adverse event (TEAE) is any condition that was not present prior to 
treatment with study medication but appeared following treatment, was present at treatment 
initiation but worsened during treatment, or was present at treatment initiation but resolved and 
then reappeared while the individual was on treatment (regardless of the intensity of the AE 
when the treatment was initiated). 
All AEs, including both observed or volunteered problems, complaints, signs or symptoms must 
be recorded on the AE page of the eCRF, regardless of whether associated with the use of study 
medication. This would include AEs resulting from concurrent illness, reactions to concurrent 
medication use, or progression of disease states (excluding the disease under study). A condition 
present at baseline that worsens after initiation of study treatment will be captured as an AE; the 
onset date will be the date the event worsened. The AE should be recorded in standard medical 
terminology when possible. 
14.1.2. 
Serious Adverse Events 
A serious adverse event (SAE) is defined as an AE that: 
 Results in death 
 Is immediately life-threatening (there is an immediate risk of death from the AE as it 
occurred; this does not include an AE that had it occurred in a more serious form may 
have caused death) 
 Results in or prolongs an inpatient hospitalization (Note: a hospitalization for elective 
or pre-planned surgery, procedure, or drug therapy does not constitute an SAE) 

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 Results in permanent or substantial disability (permanent or substantial disruption of 
one’s ability to conduct normal life functions) 
 Is a congenital anomaly/birth defect (in offspring of a subject using the study 
medication regardless of time to diagnosis) 
 Is considered an important medical event 
Important medical events are defined as events that, based upon appropriate medical judgment, 
may jeopardize the subject and may require medical or surgical intervention to prevent one of the 
other serious outcomes. Examples of important medical events include malignancy, allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias 
or convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
14.2. 
Monitoring Adverse Events 
At each visit, subjects will be queried regarding any AEs that have occurred since the last visit. 
Subjects will be asked to volunteer information concerning AEs with a non-leading question 
such as, “How do you feel?” Study site personnel will then record all pertinent information in the 
source documents and the eCRF. The study drug compliance record should also be reviewed to 
detect potential overdoses (intentional/unintentional). 
14.3. 
Relationship to Study Drug 
The degree of “relatedness” of the AE to the study medication must be described using the 
following scale: 
 Not related indicates that the AE is definitely not related to the study medication. 
 Unlikely related indicates that there are other, more likely causes and study 
medication is not suspected as a cause. 
 Possibly related indicates that a direct cause and effect relationship between study 
medication and the AE has not been demonstrated, but there is evidence to suggest 
there is a reasonable possibility that the event was caused by the study medication. 
 Probably related indicates that there is evidence suggesting a direct cause and effect 
relationship between the AE and the study medication. 
It is the Sponsor’s policy to consider “Probably related” and “Possibly related” causality 
assessments as positive causality. “Not related” and “Unlikely related” causality assessments are 
considered as negative causality. 
Assessments will be recorded on the eCRF and must indicate clearly the relationship being 
assessed. For example, an AE that appears during a placebo run-in phase would be assessed with 
respect to the placebo treatment received and/or study procedures conducted during this phase. If 
the AE continued into an active treatment phase, the relationship would be assessed for the active 
treatment phase only if the AE worsened. 

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14.4. 
Intensity Assessment 
The intensity (or severity) of AEs is characterized as mild, moderate, or severe: 
 Mild AEs are usually transient, requiring no special treatment, and do not interfere 
with the subject’s daily activities. 
 Moderate AEs introduce a low level of inconvenience or concern to the subject and 
may interfere with daily activities, but are usually ameliorated by simple therapeutic 
measures. 
 Severe AEs interrupt a subject’s usual daily activity and typically require systemic 
drug therapy or other treatment. 
When the intensity category of an AE changes, the greatest intensity during that continuous 
episode should be recorded. 
14.5. 
Reporting Adverse Events and Serious Adverse Events 
14.5.1. 
Reporting Adverse Events 
Throughout the study, AEs will be documented on the source document and on the appropriate 
page of the eCRF whether or not considered treatment-related. This includes any new signs, 
symptoms, injury or illness, including increased severity of previously existing signs, symptoms, 
injury, or illness. Conditions existing prior to screening will be recorded as part of the subject’s 
medical history. The Investigator is responsible for assessing the relationship of AEs to the study 
medication; relationship will be classified as not related, unlikely related, possibly related, or 
probably related. 
All AEs will be collected by the Investigator from the time of signing the informed consent 
through 28 days after the last dose of study medication; this includes any AEs that are ongoing at 
the time of completion/termination of the study. All ongoing AEs must be followed until 
resolution or for 30 days after the subject’s last study visit, whichever comes first. 
14.5.2. 
Reporting Serious Adverse Events 
Any SAE, including death resulting from any cause, which occurs to any subject participating in 
this study must be reported via email or fax by the Investigator using the Endo Clinical Trial 
Report Form for SAEs within 24 hours of first becoming aware of the SAE. SAEs will be 
collected by the Investigator from the time of signing the informed consent through 28 days after 
the last dose of study medication. SAEs that occur within 28 days, following cessation of the 
study treatment, or within 30 days, following premature discontinuation from the study for any 
reason, must also be reported within the same timeframe. Any SAE that is felt by the Investigator 
to be related to the study medication must be reported regardless of the amount of time since the 
last dose received. Follow-up information collected for any initial report of an SAE must also be 
reported to the Sponsor within 24 hours of receipt by the Investigator. 
All SAEs will be followed until resolution, stabilization of condition, or until follow-up is no 
longer possible. 

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In the event discussion is necessary regarding treatment of a subject, call the Medical 
Monitor (see contact information in section 3). 
All SAEs should be sent via the email address, or faxed to the fax number, provided in 
section 3. 
The Sponsor will determine whether the SAE must be reported within 7 or 15 days to regulatory 
authorities in compliance with local and regional law. If so, the Sponsor (or the Sponsor’s 
representative) will report the event to the appropriate regulatory authorities. The Investigator 
will report SAEs to the IRB per their IRB policy. 
14.5.2.1. Follow-up Procedures for Serious Adverse Events 
To fully understand the nature of any SAE, obtaining follow-up information is important. 
Whenever possible, relevant medical records such as discharge summaries, medical 
consultations, and the like should be obtained. In the event of death, regardless of cause, all 
attempts should be made to obtain the death certificate and any autopsy report. These records 
should be reviewed in detail, and the Investigator should comment on any event, lab 
abnormality, or any other finding, noting whether it should be considered a serious or 
non-serious AE, or whether it should be considered as part of the subject’s history. In addition, 
all events or other findings determined to be SAEs should be identified on the follow-up SAE 
form and the Investigator should consider whether the event is related or not related to study 
drug. 
14.6. 
Special Reporting Situations 
14.6.1. 
Adverse Events of Special Interest 
Adverse events such as bruising, ecchymosis, hematomas, and contusions that occur remote to 
the site of drug administration, or any hypersensitivity reactions, including anaphylaxis, will be 
recorded as an AE or SAE as appropriate (see section 14.1.1, Adverse Events or section 14.1.2, 
Serious Adverse Events). 
14.6.2. 
Overdose/Misuse/Abuse 
14.6.2.1. Overdose 
Study drug overdose is any accidental or intentional use of study drug in an amount higher than 
the dose indicated by the protocol for that subject. Study drug compliance (see section 12.9) 
should be reviewed to detect potential instances of overdose (intentional or accidental). 
Any study drug overdose during the study should be noted on the study medication eCRF. 
An overdose is not an AE per se, however all AEs associated with an overdose should both be 
entered on the Adverse Event eCRF and reported using the procedures detailed in section 14.5.2, 
Reporting of Serious Adverse Events, even if the events do not meet seriousness criteria. If the 
AE associated with an overdose does not meet seriousness criteria, it must still be reported using 
the Endo Clinical Trial Report Form for SAEs and in an expedited manner, but should be noted 
as non-serious on the form and the Adverse Event eCRF. 

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14.6.3. 
Pregnancy 
Subjects should be instructed to immediately notify the Investigator of any pregnancies. 
Any pregnancy that occurs in a subject during this clinical study will be reported for tracking 
purposes only. All subject pregnancies that are identified during or after this study, where the 
estimated date of conception is determined to have occurred during study drug therapy or within 
28 days of the last dose of study medication need to be reported, followed to conclusion, and the 
outcome reported, even if the subject is discontinued from the study. The Investigator should 
report all pregnancies within 24 hours using the Initial Pregnancy Report Form, and any 
pregnancy-associated SAE using the SAE report form, according to the usual timelines and 
directions for SAE reporting provided in section 14.5.2. Monitoring of the pregnancy should 
continue until conclusion of the pregnancy; 1 or more Follow-up Pregnancy Report Form(s) 
detailing progress, and a Two Month Follow-up Pregnancy Report Form detailing the outcome, 
should be submitted. 
Pregnancy itself is not regarded as an AE unless there is suspicion that the investigational 
product under study may have interfered with the effectiveness of a contraceptive medication. 
Likewise, elective abortions without complications are not considered AEs. Any SAEs 
associated with pregnancy (eg, congenital abnormalities/birth defects/spontaneous miscarriages 
or any other serious events) must additionally be reported as such using the SAE report form. 
Spontaneous miscarriages should also be reported and handled as SAEs. 
A subject who becomes pregnant must be withdrawn from the study. Attempts to obtain the 
pregnancy follow-up and pregnancy outcome information detailed above are necessary even if a 
subject discontinues treatment because of pregnancy. 
14.6.4. 
AEs/SAEs Experienced by Non-subjects Exposed to Study Medication 
Non-subjects are persons who are not enrolled in the study but have been exposed to study 
medication, including instances of diversion of study medication. All such AEs/SAEs occurring 
in non-subjects from such exposure will be reported to the Endo PVRM Department (when the 
non-subject agrees) on the departmental form for serious adverse experiences regardless of 
whether the event is serious or not. Instructions for completing the form for events experienced 
by non-subjects will be provided. SAEs occurring in non-subjects exposed to study medication 
will be processed within the same SAE reporting timelines as described in section 14.5.2, 
Reporting Serious Adverse Events. Additionally, the drug accountability source documentation 
at the site should reflect this occurrence. 
14.7. 
Clinical Laboratory Determinations 
Clinical laboratory tests will be conducted according to the Schedule of Events (section 5). 
Clinical laboratory tests will be performed by a designated central laboratory. Each site will be 
provided with instructions on specimen collection, preparation, packaging and transport. Refer to 
the central laboratory manual for further information regarding sample collection, handling, and 
labeling. The results of the tests will be returned to the investigational sites.  

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Clinical laboratory test data will be reviewed by the Investigator, or designee, and additional 
clinical laboratory tests may be ordered at his/her discretion (eg, if the results of any clinical 
laboratory test falls outside the reference range or clinical symptoms necessitate additional 
testing to ensure safety). Any additional testing will be performed by the designated central 
laboratory. The Investigator or qualified designee must acknowledge the review of laboratory 
results. 
The Investigator will review all abnormal lab results for potentially clinically important. Any 
abnormal clinical laboratory test result meeting the Investigator’s criteria for potentially 
clinically important (refer to central laboratory manual) will be recorded as an AE or SAE as 
appropriate (see section 14.1.1, Adverse Events, and section 14.1.2, Serious Adverse Events). 
Laboratory results will be sent electronically to Endo Pharmaceuticals Inc. for data management. 
Clinical laboratory parameters that will be measured in this study are listed in Table 8. 
Table 8: 
Clinical Laboratory Tests 
Hematology 
Biochemistry 
Urinalysis 
Hemoglobin 
Glucose 
Glucose 
Hematocrit 
Sodium 
Protein 
Red blood cell 
Potassium 
Specific gravity 
White blood cell (WBC) 
Calcium 
pH 
Platelets 
Chloride 
Ketones 
WBC Differential 
CO2 
Bilirubin 
Inorganic phosphate 
Urobilinogen 
Blood urea nitrogen 
Nitrite 
Creatinine 
Blood* 
Creatinine clearance (estimated) 
Leukocytes* 
Aspartate transaminase (AST) 
Alanine transaminase (ALT) 
Gamma-glutamyl transferase (GGT) 
Total bilirubin (TBL) (direct bilirubin reflex if elevated) 
Albumin 
Alkaline phosphatase (ALP) 
Uric acid 
* Microscopic examination will be performed if blood or leukocytes are detected by dipstick.
For women of childbearing potential, a serum pregnancy test will be performed at Screening and 
Day 71/End of Study/Early Termination, and urine pregnancy tests will be performed at Day 1, 
Day 22, and Day 43 (refer to section 5). Female subjects of childbearing potential must have a 
negative pregnancy test at the Screening Visit and at Day 1 (Baseline), Day 22, and Day 43 to be 
randomized and/or receive treatment in the study. If necessary, additional urine pregnancy tests 
can be performed at any time during the study at the discretion of the Investigator. Urine 
pregnancy test kits will be supplied by the Sponsor. 

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14.11. 
Physical Examination 
A complete physical examination will be performed at the Screening Visit. All examinations will 
be performed by a physician or health professional listed on the Form FDA 1572 and licensed to 
perform physical examinations. Height and body weight will be measured and recorded at 
screening. 
The Investigator will review all physical exam findings for clinical significance. Any physical 
exam finding meeting the Investigator’s or Sponsor’s criteria for clinical significance will be 
recorded as an AE or SAE as appropriate (see section 14.1.1, Adverse Events and section 14.1.2, 
Serious Adverse Events). 
At screening, the Investigator will also assess the subject’s skin type using the Fitzpatrick 
scale (Table 10). Only the Fitzpatrick Scale shown below may be used during the study. 
Table 10: 
Fitzpatrick Scale 
I 
Pale white skin, blue/hazel eyes, blond/red hair 
Always burns, does not tan 
II 
Fair skin, blue eyes 
Burns easily, tans poorly 
III 
Darker white skin 
Tans after initial burn 
IV 
Light brown skin 
Burns minimally, tans easily 
V 
Brown skin 
Rarely burns, tans darkly easily 
VI 
Dark brown or black skin 
Never burns, always tans darkly 
Follow-up body weight will be measured before injection on Day 22 and Day 43 and at the 
Day 71 visit. 
14.12. 
Other Safety Assessments 
Not applicable. 

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15. 
ASSESSMENT OF PHARMACOKINETICS 
Not applicable. 

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16. 
ASSESSMENT OF PHARMACODYNAMICS 
Not applicable. 

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17.2.2. 
Intent-to-Treat (ITT) Population 
The ITT population is defined as all randomized subjects who have received at least one 
injection of study medication. All demographic and baseline characteristic summaries will be 
based on this population. The primary and key secondary efficacy parameters will be 
summarized based on this population. 
17.2.3. 
Modified Intent-to-Treat (mITT) Population 
The mITT population is defined as all intent-to-treat subjects with a baseline and at least 1 
post-injection evaluation of both the Investigator CR-PCSS and subject PR-PCSS for both left 
and right buttocks. All secondary and supportive efficacy evaluations will be based on the mITT 
population. 
17.2.4. 
Per-Protocol (PP) Population 
The per-protocol population is defined as the mITT subjects without any major protocol 
deviation that will impact the subject’s efficacy and safety. This population may be used in the 
efficacy sensitivity analysis. 
17.3. 
Subject Disposition 
The number of subjects included in each study population will be summarized by treatment 
group. Subjects excluded from the safety and efficacy (eg, ITT) populations will be listed by 
treatment group. 
The number and percentage of subjects completed and prematurely discontinued during the 
treatment period will be presented for each treatment group and pooled across treatment groups. 
Screen failures (ie, screened but not randomized subjects) and the associated failure reasons will 
be tabulated overall. Reasons for premature discontinuation from the treatment period as 
recorded on the termination page of the eCRF will be summarized (number and percentage) by 
treatment group for all randomized subjects. Percentage of premature discontinuations will be 
compared between treatment groups. 
17.4. 
Demographics and Other Baseline Characteristics 
The summarization of demographic variables (eg, age, sex, race, weight, height, and body mass 
index [BMI]), medical and surgical history, and other baseline characteristics relevant to the 
indication studied in the study will be described. 
Demographic characteristics, including sex, age, age group, race, height, and weight, will be 
summarized by treatment group, for the ITT population, using descriptive statistics. All 
screening characteristics and medical information will also be summarized by treatment group 
using descriptive statistics. The descriptive summaries will include frequency tables for all 
categorical response variables and n, mean, standard deviation (SD), median, minimum and 
maximum for all continuous variables. 

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17.5. 
Efficacy Analyses 
All efficacy endpoints including supportive efficacy analysis will be summarized as percentages. 
The dichotomous secondary endpoints (ie, responder endpoints) will be analyzed using a 
Cochran-Mantel-Haenszel test adjusted for Investigator. Changes in the PR-PCSS ratings and 
CR-PCSS ratings from baselines, S-GAIS scores, and I-GAIS scores will be analyzed using the 
Wilcoxon rank sum test. All the tests are two-sided. 
The primary endpoint will be summarized as percentages and analyzed using a Cochran-Mantel-
Haenszel test that compares the 2 treatment groups and adjusts for Investigator at a level of 
significance of 0.05 based on the ITT population. Any subject who does not have an evaluation 
of CR-PCSS and/or PR-PCSS at Day 71 will be classified as a non-responder. 
The key secondary efficacy analyses will be analyzed in the same manner as the primary 
endpoint based on the ITT population. Any subject who does not have an evaluation at Day 71 
will be classified as a non-responder for the analyses. The family #1 key secondary efficacy 
analyses will be performed only if the primary efficacy analysis is significant (p ≤ 0.05; 
gatekeeping strategy). Similarly family #2 key secondary efficacy analyses will be performed 
only if at least one of the key secondary efficacy endpoints of family #1 is significant (p ≤ 0.025; 
parallel gatekeeping strategy). Within a family of key secondary efficacy endpoints, Bonferroni 
method will be performed to relocate unused alpha for testing each endpoint to assure an overall 
error rate of p ≤ 0.05. The details of the testing procedures will be provided in the statistical 
analysis plan for the study. 
All supportive endpoints will be summarized as subject counts and percentages for categorical 
data or n, mean, SD, median, minimum, and maximum for continuous data. All the supportive 
analyses will be performed based on all observed data (ie, missing data not imputed) in the mITT 
population at all visits without multiplicity adjustment. This analysis will also be performed at 
Day 71 with missing data at Day 71 imputed by a last observation carried forward (LOCF) 
approach if subjects have at least one post-dose assessment. The dichotomous secondary 
endpoints (ie, responder endpoints) will be analyzed using a Cochran-Mantel-Haenszel test 
adjusted for Investigator. Changes in the PR-PCSS ratings and CR-PCSS ratings from baselines, 
S-GAIS scores, and I-GAIS scores will be analyzed using the Wilcoxon rank sum test. Changes 
in PR-CIS from baselines will be analyzed using an analysis of covariance (ANCOVA) adjusted 
for baseline values 
17.5.1. 
Primary Efficacy Variable 
The primary efficacy variable is the proportion of 2-level composite responders at Day 71 
defined as subjects with at least one of two treated buttocks with: 
 an improvement in severity from baseline (Day 1 visit) of at least 2 levels of severity 
in the CR-PCSS as assessed live by the Investigator, and  
 an improvement in severity from baseline of at least 2 levels of severity in the 
PR-PCSS by the subject while viewing the digital image of the same buttock. 

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A subject will be considered a responder if these criteria are met in either the left buttock or right 
buttock or both buttocks in that subject. In other words, a subject will be considered a responder 
if she has an improvement of at least 2 levels on the PR-PCSS and an improvement of at least 
2 levels on the CR-PCSS on that same buttock; that buttock could be the left buttock or right 
buttock or both buttocks. 
Sensitivity analyses for the primary endpoint will include: 
 ITT subjects with missing data handled by multiple imputation (MI) approach 
 ITT subjects with missing data handled by an LOCF approach 
 mITT subjects with missing data handled by an LOCF approach 
 Observed data only (no missing data handling) 
 Per-protocol (PP) subjects with missing data handled by an LOCF approach if 10% or 
more subjects are excluded in the PP population from mITT population 
17.5.2. 
Secondary Efficacy Variables 
17.5.2.1. Key Secondary Variables 
There will be 4 key secondary endpoints grouped in two families of 2 endpoints per family 
analyzed in a hierarchical order. 
 Family #1 – two endpoints: 
 Proportion of 1-level PR-PCSS responders defined as subjects with ≥1-level 
improvement in PR-PCSS severity rating of left buttock at Day 71 compared to 
Day 1 
 Proportion of 1-level PR-PCSS responders defined as subjects with ≥1-level 
improvement in PR-PCSS severity rating of right buttock at Day 71 compared to 
Day 1 
 Family #2 – two endpoints: 
 Proportion of 1-level S-GAIS responders defined as subjects with ≥1-level 
improvement (improved, much improved or very much improved) in the S- GAIS 
assessment of left buttock at Day 71 
 Proportion of 1-level S-GAIS responders defined as subjects with ≥1-level 
improvement (improved, much improved or very much improved) in the S-GAIS 
assessment of right buttock at Day 71 

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17.5.3. 
Supportive Efficacy Variables 
17.5.3.1. Supportive Variables 
The supportive variables will evaluate assessments at various study time points and using various 
populations. 
 Proportion of 2-level PR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 2 levels of severity in the PR-PCSS of the left 
buttock (Days 22, 43, and 71) 
 Proportion of 2-level PR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 2 levels of severity in the PR-PCSS of the right 
buttock (Days 22, 43, and 71) 
 Proportion of 1-level PR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 1 level of severity in the PR-PCSS of left buttock 
(Days 22, 43, and 71) 
 Proportion of 1-level PR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 1 level of severity in the PR-PCSS of right 
buttock (Days 22, 43, and 71) 
 Proportion of 2-level PR-PCSS responders of at least one buttock (Days 22, 43, and 
71). A subject will be considered a responder if this criterion is met in the left buttock 
or right buttock or both buttocks in that subject. 
 Proportion of 1-level PR-PCSS responders of at least one buttock (Days 22, 43, and 
71). A subject will be considered a responder if this criterion is met in the left buttock 
or right buttock or both buttocks in that subject. 
 Proportion of 2-level PR-PCSS responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both left and right buttocks. 
 Proportion of 1-level PR-PCSS responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both left and right buttocks. 
 Proportion of 2-level CR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 2 levels of severity in the CR-PCSS of the left 
buttock (Days 22, 43, and 71) 
 Proportion of 2-level CR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 2 levels of severity in the CR-PCSS of the right 
buttock (Days 22, 43, and 71) 
 Proportion of 1-level CR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 1 level of severity in the CR-PCSS of the left 
buttock (Days 22, 43, and 71) 

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 Proportion of 1-level CR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 1 level of severity in the CR-PCSS of the right 
buttock (Days 22, 43, and 71) 
 Proportion of 2-level CR-PCSS responders of at least one buttock (Days 22, 43, and 
71). A subject will be considered a responder if this criterion is met in the left buttock 
or right buttock or both buttocks in that subject. 
 Proportion of 1-level CR-PCSS responders of at least one buttock (Days 22, 43, and 
71). A subject will be considered a responder if this criterion is met in the left buttock 
or right buttock or both buttocks in that subject. 
 Proportion of 2-level CR-PCSS responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both left and right buttocks. 
 Proportion of 1-level CR-PCSS responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both left and right buttocks. 
 Proportion of 1-level composite responders of the left buttock (defined as subjects 
with an improvement in severity from baseline of at least 1 level of severity in the 
CR-PCSS of the left buttock assessed live by the Investigator and an improvement of 
severity from baseline of at least 1 level of severity in the PR-PCSS of that same left 
buttock) (Days 22, 43, and 71) 
 Proportion of 1-level composite responders of the right buttock (defined as subjects 
with an improvement in severity from baseline of at least 1 level of severity in the 
CR-PCSS of the right buttock assessed live by the Investigator and an improvement 
of severity from baseline of at least 1 level of severity in the PR-PCSS of that same 
right buttock) (Days 22, 43, and 71) 
 Proportion of 1-level composite responders of at least one buttock (Days 22, 43, and 
71). A subject will be considered a responder if this criterion is met in the left buttock 
or right buttock or both buttocks in that subject. 
 Proportion of 1-level composite responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both left and right buttocks. 
 Proportion of 2-level composite responders of the left buttock (defined as subjects 
with an improvement in severity from baseline of at least 2 levels of severity in the 
CR-PCSS of the left buttock assessed live by the Investigator and an improvement of 
severity from baseline of at least 2 levels of severity in the PR-PCSS of that same left 
buttock) (Days 22, 43, and 71) 
 Proportion of 2-level composite responders of the right buttock (defined as subjects 
with an improvement in severity from baseline of at least 2 levels of severity in the 
CR-PCSS of the right buttock assessed live by the Investigator and an improvement 
of severity from baseline of at least 2 levels of severity in the PR-PCSS of that same 
right buttock) (Days 22, 43, and 71) 

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 Proportion of 2-level composite responders of at least one of two buttocks (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in the left 
buttock or right buttock or both buttocks in that subject.  
 Proportion of 2-level composite responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both left and right buttocks. 
 Proportion of subjects at each level of the S-GAIS of the left buttock (Days 22, 43, 
and 71) 
 Proportion of subjects at each level of the S-GAIS of the right buttock (Days 22, 43, 
and 71) 
 Proportion of 1-level S-GAIS responders defined as subjects with a response of at 
least 1 (improved) in the S- GAIS of the left buttock (Days 22, 43, and 71) 
 Proportion of 1-level S-GAIS responders defined as subjects with a response of at 
least 1 (improved) in the S- GAIS of the right buttock (Days 22, 43, and 71) 
 Proportion 1-level S-GAIS responders of at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if this criterion is met in the left buttock or 
right buttock or both buttocks in that subject. 
 Proportion of 1-level S-GAIS responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both left and right buttocks. 
 Proportion of subjects at each level of the I-GAIS of the left buttock (Days 22, 43, 
and 71) 
 Proportion of subjects at each level of the I-GAIS of the right buttock (Days 22, 43, 
and 71) 
 Proportion of 1-level I-GAIS responders (defined as subjects with a response of at 
least 1 (improved) in the Investigator GAIS assessment) of at least one buttock 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in the left buttock or right buttock or both buttocks in that subject.  
 Proportion of 1-level I-GAIS responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both left and right buttocks.  
 Change from baseline (Day 1) of the PR-CIS total score at Day 71 
 Change from baseline (Day 1) of the abbreviated PR-CIS score at Day 71 
 Proportion of subjects with a change from baseline (Day 1) of the PR-CIS ≥ 12 at 
Day 71 
 Proportion of subjects with a change from baseline (Day 1) of the abbreviated 
PR-CIS ≥ 10 at Day 71 

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 Proportion of subjects at each level of the subject satisfaction with cellulite treatment 
(Day 71) 
 Proportion of satisfied responders (defined as subjects with a response of at least 1 
(ie, 1-Satisfied or 2-Very Satisfied) in the subject satisfaction with cellulite treatment 
assessment (Day 71) 
17.6. 
Safety Analyses 
Safety variables include adverse events, laboratory parameters, vital signs, ECG parameters, and 
physical examinations. For each safety parameter, the last assessment made prior to the first dose 
of study drug will be used as the baseline for all analyses of that safety parameter. 
17.6.1. 
Prior, Concomitant, and Follow-up Medication 
The World Health Organization (WHO) Drug Dictionary will be used to classify prior and 
concomitant medications by therapeutic class. Prior medication will be defined as any 
medication taken prior to the first dose of study drug. Concomitant medication is defined as any 
medication taken on or after the date of first dose of study drug. 
Prior and concomitant medication use will be summarized descriptively by the number and 
percentage of subjects for each preferred term (generic name from WHO dictionary) by 
treatment. Multiple use of the same medication by a subject will be counted only once. 
17.6.2. 
Study Drug Exposure 
The following information regarding treatment will be summarized per each treated buttock by 
treatment group: 
 Total number of treatment visits 
 Number of subjects who had treatment session done or treatment session not done at 
each treatment visit 
 For subjects who had the treatment session done, the number of subjects who got all 
24 injections at the treatment visit or who received less than 24 injections 
 Number of injections given at each treatment visit  
 Number of dimples treated at each treatment visit  
 Average number of injections per dimple at each treatment visit  
Subjects who did not receive all 3 treatment visits and who did not receive 24 injections at a 
treatment visit will be listed. 
17.6.3. 
Measurement of Treatment Compliance 
Not applicable (the study drug is administered at the site by the study investigator). 
17.6.4. 
Adverse Events 
The Medical Dictionary for Regulatory Activities (MedDRA) will be used to code AEs. 

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An AE (classified by preferred term) that started on or after the date of the first dose of the study 
drug will be considered a TEAE if it was not present prior to the first dose of study drug, or was 
present prior to the first dose of study drug but increased in intensity during the treatment period. 
If more than 1 AE is reported prior to the first dose of study drug and coded to the same 
preferred term, then the AE with the greatest intensity will be used as the benchmark for 
comparison to the AEs occurring during the treatment period which were also coded to that 
preferred term. Any AE present prior to the first dose of study drug that increases in intensity 
during the treatment period will be re-entered with a new start date of the date of increased 
intensity. 
Descriptive statistics (the number and percentage) for subjects reporting TEAEs in each 
treatment group will be tabulated by system organ class and preferred term; by system organ 
class, preferred term, and severity; and by system organ class, preferred term, and relationship to 
study drug. If more than 1 AE is coded to the same preferred term for the same subject, the 
subject will be counted only once for that preferred term using the most severe and most related 
occurrence for the summarization by severity and by relationship to the study drug. 
The by-frequency summaries will also include incidence of the SAEs and non-SAEs by preferred 
term that at least 2% of the subjects in one treatment group. Duration of AEs will be tabulated by 
treatment group. 
Fisher exact test will be used to compare EN3835 to placebo. 
Listings will be presented for subjects with SAEs, subjects with AEs leading to discontinuation 
of study or study drug, and subjects who die (if any). 
17.6.5. 
Vital Signs 
Descriptive statistics for vital signs (eg, systolic and diastolic blood pressure, pulse rate, and 
body weight) and their changes from baseline at each visit and at the end of study will be 
presented by treatment group. 
Vital sign values are potentially clinically important (PCI) if they meet both the observed value 
criteria and the change from baseline criteria. The criteria for PCI vital sign values will be 
detailed in the Statistical Analysis Plan (SAP). The PCI percentages will be calculated relative to 
the number of subjects with baseline and at least one post-baseline assessment. A supportive 
listing of subject values will be provided including the subject ID, study center, treatment group, 
baseline and post-baseline values. 
The change from baseline for vital signs parameters are compared between EN3835 and placebo 
using an analysis of variance (ANOVA) with a factor of drug (EN3835 or placebo) while Fisher 
exact test will be used for the incidence of PCI values. 
17.6.6. 
Clinical Laboratory Parameters 
Descriptive statistics for clinical laboratory values in International System of Units (SI units) and 
changes from baseline at Day 71 will be presented by treatment group for each clinical 
laboratory parameter. 

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The number and percentage of subjects with potentially clinically important (PCI) post-baseline 
clinical laboratory values will be tabulated by treatment group. The criteria for PCI laboratory 
values will be detailed in the Statistical Analysis Plan (SAP). The PCI percentages will be 
calculated relative to the number of subjects with at least one post-baseline assessment. A 
supportive listing of subjects with post-baseline PCI values will be provided, including the 
subject ID, study center, treatment group, baseline and post-baseline values. 
The change from baseline for clinical laboratory parameters are compared between EN3835 and 
placebo using an ANOVA with a factor of drug (EN3835 or placebo) while Fisher exact test will 
be used for the incidence of PCI values. 
17.6.7. 
Electrocardiogram 
Not applicable (ECG is done only at screening for the subject’s enrollment eligibility). 
17.6.8. 
Physical Examination 
Body weight and BMI at Day 22, Day 43, and Day 71 as well as their change from baseline 
(Day 1) at those time points will be presented by treatment group. 
17.6.9. 
Other Safety Measurements 
Not applicable. 
17.7. 
Pharmacokinetic Analyses 
Not applicable. 
17.8. 
Pharmacodynamic Analyses 
Not applicable. 
17.9. 
Other Data (eg, Health Economics/QOL, Pharmacogenetic, etc.) 
Not applicable. 
17.10. 
Interim Analysis 
No interim analysis is planned for this study. 
17.11. 
Statistical Software 
Statistical analyses will be performed using Version 9.3 (or higher) of SAS® (SAS Institute, 
Cary, NC). 
 

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18.5. 
Study Drug Accountability 
A drug inventory form must be kept current by the site staff designated to be responsible for 
reconstitution and must be made available to the clinical monitor, Endo employees, IRB/IEC, 
and regulatory agencies for routine inspection and accountability during monitoring visits. When 
instructed by Endo, the Investigator agrees to return all original used or unused study drug kits to 
Endo's return vendor. 
18.5.1. 
Study Drug Handling and Disposal 
The Investigator agrees not to supply study drug to any person except to those subjects enrolled 
in the study. The Investigator is responsible for recording the receipt and use of all drugs 
supplied and for ensuring the supervision of the storage and allocation of these supplies. All used 
and unused study drug will be returned, and unit counts will be performed whenever medication 
is returned. The site must account for all study drug received and its use. At the end of the study, 
all used and unused drug supplies will be returned to Endo’s return vendor. 
 

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19. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
19.1. 
Source Documents 
Source documents include but are not limited to original documents, data and records such as 
hospital/medical records (including electronic health records), clinic charts, lab results, subject 
diaries, data recorded in automated instruments, microfilm or magnetic media, and pharmacy 
records, etc. This study allows for direct data entry (DDE) for selected data points as outlined 
below: 
 PR-PCSS 
 CR-PCSS 
 S-GAIS 
 I-GAIS 
 PR-CIS 
 Subject Satisfaction with Cellulite Treatment Assessment 
All other data points, at a minimum, should have supporting source documentation for entries in 
the eCRF. 
19.2. 
Study Monitoring 
A representative of Endo Pharmaceuticals Inc. will meet with the Investigator and his/her staff 
prior to the entrance of the first subject to review study procedures and methods of recording 
findings in the eCRF. 
After enrollment of the first subject, an Endo Pharmaceuticals Inc. representative will be 
assigned to periodically monitor each Investigator site for study progress and to verify that 
standards of Good Clinical Practice (GCP) were followed. The Investigator is expected to 
prepare for the monitor visit, ensuring that all source documents, completed eCRFs, signed 
consent forms and other study related documents are readily available for review. 
19.3. 
Audits and Inspections 
The Investigator shall permit audits and inspections by the Sponsor, its representatives and 
members of regulatory agencies. The Investigator should immediately notify the Sponsor of an 
upcoming FDA or other regulatory agency inspection. 
19.4. 
Institutional Review Board (IRB) 
The Investigator shall permit members of the IRB/IEC to have direct access to source 
documents. 

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19.5. 
Data Recording and Documentation 
All data recordings and source documentation (including electronic health records) must be made 
available to the Sponsor (or designee), FDA and any other regulatory agencies that request 
access to study records, including source documents, for inspection and copying, in keeping with 
federal and local regulations. 
 

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20. 
QUALITY CONTROL AND QUALITY ASSURANCE 
Steps to assure the accuracy and reliability of data include the selection of qualified principal 
investigators and appropriate study centers, review of protocol procedures with the principal 
investigators and associated personnel prior to start of the study, and periodic monitoring visits 
conducted by the Sponsor or Sponsor representative. Significant and/or repeated non-compliance 
will be investigated and remedial action instituted when appropriate. Failure to comply with 
remedial actions may result in investigator site termination and regulatory authority notification. 
The Sponsor or its designee will utilize qualified monitors to review and evaluate activities 
conducted at Investigator Sites. 
The data will be entered into the clinical study database and verified for accuracy, following 
procedures defined by the Sponsor (or designee). Data will be processed and analyzed following 
procedures defined by the Sponsor (or designee). 
The study will be monitored and/or audited at intervals to ensure that the clinical study is 
conducted and data are generated, documented (recorded), and reported in compliance with the 
Study Protocol; International Conference on Harmonisation (ICH), E6 consolidated guidelines; 
and other applicable regulations. The extent, nature, and frequency of monitoring and/or audits 
will be based on such considerations as the study objectives and/or endpoints, the purpose of the 
study, study design complexity, and enrollment rate. At the conclusion of a program, a 
compliance statement will be generated by the Sponsor (or designee) listing all audit activities 
performed during the clinical study. 
 

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21. 
ETHICS 
21.1. 
Ethics Review 
Approval by the IRB/IEC prior to the start of the study will be the responsibility of the 
Investigator. A copy of approval documentation will be supplied to Endo Pharmaceuticals Inc. 
along with a roster of IRB members that demonstrates appropriate composition (a Department of 
Health and Human Services [DHHS] Assurance Number will satisfy this requirement). 
The study protocol, the informed consent form, advertisements, materials being provided to 
subjects and amendments (if any) will be approved to IRB/IECs at each study center in 
conformance with ICH E6, the Code of Federal Regulations (CFR), Title 21, Part 56 and any 
other applicable local laws. The Investigator is responsible for supplying the IRB/IEC with a 
copy of the current IB, Package Insert, or SPC as well as any updates issued during the study. 
During the course of the study, the Investigator will provide timely and accurate reports to the 
IRB/IEC on the progress of the study, at intervals not exceeding 1 year (or as appropriate), and 
will notify the IRB/IEC of SAEs or other significant safety findings, per the policy of the 
IRB/IEC. At the conclusion of the study, the Investigator will submit a final report or close out 
report to the IRB/IEC and provide a copy to Endo Pharmaceuticals Inc. 
Any amendment to this protocol will be provided to the Investigator in writing by Endo 
Pharmaceuticals Inc. No protocol amendment may be implemented (with the exceptions noted 
below) before it has been approved by the IRB and the signature page, signed by the 
Investigator, has been received by Endo Pharmaceuticals Inc. Where the protocol is amended to 
eliminate or reduce the risk to the subject, the amendment may be implemented before IRB 
review and approval. However, the IRB must be informed in writing of such an amendment and 
approval obtained within reasonable time limits. Deviating from the protocol is permitted only if 
absolutely necessary for the safety or clinical management of the subject, and must be 
immediately reported to Endo Pharmaceuticals Inc. 
The Investigator will be responsible for supplying updated safety and/or study information to 
study subjects as it becomes available. 
21.2. 
Ethical Conduct of the Study 
This clinical study is designed to comply with the ICH Guidance on General Considerations for 
Clinical Trials (62 FR 6611, December 17, 1997), Nonclinical Safety Studies for the Conduct of 
Human Clinical Trials for Pharmaceuticals (62 FR 62922, November 25, 1997), Good Clinical 
Practice: Consolidated Guidance (62 FR 25692, May 9, 1997) and 21 CFR parts 50, 54, 56,  
and 312. 
The study will be conducted in full compliance with ICH E6, the FDA guidelines for GCP and in 
accordance with the ethical principles that have their origins in the Declaration of Helsinki 
defined in 21 CFR, 312.120. 

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21.3. 
Subject Information and Consent 
Subjects, after having the study explained to them and an opportunity to have their questions 
answered sufficiently, will give voluntary and written informed consent (in compliance with ICH 
E6, 4.8 and 21 CFR Parts 50 and 312) before participating in any study-related procedures. The 
consent shall be written in a language understandable to the subject. Subjects unable to read 
(illiterate) shall have the consent process performed in the presence of an independent witness 
who shall also sign the consent. Each subject will read, assent understanding, and sign an 
instrument of informed consent after having had an opportunity to discuss the study and consent 
documents with the Investigator before signing, and will be made aware that she may withdraw 
from the study at any time. 
In addition to obtaining informed consent/assent, the Investigator is responsible for obtaining any 
additional documentation to demonstrate compliance with local privacy laws applicable to 
activities performed. 
The consent/assent process shall be recorded in source documents. Signed copies of the informed 
consent and/or assent will be given to the Subject/LAR and originals will be placed in the 
Investigator study files. 
A unique Subject identification number will be assigned according to section 12.1.2.2 at the time 
that the Subject signs the informed consent form. 
 

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22. 
DATA HANDLING AND RECORDKEEPING 
22.1. 
Data Collection 
Endo will provide an electronic data capture (EDC) system for this study. Data collection will 
involve the use of an EDC system to which only authorized personnel will have access. The 
system will be secured to prevent unauthorized access to the data or the system. This will include 
the requirement for a user ID and password to enter or change data. The level of access to the 
EDC system will be dependent on the person’s role in the study. 
Study data will be collected from source documents and entered into an eCRF within the EDC 
system. The Investigator will be responsible for ensuring the eCRFs are completed in a timely 
manner relative to the subject’s visit. In addition to periodic monitoring occurring within the 
system by a Sponsor monitor, programmatic edit checks will be used to review EDC data for 
completeness, logic, and adherence to the study protocol. As a result of this monitoring and these 
checks, queries may be issued electronically to the clinical study sites and closed electronically 
by the monitor, data management staff or authorized staff at the study site. Additionally, the 
Investigator will review eCRFs, ensure all missing or corrected data is provided and will sign the 
eCRF pages with an electronic signature. 
An electronic audit trail will be maintained in the EDC system to track all changes made to data 
entered in the eCRF. Data will be retrievable in such a fashion that all information regarding 
each individual subject is attributable to that subject. Unless otherwise indicated, all data 
captured in the eCRF must first be captured in source documents. Data that can be directly 
recorded in the eCRF will be clearly identified in the section(s) of the protocol that describes the 
assessment(s). 
Data entries will be corrected by changing the entry in the EDC system. Any changes or 
corrections to eCRF data will be electronically tracked and will include the reason for correction, 
who made the correction, and the date/time stamp when the correction was made within the audit 
trail of the EDC system. 
In addition, any contact with the subject via telephone or other means that provide significant 
clinical information must be documented in source documents as described above. 
22.2. 
Study Documentation 
Upon study completion, the Investigator will be provided with complete electronic copies of the 
case report form (CRF) data for his/her files. 

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23. 
REPORTING AND PUBLICATION 
All data generated in this study are the property of Endo Pharmaceuticals Inc. An integrated 
clinical and statistical report will be prepared at the completion of the study. 
Publication of the results by the Investigator will be subject to mutual agreement between the 
Investigator and Endo Pharmaceuticals Inc. 
 

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24. 
INVESTIGATOR OBLIGATIONS 
24.1. 
Regulatory Documents 
The Investigator is responsible for creating and/or maintaining all study documentation required 
by 21CFR 50, 54, 56 and 312, ICH, E6 section 8, as well as any other documentation defined in 
the protocol or the Investigator Agreement. The Investigator must maintain the documentation 
relating to this study and permit Endo Pharmaceuticals Inc. or a member of a regulatory agency 
access to such records. 
The Investigator must provide the following key documents to Endo Pharmaceuticals Inc. prior 
to the start of the study: 
 A completed and signed Form FDA 1572. If during the course of the study any 
information reported on the Form FDA 1572 changes, a revised Form FDA 1572 
must be completed and returned to Endo Pharmaceuticals Inc. for submission to the 
FDA. For studies executed outside the United States, documentation required by the 
governing regulatory authority may be substituted for the Form FDA 1572. 
 A fully executed contract 
 The Investigator’s Statement page in this protocol signed and dated by the 
Investigator and any subsequent amendment signature pages 
 The IB acknowledgment of receipt page 
 Curricula vitae for the Principal Investigator and all sub-Investigators listed on Form 
FDA 1572, including a copy of each physician’s license (if applicable) 
 A copy of the original IRB/IEC approval for conducting the study. If the study is 
ongoing, renewals must be submitted at yearly intervals or shorter intervals defined 
by the IRB/IEC. All subsequent modifications must be submitted and approved by the 
IRB, as described in section 21.1 
 A copy of the IRB/IEC-approved informed consent form 
 A list of IRB/IEC members or DHHS Assurance Number 
 Laboratory certifications and normal ranges (if local labs are required by the protocol) 
 A financial disclosure agreement completed and signed by the Investigator and all 
sub-Investigators listed on Form FDA 1572. Investigator site staff that submitted an 
initial financial disclosure are also responsible for informing Endo Pharmaceuticals 
Inc. of any changes to their initial financial disclosure form 1 year after the 
completion of the study 
A complete list of required regulatory documents will be supplied by Endo Pharmaceuticals Inc. 
or its representative. 

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24.2. 
Delegation of Responsibilities and Adequate Resources 
The Investigator should have adequate time to conduct the study properly and should have an 
adequate number of qualified staff to assist with the conduct of the study. The Investigator shall 
delegate tasks only to individuals qualified by education, training and experience to perform the 
delegated tasks. The Investigator shall have direct oversight of all delegated activities and shall 
document delegation of responsibilities. The Investigator is responsible for ensuring all delegated 
staff have been properly trained on the protocol and their assigned study responsibilities. 
24.3. 
Medical Care of Study Subjects 
The Investigator and/or a qualified sub-Investigator shall be responsible for the subjects’ medical 
care. Any unrelated medical condition discovered during the course of the study should be 
communicated to the subject so that they may seek appropriate medical care. The Investigator 
will report all AEs as required by the protocol (section 14.5). The Investigator will inform study 
subjects of new information regarding the study drug as it becomes available. 
24.4. 
Use of Investigational Materials 
The Investigator will acknowledge that the study drug supplies are investigational and as such 
must be used strictly in accordance with the protocol and only under the supervision of the 
Principal Investigator or sub-Investigators listed on Form FDA 1572 (or other regulatory 
document, depending on region). Study drug must be stored in a safe and secure location. At 
study initiation, a representative from Endo Pharmaceuticals Inc. will inventory the study drug at 
the site. The Investigator must maintain adequate records documenting the receipt and 
disposition of all study supplies. Endo Pharmaceuticals Inc. or its representative will supply 
forms to document total inventory as well as subject specific accountability. The Investigator is 
responsible for monitoring subject’s use of the study drug to ensure compliance with the 
protocol. All study supplies shall be returned to Endo Pharmaceuticals Inc. or its designee. 
24.5. 
Retention of Records 
Federal and local regulations require that the Investigator retain a copy of all regulatory 
documents and records that support the data for this study (eg, informed consents, laboratory 
reports, source documents, study drug dispensing records) for whichever of the following is the 
longest period of time: 
 A period of 2 years following the final date of approval by the FDA or other 
regulatory agency of the study drug for the purposes that were the subject of the 
investigation; or 
 A period of 5 years following the date on which the results of the investigation were 
submitted to the FDA or other regulatory agency in support of, or as part of, an 
application for a research or marketing permit for the study drug for the purposes that 
were the subject of the investigation 
Endo Pharmaceuticals Inc. will notify Investigators once one of the above 2 timeframes has been 
satisfied. 

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If the investigation does not result in the submission of the data in support of, or as part of, an 
application for a research or marketing permit, records must be retained for a period of 2 years 
following notification by Endo Pharmaceuticals Inc. that the entire clinical investigation (not 
merely the Investigator’s portion) is completed, terminated, or discontinued or 2 years following 
withdrawal of the Investigational New Drug application (IND)/Clinical Trial Authorization 
(CTA) or request for marketing approval (New Drew Application [NDA]/Marketing 
Authorization Application [MAA]). 
If the Investigator retires, relocates, or for other reasons withdraws from the responsibility of 
keeping the study records, custody must be transferred to a person who will accept the 
responsibility. Endo Pharmaceuticals Inc. must be notified in writing of the name and address of 
the new custodian. Study records should not be destroyed without consultation with Endo 
Pharmaceuticals Inc. 
24.6. 
Subject Confidentiality 
All subject records submitted to Endo Pharmaceuticals Inc. or its designee will be identified only 
by initials and subject number. Subjects’ names are not to be transmitted to Endo 
Pharmaceuticals Inc. The Investigator will keep a Master Subject List on which the identification 
number and the full name, address, and telephone number of each subject are listed. It is the 
Investigators’ responsibility to inform study subjects that representatives of the Sponsor, FDA, or 
other regulatory agencies may review all records that support their participation in the study. The 
Investigator will adhere to all privacy laws to which he/she is subject. 
 

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25. 
TERMINATION OF STUDY 
The Sponsor has the right to suspend or terminate the study at any time. The study may be 
suspended or terminated for any reason. 
 

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26. 
INVESTIGATOR’S STATEMENT 
I agree to conduct the study in accordance with the protocol, and with all applicable government 
regulations and Good Clinical Practice guidance. 
 
 
 
_____/_____/______ 
Investigator’s Signature 
Date 
 
 
 
Typed Name of Investigator 
 

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27. 
REFERENCES 
1. Khan MH, Victor F, Rao B, Sadick NS. Treatment of cellulite: Part I. Pathophysiology. 
J Am Acad Dermatol 2010;62(3):361-70. 
2. Hexsel D, de Oliveira Dal’Forno T, Mazzuco R. Definition, clinical aspects, 
classifications, and diagnostic techniques. In: Goldman MP, Hexsel D, eds. Cellulite: 
Pathophysiology and Treatment. 2nd ed. New York, NY: Informa Healthcare; 
2010:13-21. 
3. Rawlings AV. Cellulite and its treatment. Int J Cosmetic Sci. 2006;28(3):175-90. 
4. Terranova F, Berardesca E, Maibach H. Cellulite: nature and aetiopathogenesis. Int J 
Cosmetic Sci. 2006;28(3):157-67. 
5. Avram MM. Cellulite: a review of its physiology and treatment. J Cosmet Laser Ther. 
2004;6(4):181-5. 
6. Khan MH, Victor F, Rao B, Sadick NS. Treatment of cellulite: Part II. Advances and 
controversies. J Am Acad Dermatol 2010;62(3):373-84. 
7. Collis N, Elliot LA, Sharpe C, Sharpe DT. Cellulite treatment: a myth or reality: a 
prospective randomized, controlled trial of two therapies, endermologie and 
aminophylline cream. Plast Reconstr Surg. 1999;104(4):1110-4. 
8. Hexsel DM, Mazzuco R. Subcision: a treatment for cellulite. Int J Dermatol. 
2000;39(7):539-44. 
9. Boyce S, Pabby A, Chuchaltkaren P, Brazzini B, Goldman MP. Clinical evaluation of a 
device for the treatment of cellulite: Triactive. Am J Cosmet Surg. 2005;22:233-7. 
10. DiBernardo BE. Treatment of cellulite using a 1440-nm pulsed laser with one-year 
follow-up. Aesthet Surg J. 2011;31(3):328-41. 
11. Investigational Brochure: Collagenase Clostridium Histolyticum for Injection 
(AA4500/EN3835), Version 7.0. Endo Pharmaceuticals Inc.; May 2016. 
 

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APPENDIX A. DOCUMENTS REQUIRED PRIOR TO INITIATION OF 
THE STUDY 
As a sponsor of a clinical study, Endo Pharmaceuticals Inc. has an obligation to ensure that the 
study will be conducted by a qualified Investigator with sufficient resources of time, personnel, 
and physical facilities to conduct the study and to ensure that the Investigator understands and 
agrees to comply with the protocol, applicable regulations, policies, and procedures. The 
following documentation is required: 
From the Principal Investigator 
1. A signed agreement to perform the study per protocol (the signature page will suffice). 
2. A signed Letter of Financial Agreement (including confidentiality statement). 
3. Name(s) of the Principal Investigator and of all sub-Investigator(s) 
4. All address(es) of the clinical site(s). 
5. A current medical license valid where he/she practices and a current curriculum vitae for 
the Principal Investigator (signed and dated) and all sub-Investigators, to contain at least 
the following elements: 
a. For physicians: 
i. Date of degree in Medicine 
ii. Name of the Institution granting the degree in Medicine 
iii. Previous clinical postings with dates 
b. For non-physician allowed by national law or regulations to act as clinical 
Investigators: 
i. Date and description of most advanced degree 
ii. Name of the Institution granting the degree in number (i) 
iii. Other accreditation or qualifications relevant to the study 
iv. Previous postings with dates 
v. Name and qualification (see 5a above) of the physician or dentist in charge of 
study subjects 
Note: If a non-physician is serving as Principal Investigator, then a qualified physician 
must be assigned as a sub-Investigator for the trial, to be responsible for all trial-related 
medical decisions. 
6. Written notification of Institutional Review Board/Independent Ethics Committee/Human 
Research Ethics Committee (IRB/IEC/HREC) approval. The minimum requirements are 
as follows: 
a. Dated letter, including: 
i. The date on which the meeting for the review of the study protocol took place 
ii. Study protocol/amendment number, and version date 

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iii. A clear statement of approval of the protocol and the informed consent text with 
version date, and authorization for the study to proceed 
iv. If the Investigator or any sub-Investigator is a part of the IRB/IEC/HREC 
Review Board, assurance that the Investigator abstained from voting at the 
meeting(s) when the study was discussed. 
b. A dated list of the members and their occupations 
c. A specimen copy of the Committee-approved informed consent text to be used in the 
study 
7. Food and Drug Administration (FDA) Form 1572 (for studies submitted under a US 
Investigational New Drug application [IND]). 
8. Financial Disclosure Certification or Certification of Non-Disclosure (for studies to be 
submitted for a US New Drug Application/Biologics License Application [NDA/BLA]). 
Other 
Any other documentation required by national law or regulations to be in the possession of the 
sponsor or the Investigator for study participation or study initiation. 

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APPENDIX B. PATIENT-REPORTED PHOTONUMERIC CELLULITE SEVERITY SCALE (PR-PCSS) 
FOR THE BUTTOCK 
 
 

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APPENDIX C. CLINICIAN-REPORTED PHOTONUMERIC CELLULITE SEVERITY SCALE 
(CR-PCSS) FOR THE BUTTOCK 
 

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APPENDIX D. PATIENT REPORTED CELLULITE IMPACT SCALE 
(PR-CIS) 
Please select the rating that best represents your answer on a scale of 0 to 10 with 0 representing 
“Not at all” and 10 representing “Extremely” while viewing digital images of your buttocks. 
Please answer each question. 
1. Thinking about the areas selected for treatment, how happy are you with the appearance of 
your cellulite? 
Not at all 
 
 
 
 
 
 
 
 
 
Extremely 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
2. Thinking about the areas selected for treatment, how bothered are you by the appearance of 
your cellulite? 
Not at all 
 
 
 
 
 
 
 
 
 
Extremely 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
3. Thinking about the areas selected for treatment, how self-conscious are you about the 
appearance of your cellulite? 
Not at all 
 
 
 
 
 
 
 
 
 
Extremely 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
4. Thinking about the areas selected for treatment, how embarrassed are you about the 
appearance of your cellulite? 
Not at all 
 
 
 
 
 
 
 
 
 
Extremely 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
5. Thinking about the areas selected for treatment, how much older do you look because of your 
cellulite? 
Not at all 
 
 
 
 
 
 
 
 
 
Extremely 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
6. Thinking about the areas selected for treatment, how overweight or out of shape do you look 
because of your cellulite? 
Not at all 
 
 
 
 
 
 
 
 
 
Extremely 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 

Protocol 
 
 
 
 
Endo Pharmaceuticals Inc. 
1400 Atwater Drive 
Malvern, PA 19355 USA 
 
EN3835 
EN3835-303 
A PHASE 3, RANDOMIZED, DOUBLE-BLIND, 
PLACEBO-CONTROLLED STUDY OF EN3835 IN THE 
TREATMENT OF EDEMATOUS FIBROSCLEROTIC 
PANNICULOPATHY 
IND 110077 
 
 
Date: 
September 27, 2017 
 
 
Auxilium Pharmaceuticals, Inc. (Auxilium) was acquired by Endo International plc. in 
January 2015. The sponsor of the application remains as Auxilium Pharmaceuticals, LLC, 
1400 Atwater Drive, Malvern, PA; however, Endo Pharmaceuticals Inc. is authorized to act and 
to communicate on behalf of Auxilium. 
 
 
 
Confidentiality Statement 
 
 

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2. 
SUMMARY OF CHANGES 
Not applicable. 

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4. 
SYNOPSIS 
Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
Title of Study: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of EN3835 in the 
Treatment of Edematous Fibrosclerotic Panniculopathy 
Lead Principal Investigator: 
Study Period:  
Estimated date first subject enrolled:  
Jan-2018 
Estimated date last subject completed:  
Sep-2018 
Phase of Development: 3 
Objectives:  
To assess the efficacy and safety of EN3835 in the treatment of edematous fibrosclerotic panniculopathy 
(EFP), commonly known as cellulite, in adult women  
Study Design: This study is a Phase 3 randomized, double-blind, placebo-controlled study of the 
efficacy and safety of EN3835 in the treatment of EFP in adult women. Subjects will be screened for 
study eligibility within 14 days prior to enrolling in this study. Subjects with 2 treatment areas (bilateral 
buttocks) (also referred to as quadrants) with moderate or severe levels of cellulite as independently 
assessed by the subject using the Patient Reported Photonumeric Cellulite Severity Scale (PR-PCSS) 
and by the Investigator using the Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 
and a Hexsel Cellulite Severity Scale no greater than 13 will be eligible. The eligibility of the buttocks 
will be confirmed on Day 1. 
Once the eligibility of the buttocks is confirmed, subjects will be randomly assigned to a treatment 
group (EN3835 0.84 mg per buttock or placebo) in a 1:1 ratio within an investigational site. Each 
subject will receive a treatment course which consists of up to 3 treatment visits (sessions), separated by 
21 days (ie, Days 1, 22, and 43). Each treatment visit will consist of 12 injections (0.3 mL per injection 
of EN3835 0.07 mg/injection or placebo; 0.84 mg in 3.6 mL per buttock) in each of the two buttocks for 
a total volume of 7.2 mL (1.68 mg). Selection of dimples to be treated in the buttocks will be at the 
discretion of the Investigator. End of study will occur at study day 71.  
At each treatment visit, each of the buttocks will be photographed before and after marking dimples and 
injection sites while the subject is in a consistent, standardized relaxed standing pose. The subject will 
assess the digital photographic image (pre-marking) of each of the buttocks using the PR-PCSS to 
determine the severity of EFP in each of the buttocks. In addition, the subject will evaluate each of the 
buttocks using a Subject Global Aesthetic Improvement Scale (S-GAIS). Subsequently, the Investigator 
will conduct live assessments of each buttock using the CR-PCSS. The subject assessments will always 
be completed prior to and independently of the Investigator assessments at each treatment visit. In 
addition, the Investigator will assess each of the buttocks using an Investigator Global Aesthetic 
Improvement Scale (I-GAIS). All of the assessments must be done before the dimple marking. 
At Day 71 (End of Study/Early Termination), photographs of each of the buttocks will be taken and 
evaluated by subject using the PR-PCSS. The Investigator will conduct live assessments of each of the 
buttocks using the CR-PCSS. Global assessment evaluations will be completed by both the subject and 
the Investigator. 
Number of Subjects (Planned): 420 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
Study Center(s): Approximately 25 sites in United States 
Diagnosis and Inclusion/Exclusion Criteria: 
Inclusion Criteria: 
1. Voluntarily sign and date an informed consent agreement 
2. Be a female ≥18 years of age 
3. At Screening visit, have 2 bilateral buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as reported by the Investigator (CR-PCSS), and 
c. a Hexsel CSS score no greater than 13 
4. At Day 1 visit, have 2 bilateral buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as reported by the Investigator (CR-PCSS), and 
c. a Hexsel CSS score no greater than 13 
5. Be willing to apply sunscreen to the buttocks before each exposure to the sun while participating 
in the study (ie, Screening through end of study) 
6. Be judged to be in good health, based upon the results of a medical history, physical 
examination, and laboratory profile at Screening  
7. Have a negative serum pregnancy test at Screening and a negative urine pregnancy test before 
injection of study drug and be using a stable and effective contraception method (eg, abstinence, 
intrauterine device [IUD], hormonal [estrogen/progestin] contraceptives, or double barrier 
method) for at least 1 menstrual cycle prior to study enrollment and for the duration of the 
study; or be menopausal defined as 12 months of amenorrhea in the absence of other biological 
or physiological causes, as determined by the Investigator; or post-menopausal for at least 
1 year; or be surgically sterile  
8. Be willing and able to cooperate with the requirements of the study 
9. Be able to read, complete and understand the patient-reported outcomes rating instruments in 
English 
Exclusion Criteria: 
A subject will be excluded from study participation if she: 
1. Has any of the following systemic conditions: 
a. Coagulation disorder 
b. Evidence or history of malignancy (other than excised basal-cell carcinoma) unless there 
has been no recurrence in at least 5 years 
c. History of keloidal scarring or abnormal wound healing 
d. Concurrent diseases or conditions that might interfere with the conduct of the study, 
confound the interpretation of the study results, or endanger the subject’s well-being. Any 
questions about concurrent diseases should be discussed with the Medical Monitor 
e. Evidence of clinically significant abnormalities on physical examination, vital signs, 
electrocardiogram (ECG), or clinical laboratory values 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
2. Has any of the following local conditions in the areas to be treated: 
a. History of lower extremity thrombosis or post-thrombosis syndrome 
b. Vascular disorder (eg, varicose veins, telangiectasia) in area to be treated 
c. Inflammation or active infection  
d. Active cutaneous alteration including rash, eczema, psoriasis, or skin cancer 
e. Has a tattoo and/or a mole located within 2 cm of the site of injection  
3. Requires the following concomitant medications before or during participation in the trial: 
a. Anticoagulant or antiplatelet medication or has received anticoagulant or antiplatelet 
medication (except for ≤150 mg aspirin daily) within 7 days before injection of study drug 
4. Has used any of the following for the treatment of EFP on a buttock within the timelines 
identified below or intends to use any of the following at any time during the course of the 
study: 
a. Liposuction in a buttock during the 12-month period before injection of study drug 
b. Injections (eg, mesotherapy); radiofrequency device treatments; laser treatment; buttock 
implant treatment; cryolipolysis; or surgery (including subcision and/or powered subcision) 
within a buttock during the 12-month period before injection of study drug 
c. Any investigational treatment for EFP on a buttock during the 12-month period before 
injection of study drug 
d. Endermologie™ or similar treatments within a buttock during the 6-month period before 
injection of study drug 
e. Massage therapy within a buttock during the 3-month period before injection of study drug 
f. Creams (eg, Celluvera™, TriLastin®) and/or home therapies to prevent or mitigate EFP 
within a buttock during the 2-week period before injection of study drug 
5. Is presently nursing or providing breast milk 
6. Intends to become pregnant during the study 
7. Intends to initiate an intensive sport or exercise program during the study 
8. Intends to initiate a weight reduction program during the study 
9. Intends to use tanning spray or tanning booths during the study 
10. Has received an investigational drug or treatment within 30 days before injection of study drug 
11. Has a known systemic allergy to collagenase or any other excipient of study drug 
12. Has received any collagenase treatments at any time prior to treatment 
13. Was a subject in a previous cellulite clinical trial of collagenase clostridium histolyticum 
(CCH): AUX-CC-830, AUX-CC-831, EN3835-102, EN3835-104, EN3835-201, and/or 
EN3835-202 
14. Any other condition(s) that, in the Investigator’s opinion, might indicate the subject to be 
unsuitable for the study 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
Investigational Product, Dosage and Mode of Administration: EN3835, 1.68 mg, subcutaneous. A 
dose of 0.84 mg of EN3835 per buttock will be administered as 12 subcutaneous injections (0.3-mL 
injection administered as three 0.1-mL aliquots per injection) in each of two buttocks for a total dose of 
1.68 mg and a total volume of 7.2 mL (3.6 mL per buttock). Total number of injections will be 
24 injections per treatment visit into the two buttocks. There will be 3 treatment visits at 21 days 
intervals, ie, treatments on Days 1, 22, and 43 will be administered. 
Duration of Study: Approximately 84 days (includes screening phase) 
Screening Phase: Up to 14 days 
Criteria for Evaluation: 
Efficacy: 
 
Subject using PR-PCSS while viewing digital image of the left buttock: 5-level scale 
ranging from 0 (no cellulite) to 4 (severe cellulite) (Day 1 (Baseline) and Days 22, 43, and 
71) for the left buttock 
 
Subject using PR-PCSS while viewing digital image of the right buttock: 5-level scale 
ranging from 0 (no cellulite) to 4 (severe cellulite) (Day 1 (Baseline) and Days 22, 43, and 
71) for the right buttock 
 
Investigator using the CR-PCSS by live assessment: 5-level scale ranging from 0 (no 
cellulite) to 4 (severe cellulite) (Day 1 (Baseline) and Days 22, 43, and 71) for the left 
buttock 
 
Investigator using the CR-PCSS by live assessment: 5-level scale ranging from 0 (no 
cellulite) to 4 (severe cellulite) (Day 1 (Baseline) and Days 22, 43, and 71) for the right 
buttock 
 
Investigator Global Aesthetic Improvement Scale (I-GAIS): 7-level scale ranging from 3 
(very much improved) to −3 (very much worse) (Days 22, 43, and 71) for the left buttock 
 
Investigator Global Aesthetic Improvement Scale (I-GAIS): 7-level scale ranging from 3 
(very much improved) to −3 (very much worse) (Days 22, 43, and 71) for the right buttock 
 
Subject Global Aesthetic Improvement Scale (S-GAIS): 7-level scale ranging from 3 (very 
much improved) to −3 (very much worse) (Days 22, 43, and 71) for the left buttock 
 
Subject Global Aesthetic Improvement Scale (S-GAIS): 7-level scale ranging from 3 (very 
much improved) to −3 (very much worse) (Days 22, 43, and 71) for the right buttock 
 
Subject satisfaction with cellulite treatment assessment: 5-level scale ranging from 2 (very 
satisfied) to −2 (very dissatisfied) (Day 71) for both left and right buttocks 
Safety: 
Safety will be assessed throughout the study through the recording of: 
 
Adverse events (AEs) (including those of special interest (AESI); which are adverse events 
such as bruising, ecchymosis, hematomas, and contusions that occur remote to the site of 
drug administration, or any hypersensitivity reactions, including anaphylaxis) 
 
Vital signs 
 
Clinical laboratory tests 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
Analyses:  
Analyses of Primary Endpoint: 
The primary endpoint is the proportion of 2-level composite responders at Day 71 defined as subjects 
with at least one of two treated buttocks with: 
 
an improvement in severity from baseline (Day 1 visit) of at least 2 levels of severity in the 
CR-PCSS as assessed live by the Investigator, and 
 
an improvement in severity from baseline of at least 2 levels of severity in the PR-PCSS as 
assessed by the subject while viewing the digital image of the same buttock. 
A subject will be considered a responder if these criteria are met in the left buttock or right buttock or 
both buttocks in that subject. 
The primary endpoint will be summarized as percentages and analyzed using a Cochran-Mantel-
Haenszel test that compares the 2 treatment groups and adjusts for Investigator at a level of significance 
of 0.05. The ITT population will be evaluated for the primary endpoint with any subject not having an 
evaluation of CR-PCSS and/or PR-PCSS at Day 71 classified as a non-responder. 
Sensitivity analyses for the primary endpoint will include: 
 
ITT subjects with missing data handled by multiple imputation (MI) approach 
 
ITT subjects with missing data handled by a last observation carried forward (LOCF) 
approach 
 
mITT subjects with missing data handled by an LOCF approach 
 
Observed data only (no missing data imputed) 
 
Per-protocol (PP) subjects with missing data handled by an LOCF approach if 10% or more 
subjects are excluded in the PP population from mITT population. 
Analyses of Key Secondary Endpoints:  
There will be 4 key secondary endpoints grouped as two families of 2 endpoints per family analyzed in a 
hierarchical order. 
 
Family #1 – two endpoints: 
- 
Proportion of 1-level PR-PCSS responders defined as subjects with ≥1-level 
improvement in PR-PCSS severity rating of left buttock at Day 71 compared to Day 1 
- 
Proportion of 1-level PR-PCSS responders defined as subjects with ≥1-level 
improvement in PR-PCSS severity rating of right buttock at Day 71 compared to Day 1 
 
Family #2 – two endpoints: 
- 
Proportion of 1-level S-GAIS responders defined as subjects with ≥1-level 
improvement (improved, much improved or very much improved) in the S-GAIS 
assessment of left buttock at Day 71 
- 
Proportion of 1-level S-GAIS responders defined as subjects with ≥1-level 
improvement (improved, much improved or very much improved) in the S-GAIS 
assessment of right buttock at Day 71 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
The key secondary efficacy analyses will be analyzed in the same manner as the primary endpoint based 
on the ITT population. The family #1 key secondary efficacy analyses will be performed only if the 
primary efficacy analysis is significant at a significance level of p ≤ 0.05 (gatekeeping strategy). 
Similarly, family #2 key secondary efficacy analyses will be performed only if at least one of the key 
secondary efficacy endpoints of family #1 is significant at a significance level of p ≤ 0.025 (parallel 
gatekeeping strategy). Within a family of key secondary efficacy endpoints, Bonferroni method will be 
performed to relocate unused alpha for testing each endpoint to assure an overall error rate of p ≤ 0.05. 
The details of the testing procedures will be provided in the statistical analysis plan for the study. 
Supportive Endpoints: 
The supportive variables will evaluate assessments at various study time points and using various 
populations.  
 
Proportion of 2-level PR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 2 levels of severity in the PR-PCSS) of the left buttock 
(Days 22, 43, and 71) 
 
Proportion of 2-level PR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 2 levels of severity in the PR-PCSS) of the right buttock 
(Days 22, 43, and 71) 
 
Proportion of 1-level PR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 1 level of severity in the PR-PCSS) of the left buttock 
(Days 22, 43, and 71) 
 
Proportion of 1-level PR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 1 level of severity in the PR-PCSS) of the right buttock 
(Days 22, 43, and 71) 
 
Proportion of 2-level PR-PCSS responders of at least one buttock (Days 22, 43, and 71). A 
subject will be considered a responder if this criterion is met in the left buttock or right 
buttock or both buttocks in that subject. 
 
Proportion of 1-level PR-PCSS responders of at least one buttock (Days 22, 43, and 71). A 
subject will be considered a responder if this criterion is met in the left buttock or right 
buttock or both buttocks in that subject.  
 
Proportion of 2-level PR-PCSS responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both left and 
right buttocks. 
 
Proportion of 1-level PR-PCSS responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both left and 
right buttocks. 
 
Proportion of 2-level CR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 2 levels of severity in the CR-PCSS) of the left buttock 
(Days 22, 43, and 71)  
 
Proportion of 2-level CR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 2 levels of severity in the CR-PCSS) of the right buttock 
(Days 22, 43, and 71) 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
 
Proportion of 1-level CR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 1 level of severity in the CR-PCSS) of the left buttock 
(Days 22, 43, and 71) 
 
Proportion of 1-level CR-PCSS responders (defined as subjects with an improvement in 
severity from baseline of at least 1 level of severity in the CR-PCSS) of the right buttock 
(Days 22, 43, and 71) 
 
Proportion of 2-level CR-PCSS responders of at least one buttock (Days 22, 43, and 71). A 
subject will be considered a responder if this criterion is met in the left buttock or right 
buttock or both buttocks in that subject 
 
Proportion of 1-level CR-PCSS responders of at least one buttock (Days 22, 43, and 71). A 
subject will be considered a responder if this criterion is met in the left buttock or right 
buttock or both buttocks in that subject 
 
Proportion of 2-level CR-PCSS responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both left and 
right buttocks 
 
Proportion of 1-level CR-PCSS responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both left and 
right buttocks 
 
Proportion of 1-level composite responders of the left buttock (defined as subjects with an 
improvement in severity from baseline of at least 1 level of severity in the CR-PCSS of the 
left buttock assessed live by the Investigator and an improvement of severity from baseline 
of at least 1 level of severity in the PR-PCSS of that same left buttock) (Days 22, 43, 
and 71) 
 
Proportion of 1-level composite responders of the right buttock (defined as subjects with an 
improvement in severity from baseline of at least 1 level of severity in the CR-PCSS of the 
right buttock assessed live by the Investigator and an improvement of severity from baseline 
of at least 1 level of severity in the PR-PCSS of that same right buttock) (Days 22, 43, 
and 71) 
 
Proportion of 1-level composite responders of at least one buttock (Days 22, 43, and 71). A 
subject will be considered a responder if this criterion is met in the left buttock or right 
buttock or both buttocks in that subject. 
 
Proportion of 1-level composite responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both left and 
right buttocks. 
 
Proportion of 2-level composite responders of the left buttock (defined as subjects with an 
improvement in severity from baseline of at least 2 levels of severity in the CR-PCSS of the 
left buttock assessed live by the Investigator and an improvement of severity from baseline 
of at least 2 levels of severity in the PR-PCSS of that same left buttock) (Days 22, 43, 
and 71) 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
 
Proportion of 2-level composite responders of the right buttock (defined as subjects with an 
improvement in severity from baseline of at least 2 levels of severity in the CR-PCSS of the 
right buttock assessed live by the Investigator and an improvement of severity from baseline 
of at least 2 levels of severity in the PR-PCSS of that same right buttock) (Days 22, 43, 
and 71) 
 
Proportion of 2-level composite responders of at least one of two buttocks (Days 22, 43, 
and 71). A subject will be considered a responder if this criterion is met in the left buttock 
or right buttock or both buttocks in that subject.  
 
Proportion of 2-level composite responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both left and 
right buttocks. 
 
Proportion of subjects at each level of the S-GAIS of the left buttock (Days 22, 43, and 71) 
 
Proportion of subjects at each level of the S-GAIS of the right buttock (Days 22, 43, and 71) 
 
Proportion of 1-level S-GAIS responders defined as subjects with a response of at least 1 
(improved) in the S- GAIS of the left buttock (Days 22, 43, and 71) 
 
Proportion of 1-level S-GAIS responders defined as subjects with a response of at least 1 
(improved) in the S- GAIS of the right buttock (Days 22, 43, and 71) 
 
Proportion 1-level S-GAIS responders of at least one buttock (Days 22, 43, and 71). A 
subject will be considered a responder if this criterion is met in the left buttock or right 
buttock or both buttocks in that subject. 
 
Proportion of 1-level S-GAIS responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both left and 
right buttocks. 
 
Proportion of subjects at each level of the I-GAIS of the left buttock (Days 22, 43, and 71) 
 
Proportion of subjects at each level of the I-GAIS of the right buttock (Days 22, 43, and 71) 
 
Proportion of 1-level I-GAIS responders (defined as subjects with a response of at least 1 
(improved) in the Investigator GAIS assessment) of at least one buttock (Days 22, 43, 
and 71). A subject will be considered a responder if this criterion is met in the left buttock 
or right buttock or both buttocks in that subject.  
 
Proportion of 1-level I-GAIS responders of two buttocks in the same individual (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in both left and 
right buttocks. 
 
Proportion of subjects at each level of the subject satisfaction with cellulite treatment 
(Day 71) 
 
Proportion of satisfied responders (defined as subjects with a response of at least 1 
(ie, 1-Satisfied or 2-Very Satisfied) in the subject satisfaction with cellulite treatment 
assessment (Day 71) 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
All supportive endpoints will be summarized as percentages. The dichotomous secondary endpoints 
(ie, responder endpoints) will be analyzed using a Cochran-Mantel-Haenszel test adjusted for 
Investigator. Changes in the PR-PCSS ratings and CR-PCSS ratings from baselines, S-GAIS scores, and 
I-GAIS scores will be analyzed using the Mann-Whitney test. 
Safety Analysis: 
The following variables are safety endpoints: 
 
AEs: Mapped to preferred term using the Medical Dictionary for Regulatory Activities 
(MedDRA) 
 
Vital signs 
 
Clinical laboratory tests 
AEs will be summarized by proportion of subjects reporting each event. Fisher exact test will be used to 
compare EN3835 to placebo. Descriptive statistics will be presented for actual and change from baseline 
at each visit for vital signs and for each clinical laboratory test parameter. The comparison between 
treatment groups will be based on the change from baseline for clinical laboratory tests and vital signs 
using an analysis of variance (ANOVA) with a factor of drug (EN3835 or placebo). 
Immunogenicity: Anti-AUX-I and anti-AUX-II antibody levels will be summarized using descriptive 
statistics for the actual value at the visit. Samples from Day 1, Day 22, Day 43, and Day 71 visits will be 
analyzed for anti-AUX-I and anti-AUX-II antibodies and a subset of Day 1 and Day 71 samples will be 
analyzed for neutralizing antibodies. 

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5. 
SCHEDULE OF EVENTS 
Procedures 
Day -14 to -1 
 
Screening 
Day 1 
Treatment  
Visit 1 
Day 22 (± 3 d) 
Treatment  
Visit 2 
Day 43 (± 3 d) 
Treatment  
Visit 3 
Day 71 (+ 5 d) / 
End of Study / 
Early Termination 
Unscheduled 
Clinic Visita 
Informed consent 
X 
 
 
 
 
 
Inclusion/exclusion 
X 
 
 
 
 
 
Digital photography 
X 
Xb 
Xb 
Xb 
X 
X 
Medical history/EFP history including previous 
treatments 
X 
 
 
 
 
 
Prior/concomitant medications/procedures 
X 
X 
X 
X 
X 
X 
Physical examination: 
X 
 
 
 
X 
 
 Body weight 
X 
 
Xc 
Xc 
X 
X 
 Height  
X 
 
 
 
 
 
 Fitzpatrick skin type 
X 
 
 
 
 
 
Vital signs 
X 
Xd 
Xd 
Xd 
X 
X 
12-lead ECG 
X 
 
 
 
 
 
Collection of samples: 
 Clinical laboratory 
X 
 
 
 
X 
X 
 Anti-AUX-I/anti-AUX-II antibody level 
 
Xc 
Xc 
Xc 
X 
 
 Pregnancy testing 
Xe 
Xc,e 
Xc,e 
Xc,e 
Xe 
X 
Subject cellulite assessmentsf: 
 Patient Reported Photonumeric Cellulite 
Severity Scale (PR-PCSS) 
Xg,h 
Xc,g,h 
Xc,g,h 
Xc,g,h 
Xg,h 
 
 Subject Global Aesthetic Improvement 
(S-GAIS) 
 
 
Xc,g,h 
Xc,g,h 
Xg,h 
 
 Subject Satisfaction With Cellulite Treatment 
Assessment 
 
 
 
 
Xg 
 

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Procedures 
Day -14 to -1 
 
Screening 
Day 1 
Treatment  
Visit 1 
Day 22 (± 3 d) 
Treatment  
Visit 2 
Day 43 (± 3 d) 
Treatment  
Visit 3 
Day 71 (+ 5 d) / 
End of Study / 
Early Termination 
Unscheduled 
Clinic Visita 
Investigator cellulite assessments: 
 Selection of dimples to be treated within the 
two buttocks 
 
Xc 
Xc 
Xc 
 
 
 Marking the dimples and injection sites to be 
treated within the buttocks 
 
Xc 
Xc 
Xc 
 
 
 Clinician Reported Photonumeric Cellulite 
Severity Scale (CR-PCSS) 
X 
Xc,h 
Xc,h 
Xc,h 
Xh 
 
 Hexsel Cellulite Severity Scale (CSS) 
Xh,i 
Xc,h,i 
 
 
 
 
 Investigator Global Aesthetic Improvement 
(I-GAIS)  
 
 
Xc,h 
Xc,h 
Xc,h 
 
Confirm eligibility 
 
Xc 
 
 
 
 
Randomize to treatment 
 
Xc,j 
 
 
 
 
Study drug administration 
 
X 
X 
X 
 
 
Injection site reactions/local tolerability in the 
buttocks 
 
X 
X 
X 
X 
X 
Adverse events 
Monitored Throughout Study 
a During unscheduled visits, the Investigator or designee may perform any study procedure that they deem clinically necessary (eg, vital signs, clinical lab assessments, and 
pregnancy test). 
b Before and after marking the dimples and injection sites. 
c Before injection. 
d Up to 4 hours before injection; approximately 15 and 30 minutes after injection. Vital signs must be stable before the subject is discharged. 
e Serum pregnancy test on Screening visit and Day 71/EOS visit; urine pregnancy test on Day 1, Day 22, and Day 43 visits. 
f Subject assessments should be completed independently and prior to Investigator assessments at each visit. 
g Assessment made via photographs (if treatment visit, use photographs taken before marking dimples and injection sites). 
h Assessment of each of the 2 buttocks independently. 
i Initial Hexsel CSS at Screening must be ≤13 on each of 2 bilateral buttocks and the buttocks must again be ≤13 at Day 1 visit  
j Before randomization, each of the subject’s buttocks must have ratings of 3 or 4 (moderate or severe) in both the CR-PCSS and PR-PCSS, and Hexsel CSS score ≤13. 
NOTE: Subject cellulite assessments must be completed before the Investigator cellulite assessments are conducted at each visit.  
d=Days; ECG=Electrocardiogram; EFP=Edematous fibrosclerotic panniculopathy; EOS=End of study 

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6. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES 
TABLE OF CONTENTS 
1. 
TITLE PAGE ................................................................................................................1 
2. 
SUMMARY OF CHANGES ........................................................................................2 
3. 
SPONSOR CONTACT INFORMATION ...................................................................3 
4. 
SYNOPSIS ...................................................................................................................4 
5. 
SCHEDULE OF EVENTS .........................................................................................14 
6. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............16 
7. 
LIST OF ABBREVIATIONS .....................................................................................22 
8. 
INTRODUCTION ......................................................................................................23 
8.1. 
Background .................................................................................................................23 
8.1.1. 
Edematous Fibrosclerotic Panniculopathy .................................................................23 
8.1.2. 
Current EFP Treatments .............................................................................................23 
8.1.3. 
EN3835 (Collagenase Clostridium Histolyticum) ......................................................24 
8.2. 
Summary of Nonclinical Studies ................................................................................25 
8.3. 
Summary of Known Risks and Benefits .....................................................................25 
8.4. 
Rationale .....................................................................................................................26 
9. 
OBJECTIVES .............................................................................................................27 
9.1. 
Primary Objective .......................................................................................................27 
9.2. 
Secondary Objectives .................................................................................................27 
9.3. 
Exploratory Objectives ...............................................................................................27 
10. 
INVESTIGATIONAL PLAN .....................................................................................28 
10.1. 
Study Design ...............................................................................................................28 
10.2. 
Selection of Doses ......................................................................................................28 
10.3. 
Study Drug Administration .........................................................................................29 
10.4. 
Care Procedures After Injection .................................................................................31 
10.5. 
Discussion of Study Design, Including the Choice of Control Groups ......................31 
11. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................32 
11.1. 
Subject Inclusion Criteria ...........................................................................................32 
11.2. 
Subject Exclusion Criteria ..........................................................................................32 
11.3. 
Subject Discontinuation Criteria .................................................................................34 

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11.3.1. 
Replacement Procedures .............................................................................................34 
12. 
TREATMENT OF SUBJECTS ..................................................................................35 
12.1. 
Study Visits .................................................................................................................35 
12.1.1. 
Informed Consent .......................................................................................................35 
12.1.2. 
Subject Screening .......................................................................................................35 
12.1.2.1. 
Medical History ..........................................................................................................35 
12.1.2.2. 
Screening Period (Day -14 to Day -1) ........................................................................35 
12.2. 
Selecting and Marking Dimples during Treatment Visits ..........................................36 
12.3. 
Digital Photography during Treatment Visits 1, 2, and 3 ...........................................38 
12.4. 
Treatment Visit 1 (Day 1) ...........................................................................................38 
12.4.1. 
Treatment Visit 1: Pre-Injection .................................................................................38 
12.4.2. 
Treatment Visit 1: Injection and Post-injection ..........................................................38 
12.5. 
Treatment Visit 2 (Day 22 [±3 days]) and Treatment Visit 3 (Day 43 [±3 
days]) ..........................................................................................................................39 
12.5.1. 
Treatment Visits 2 and 3: Pre-injection ......................................................................39 
12.5.2. 
Treatment Visits 2 and 3: Injection and Post-injection ..............................................39 
12.6. 
Day 71 (+5 days) End of Study / Early Termination ..................................................40 
12.7. 
Unscheduled Visits .....................................................................................................40 
12.8. 
Prior and Concomitant Medications and Procedures ..................................................40 
12.8.1. 
Prohibited Medications or Procedures ........................................................................41 
12.9. 
Treatment Compliance ................................................................................................41 
12.10. 
Blinding and Randomization ......................................................................................41 
13. 
ASSESSMENT OF EFFICACY ................................................................................43 
13.1. 
Efficacy Measurements ..............................................................................................43 
13.1.1. 
Digital Photography ....................................................................................................43 
13.1.2. 
Subject and Investigator Cellulite Assessments .........................................................43 
13.1.2.1. 
Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) ........................43 
13.1.2.2. 
Subject Global Aesthetic Improvement Scale (S-GAIS) ............................................44 
13.1.2.3. 
Subject Satisfaction with Cellulite Treatment Assessment ........................................45 
13.1.2.4. 
Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) ....................45 
13.1.2.5. 
Investigator Global Aesthetic Improvement Scale (I-GAIS) .....................................46 
13.1.2.6. 
Hexsel Cellulite Severity Scale ..................................................................................46 
14. 
ASSESSMENT OF SAFETY .....................................................................................48 

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14.1. 
Definitions ..................................................................................................................48 
14.1.1. 
Adverse Events ...........................................................................................................48 
14.1.2. 
Serious Adverse Events ..............................................................................................48 
14.2. 
Monitoring Adverse Events ........................................................................................49 
14.3. 
Relationship to Study Drug ........................................................................................49 
14.4. 
Intensity Assessment ..................................................................................................50 
14.5. 
Reporting Adverse Events and Serious Adverse Events ............................................50 
14.5.1. 
Reporting Adverse Events ..........................................................................................50 
14.5.2. 
Reporting Serious Adverse Events .............................................................................50 
14.5.2.1. 
Follow-up Procedures for Serious Adverse Events ....................................................51 
14.6. 
Special Reporting Situations .......................................................................................51 
14.6.1. 
Adverse Events of Special Interest .............................................................................51 
14.6.2. 
Overdose/Misuse/Abuse .............................................................................................51 
14.6.2.1. 
Overdose .....................................................................................................................51 
14.6.3. 
Pregnancy ...................................................................................................................52 
14.6.4. 
AEs/SAEs Experienced by Non-subjects Exposed to Study Medication ...................52 
14.7. 
Clinical Laboratory Determinations ...........................................................................52 
14.8. 
Anti-AUX-I and Anti-AUX-II Antibodies .................................................................54 
14.9. 
Vital Signs ..................................................................................................................54 
14.10. 
Electrocardiogram .......................................................................................................54 
14.11. 
Physical Examination .................................................................................................55 
14.12. 
Other Safety Assessments ...........................................................................................55 
15. 
ASSESSMENT OF PHARMACOKINETICS ...........................................................56 
16. 
ASSESSMENT OF PHARMACODYNAMICS ........................................................57 
17. 
STATISTICAL CONSIDERATIONS AND METHODS .........................................58 
17.1. 
Determination of Sample Size ....................................................................................58 
17.2. 
Subject Populations ....................................................................................................58 
17.2.1. 
Safety Population ........................................................................................................58 
17.2.2. 
Intent-to-Treat (ITT) Population .................................................................................59 
17.2.3. 
Modified Intent-to-Treat (mITT) Population ..............................................................59 
17.2.4. 
Per-Protocol (PP) Population ......................................................................................59 
17.3. 
Subject Disposition .....................................................................................................59 
17.4. 
Demographics and Other Baseline Characteristics .....................................................59 

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17.5. 
Efficacy Analyses .......................................................................................................60 
17.5.1. 
Primary Efficacy Variable ..........................................................................................60 
17.5.2. 
Secondary Efficacy Variables .....................................................................................61 
17.5.2.1. 
Key Secondary Variables ...........................................................................................61 
17.5.3. 
Supportive Efficacy Variables ....................................................................................61 
17.5.3.1. 
Supportive Variables ..................................................................................................61 
17.6. 
Safety Analyses ..........................................................................................................64 
17.6.1. 
Prior, Concomitant, and Follow-up Medication .........................................................64 
17.6.2. 
Study Drug Exposure ..................................................................................................65 
17.6.3. 
Measurement of Treatment Compliance ....................................................................65 
17.6.4. 
Adverse Events ...........................................................................................................65 
17.6.5. 
Vital Signs ..................................................................................................................66 
17.6.6. 
Clinical Laboratory Parameters ..................................................................................66 
17.6.7. 
Electrocardiogram .......................................................................................................66 
17.6.8. 
Physical Examination .................................................................................................66 
17.6.9. 
Other Safety Measurements ........................................................................................66 
17.7. 
Pharmacokinetic Analyses ..........................................................................................67 
17.8. 
Pharmacodynamic Analyses .......................................................................................67 
17.9. 
Other Data (eg, Health Economics/QOL, Pharmacogenetic, etc) ..............................67 
17.10. 
Interim Analysis ..........................................................................................................67 
17.11. 
Statistical Software .....................................................................................................67 
18. 
STUDY DRUG MATERIALS AND MANAGEMENT ...........................................68 
18.1. 
Study Drug Identity ....................................................................................................68 
18.2. 
Study Drug Packaging and Labeling ..........................................................................68 
18.3. 
Study Drug Storage .....................................................................................................68 
18.4. 
Study Drug Preparation ..............................................................................................68 
18.5. 
Study Drug Accountability .........................................................................................69 
18.5.1. 
Study Drug Handling and Disposal ............................................................................69 
19. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS .........................................70 
19.1. 
Source Documents ......................................................................................................70 
19.2. 
Study Monitoring ........................................................................................................70 
19.3. 
Audits and Inspections ................................................................................................70 
19.4. 
Institutional Review Board (IRB) ...............................................................................70 

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19.5. 
Data Recording and Documentation ...........................................................................71 
20. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................72 
21. 
ETHICS ......................................................................................................................73 
21.1. 
Ethics Review .............................................................................................................73 
21.2. 
Ethical Conduct of the Study ......................................................................................73 
21.3. 
Subject Information and Consent ...............................................................................74 
22. 
DATA HANDLING AND RECORDKEEPING .......................................................75 
22.1. 
Data Collection ...........................................................................................................75 
22.2. 
Study Documentation .................................................................................................75 
23. 
REPORTING AND PUBLICATION .........................................................................76 
24. 
INVESTIGATOR OBLIGATIONS ...........................................................................77 
24.1. 
Regulatory Documents ...............................................................................................77 
24.2. 
Delegation of Responsibilities and Adequate Resources ...........................................78 
24.3. 
Medical Care of Study Subjects .................................................................................78 
24.4. 
Use of Investigational Materials .................................................................................78 
24.5. 
Retention of Records ..................................................................................................78 
24.6. 
Subject Confidentiality ...............................................................................................79 
25. 
TERMINATION OF STUDY ....................................................................................80 
26. 
INVESTIGATOR’S STATEMENT ...........................................................................81 
27. 
REFERENCES ...........................................................................................................82 
APPENDIX A. DOCUMENTS REQUIRED PRIOR TO INITIATION OF THE 
STUDY .......................................................................................................................83 
APPENDIX B. PATIENT-REPORTED PHOTONUMERIC CELLULITE SEVERITY 
SCALE (PR-PCSS) FOR THE BUTTOCK ...............................................................85 
APPENDIX C. CLINICIAN-REPORTED PHOTONUMERIC CELLULITE 
SEVERITY SCALE (CR-PCSS) FOR THE BUTTOCK ..........................................86 
APPENDIX D. HEXSEL DM, DAL’FORNO T, HEXSEL CL. A VALIDATED 
PHOTONUMERIC CELLULITE SEVERITY SCALE. J EUR ACAD 
DERMATOL VENEREOL. 2009;23(5):523-8 ............................................................87 
APPENDIX E. REFERENCE IMAGES FOR HEXSEL SEVERITY RATINGS .....................95 
 

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LIST OF TABLES 
Table 1: 
Sponsor Contact Information ........................................................................................3 
Table 2: 
Abbreviations and Special Terms ...............................................................................22 
Table 3:  
Study Treatment Groups .............................................................................................28 
Table 4: 
Concomitant Medication Restrictions for Subjects during the Treatment 
Phase of Study ............................................................................................................41 
Table 5: 
Subject Global Aesthetic Improvement Scale (S-GAIS) ............................................44 
Table 6: 
Subject Satisfaction with Cellulite Treatment Assessment - Buttocks .......................45 
Table 7: 
Investigator Global Aesthetic Improvement Scale (I-GAIS) .....................................46 
Table 8: 
Hexsel Cellulite Severity Scale ..................................................................................47 
Table 9: 
Clinical Laboratory Tests ...........................................................................................53 
Table 10: Vital Signs Measurements on Injection Day ..............................................................54 
Table 11: Fitzpatrick Scale .........................................................................................................55 
 
LIST OF FIGURES 
Figure 1: 
Study Design ...............................................................................................................28 
Figure 2: 
Study Drug Administration at Each Injection Site .....................................................30 
 
 

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7. 
LIST OF ABBREVIATIONS  
The following abbreviations and specialized terms are used in this study protocol. 
Table 2: 
Abbreviations and Special Terms 
Abbreviation 
Definition 
AE 
Adverse event 
AUX-I 
Clostridial class I collagenase 
AUX-II 
Clostridial class II collagenase 
BMI 
Body mass index 
CR-PCSS 
Clinician Reported Photonumeric Cellulite Severity Scale 
CSS 
Cellulite severity scale 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
EFP 
Edematous fibrosclerotic panniculopathy 
ePRO 
Electronic patient reported outcome 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HREC 
Human Research Ethics Committee 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
I-GAIS 
Investigator-Global Aesthetic Improvement Scale 
IRB 
Institutional Review Board 
ITT 
Intent-to-treat 
IWRS 
Interactive web response system 
LOCF 
Last observation carried forward 
mITT 
Modified intent-to-treat 
PR-PCSS 
Patient Reported Photonumeric Cellulite Severity Scale 
Quadrant 
A quadrant is a treatment area 
Qualified designee 
Qualified by education and training to perform the study procedure (eg, 
sub-Investigator, nurse). 
SAE 
Serious adverse event 
S-GAIS 
Subject – Global Aesthetic Improvement Scale 
TEAE 
Treatment-emergent adverse event. Adverse events that occur on or after the 
first injection of study drug. 

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8. 
INTRODUCTION 
8.1. 
Background 
8.1.1. 
Edematous Fibrosclerotic Panniculopathy 
Edematous fibrosclerotic panniculopathy (EFP), commonly known as cellulite, has been defined 
as a local metabolic disorder of subcutaneous tissues that results in a contour abnormality of the 
skin.(1) The condition manifests as dimpled skin, particularly in the gluteal-femoral region.(2,3) 
EFP is caused by herniation of subcutaneous fat lobules through the dermohypodermal junction 
and/or shortening of the collagen septa that cross the hypodermal layer and connects the dermis 
to the underlying fascia. This creates an uneven surface with dimpling.(1,2) EFP is a medical 
condition resulting in a potentially cosmetically unacceptable alteration of the skin, and affects 
an estimated 85% to 98% of postpubertal women.(1,3) 
The pathophysiology of EFP is not completely understood, but there are 3 main theories: edema 
resulting from excessive hydrophilia of the intercellular matrix, alteration of the regional 
microcirculation, and different anatomical conformation of collagenous subcutaneous tissues in 
women versus men.(4) 
It is known that EFP is different from generalized obesity. In generalized obesity, adipocytes 
undergo hypertrophy and hyperplasia that are not limited to the pelvis, thighs, and abdomen.(1) 
In areas of EFP, adipocytes have physiologic and biochemical properties that differ from adipose 
tissue located elsewhere. Large, metabolically-stable adipocytes characterize EFP-prone areas; 
thus, the responsiveness to catecholamine-induced lipolysis is less in EFP tissues compared to 
visceral fat, which has the greatest responsiveness.(1) 
Subcutaneous fat lobes are separated from one another by thin, usually rigid strands of 
collagenous connective tissues, which cross the fatty layers and connect the dermis to the 
underlying fascia. These septa stabilize the subcutis and divide the fat. In EFP, shortening of the 
collagen septa due to fibrosis provokes retraction at the insertion points of the trabeculae, 
causing the depressions that characterize EFP.(2) There are a higher percentage of thinner, 
perpendicular hypodermal septa in women with EFP than in men.(1) Weight gain makes EFP 
more noticeable, but it may be present even in thin subjects. Genetics may also play a role since 
EFP tends to run in families. 
8.1.2. 
Current EFP Treatments 
There are therapies that have been utilized in an attempt to treat cellulite; however, there are no 
approved pharmacologic treatments. Despite multiple therapeutic modalities, there is little 
scientific evidence that any of these treatments are beneficial. In fact, much of the evidence is 
anecdotal, subjective, or based only on patient self-assessment.(5) Some of the historical 
treatments for EFP have included weight loss,(6) topical agents,(5) massage,(7) liposuction,(5,6) 
mesotherapy,(6) radiofrequency,(6) subcision and powered subcision,(8) and laser 
therapies;(9,10) some of these treatments may pose an increased risk for adverse effects.(5) 

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There remains an unmet medical need for safe and effective therapies to improve the aesthetic 
outcome in women with cellulite. To effectively treat cellulite, a therapeutic approach may 
require disruption of the dermal septa, which are composed of collagen and cause the skin 
dimpling that is bothersome to many women. 
8.1.3. 
EN3835 (Collagenase Clostridium Histolyticum) 
Endo Pharmaceuticals Inc. (Endo) is developing EN3835 for the treatment of EFP. Because 
EN3835 is a proteinase that can hydrolyze the triple-helical region of collagen under 
physiological conditions, EN3835 has the potential to be effective in lysing subdermal collagen, 
such as those observed in the dermal septa, which are the underlying cause of the skin dimpling 
in women with EFP. EN3835 targets the collagenase structural matrix (eg, dermal septa) at the 
site of injection and does not require systemic exposure to be effective. 
EN3835 is a parenteral lyophilized product comprised of 2 collagenases in an approximate 1:1 
mass ratio, Collagenase I (AUX-I, Clostridial class I collagenase) and Collagenase II (AUX-II; 
Clostridial class II collagenase). These collagenases are isolated and purified from the 
fermentation of Clostridium histolyticum. 
Collagenase AUX-I is a single polypeptide chain containing approximately 1,000 amino acids of 
known sequence and with a molecular weight of 114 kDa. Collagenase AUX-II is also 
approximately 1,000 amino acids long and has a molecular weight of 113 kDa. These 
2 collagenases are not immunologically cross-reactive and have different specificities, such that 
together they become synergistic, providing a very broad hydrolyzing reactivity toward collagen. 
Clostridial collagenases are proteinases that can hydrolyze the triple-helical region of collagen 
under physiological conditions. 
EN3835 is currently approved (brand name is XIAFLEX®) for: 1) the treatment of adults with 
Dupuytren’s contracture with a palpable cord and, 2) for the treatment of adult men with 
Peyronie’s disease with a palpable plaque and curvature deformity of at least 30° at the start of 
therapy. 
A recent Phase 2b, randomized, double-blind, placebo-controlled study (EN3835-201) of 
375 women randomized to treatment of one treatment area (quadrant) (quadrant was defined in 
study EN3835-201 as a left buttock, a right buttock, a left posterolateral thigh or a right 
posterolateral thigh) of cellulite with EN3835 0.84 mg or placebo in a 1:1 ratio assessed the 
effectiveness and safety of EN3835. Efficacy in this study was evaluated based on cellulite 
assessments using Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS), Patient 
Reported Photonumeric Cellulite Severity Scale (PR-PCSS), Investigator Global Aesthetic 
Improvement Scale (GAIS-I), Subject Global Aesthetic Improvement Scale (GAIS-S), and 
Subject Satisfaction with Cellulite Treatment. 
Results from the Phase 2b study demonstrated that treatment (3 visits approximately 21 days 
apart) improved the cellulite severity of the treatment area as assessed by the primary endpoint of 
2-level composite responder analyses, the proportion of responders based on an improvement of 
≥2 levels in the appearance of cellulite in both the patient PR-PCSS and the clinician CR-PCSS 
of buttocks and thighs was statistically significantly greater in subjects who received EN3835 
0.84 mg (10.6%; p<0.001) compared to subjects who received placebo (1.6%); 1-level (or 
greater) responders in the PR-PCSS of EN3835-treated subjects (72.3%) was significantly 

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greater than 1-level responders in the placebo group (51.6%) (p<0.001); statistically significant 
(p≤0.001) improvement in the appearance of cellulite based on the subject S-GAIS were 
observed in EN3835 0.84-mg group (73.1%) compared to the placebo group (44.0%); and 62.9% 
of subjects in the EN3835 0.84 mg group were satisfied or very satisfied with the results of their 
cellulite treatment compared with only 35.9% of subjects in the placebo group (p<0.001). In 
subjects treated in buttocks (n=187), the proportion of 2-level composite responders was 
statistically significantly greater in subjects who received EN3835 0.84 mg (14.9%; p<0.001) 
compared to subjects who received placebo (1.1%); 1-level (or greater) responders in the 
PR-PCSS of EN3835-treated subjects (72.7%) was significantly greater than 1-level responders 
in the placebo group (47.8%) (p<0.001). 
The study also demonstrated EN3835 to be well tolerated with no serious adverse events (SAEs) 
related to EN3835. Safety results from a total of 4 studies (1 pilot, 2 Phase 1, and 2 Phase 2 
studies) in which 435 adult females received subcutaneous injections of EN3835 indicate that the 
majority of treatment-emergent adverse events (TEAEs) are transient, non-serious, mild or 
moderate in intensity, and related to the local administration of EN3835. The immunogenicity 
profile after 3 treatment visits of EN3835 indicate that greater than 90% of EN3835-treated 
subjects were seropositive for AUX-I and/or AUX-II antibodies; this profile of EN3835 is 
similar to that observed in the Dupuytren’s contracture and Peyronie’s disease programs. 
A Phase 1, open-label safety and pharmacokinetic study of a single dose of EN3835 0.84 mg in 
11 female subjects with EFP showed that there was no quantifiable levels of AUX-I or AUX-II 
at any time point after subcutaneous injection of EN3835 0.84 mg into one quadrant. A second 
Phase 1, open-label safety and pharmacokinetic study of a single dose of EN3835 0.84 mg per 
treatment area in two treatment areas (buttock-buttock, thigh-thigh, or buttock-thigh) 
concurrently (total dose of 1.68 mg) showed that there was no quantifiable levels of AUX-I or 
AUX-II at any time point post-dose attributable to the injection of EN3835 1.68 mg. 
The results from these studies suggest that subcutaneous injections of EN3835 in the area of 
cellulite may be a well-tolerated and effective medical treatment for adults with EFP. 
8.2. 
Summary of Nonclinical Studies 
Non-clinical studies necessary to support clinical studies have been performed and are 
summarized in the Investigator Brochure (IB).(11) Non-clinical studies in the following areas 
were performed: toxicology, reprotoxicity, genotoxicity, and hypersensitivity. 
8.3. 
Summary of Known Risks and Benefits 
A summary of safety risks is provided in the IB.(11) The following events have been commonly 
observed: local injection site reactions (injection site bruising, injection site swelling, injection 
site pain) for the various approved indications as well as those being investigated. In the phase 
2b study of EN3835 in women with EFP, the following treatment related adverse events ≥2% of 
189 EN3835-treated women were reported: injection site bruising (75.1%), injection site pain 
(59.3%), injection site nodule (14.3%), injection site pruritus (11.1%), injection site swelling 
(7.4%), injection site induration (5.8%), injection site mass (5.3%), injection site discolouration 
(3.2%), and injection site erythema (2.1%). These events are similar to events reported in the 
clinical trials of EN3835 for the approved indications. Postmarketing safety data are consistent 
with safety data reported in clinical trials. 

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Although a thorough benefit of EN3835 has not been fully evaluated in the treatment of EFP, the 
efficacy results from the Phase 2b study and previous EFP studies warranted further 
development. 
8.4. 
Rationale 
The results from the Phase 2b EFP study (EN3835-201) further suggested that EN3835 0.84 mg 
per treatment area (quadrant) is an effective treatment of EFP based on improvement in the 
severity of cellulite as determined by the Investigator and the subject. There were no safety 
concerns following 0.84 mg per treatment area in the treatment of EFP (section 8.1.3). Safety 
findings from the Phase 2b EFP study are similar to that observed in previous clinical studies 
with EN3835 in the treatment of EFP and XIAFLEX in the treatment of Dupuytren’s contracture 
and Peyronie’s disease, in that that the majority of AEs occurred at the site of injection and 
resolved before the next scheduled treatment. The immunogenicity profile of EN3835 in the 
Phase 2b EFP study is similar in previous studies and programs. 
Based on the efficacy and safety findings from the Phase 2a and 2b EFP studies, the EN3835 
0.84-mg dose per treatment area in two treatment areas (buttocks) warranted further investigation 
in this study. 
Treating two buttocks at each treatment visit will potentially provide a symmetrical-like 
improvement in appearance. Support for evaluation of the treatment of two buttocks concurrently 
is based on: 1) the safety findings from the previous EFP studies are local to the injection site, 
2) the pharmacological activity of EN3835 is local and does not require systemic exposure, and 
3) no significant quantifiable systemic concentration has been attributable to injection of two 
buttocks concurrently. 
The integration of dose and use justification supports this study of evaluation of EN3835 
0.84 mg per treatment area in two treatment areas (buttocks) concurrently. 
 

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9. 
OBJECTIVES 
9.1. 
Primary Objective 
The primary objective of this study is to assess the efficacy and safety of EN3835 in the 
treatment of edematous fibrosclerotic panniculopathy (EFP) commonly known as cellulite in 
adult women. 
9.2. 
Secondary Objectives 
There are no secondary objectives of this study. 
9.3. 
Exploratory Objectives 
There are no exploratory objectives of this study. 
 

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10. 
INVESTIGATIONAL PLAN 
10.1. 
Study Design 
This study will be performed at approximately 25 study centers located in the United States. This 
clinical study will be conducted as a multicenter, randomized, double-blind, placebo-controlled 
study comparing EN3835 to placebo in adult women with EFP. The study will consist of 71 days 
of double-blind treatment. Subjects meeting the entry criteria for this study will be randomized to 
EN3835 treatment or placebo treatment in a 1:1 ratio within an investigational site.  
The complete Schedule of Events is provided in section 5. 
Figure 1: 
Study Design 
 
Table 3:  
Study Treatment Groups 
Dose per 
Each Injectiona / 
Number of 
Subjects 
Injection 
Volume per 
Each Injection 
Number of 
Injections at Each 
Treatment Visit 
Dose (mg) at Each 
Treatment Visit 
Injection Volume 
(mL) per Each 
Treatment Visit 
Cumulative EFP 
Dose 
EN3835 0.07 mg / 
N=210 
0.3 mL 
12 per buttock  
× 2 buttocks =  
24 injections 
0.84 mg per buttock  
× 2 buttocks = 
1.68 mg 
(12 injections  
per buttock ×  
0.07 mg/injection ×  
2 buttocks) 
3.6 mL per buttock  
× 2 buttocks = 
7.2 mL  
(24 injections × 
0.3 mL) 
5.04 mg 
(3 treatment visits × 
0.84 mg per buttock 
× 2 buttocks) 
Placebo /  
N=210 
0.3 mL 
12 per buttock  
× 2 buttocks =  
24 injections 
- 
3.6 mL per buttock  
× 2 buttocks = 
7.2 mL  
(24 injections × 
0.3 mL) 
- 
a Each injection of study drug is 0.3 mL administered as three 0.1 mL aliquots. 
10.2. 
Selection of Doses 
The dose of EN3835 chosen for this study was based on the results from earlier studies. 
The data from the Phase 2a EFP dose-ranging study (AUX-CC-831) suggest that EN3835 
0.84 mg is most effective in the treatment of EFP based on improvement in the severity of 

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cellulite as determined by both the Investigator and the subject, although the EN3835 0.48-mg 
group did show improvement in some of the efficacy parameters. 
 There were no safety concerns following administration of up to 3 treatment visits of 
EN3835 0.84 mg in the treatment of EFP (AUX-CC-831 CSR). The safety profile of 
EN3835 0.84 mg in the treatment of EFP was similar to that observed in the EN3835 
0.06-mg group and the EN3835 0.48-mg group. No notable differences were 
observed across the 3 treatment groups. 
 Safety findings from the Phase 2a EFP dose-ranging study are similar to that 
observed in previous clinical studies with XIAFLEX in the treatment of Dupuytren’s 
contracture and Peyronie’s disease, in that the majority of AEs occurred at the site of 
injection and resolved before the next scheduled treatment. 
 The immunogenicity profile of EN3835 in the Phase 2a EFP dose-ranging study is 
similar to that observed in the Dupuytren’s contracture and Peyronie’s disease 
programs. 
 Based on the efficacy and safety findings from the Phase 2a EFP dose-ranging study, 
the EN3835 0.84-mg dose was carried forward to the Phase 2b study. 
The results from the Phase 2b EFP study (EN3835-201) further suggested that EN3835 0.84 mg 
is an effective treatment of EFP based on improvement in the severity of cellulite as determined 
by the Investigator and the subject. There were no safety concerns following EN3835 0.84 mg 
in the treatment of EFP (section 8.4). Safety findings from the Phase 2b EFP study are similar to 
that observed in previous clinical studies with XIAFLEX in the treatment of Dupuytren’s 
contracture and Peyronie’s disease, in that that the majority of AEs occurred at the site of 
injection and resolved before the next scheduled treatment. The immunogenicity profile of 
EN3835 in the Phase 2b EFP study is similar to that observed in the Dupuytren’s contracture 
and Peyronie’s disease programs. 
Based on the efficacy and safety findings from the Phase 2a and 2b EFP studies, the EN3835 
0.84-mg dose per treatment area was carried forward to this study. The findings from previous 
studies that the majority of adverse events after EN3835 treatment are local to the injection site 
and that there is no quantifiable systemic exposure observed after concurrent treatment of two 
buttocks (total dose of 1.68 mg) supports the proposed study to evaluate EN3835 treatment of 
two buttocks. 
10.3. 
Study Drug Administration 
Study drug will be injected subcutaneously while the subject is in a prone position using a 
syringe with a 30-gauge ½-inch needle. Each injection site will receive a single skin injection of 
study drug administered as three 0.1-mL aliquots to Positions A, B, and C (for a total injection 
volume of 0.3 mL) as shown in the following figure. The depth of injection corresponds to the 
length of the treatment needle (0.5 inches) from the tip of the needle to the hub or base of the 
needle without downward pressure. 
During each treatment visit, 8 syringes (4 syringes per buttock) will be prepared for dosing. Each 
syringe will contain 0.9 mL of study drug (ie, 3 injections in each syringe). Twelve (12) skin 

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10.4. 
Care Procedures After Injection 
To evaluate the subject for possible immediate immunological AEs, the subject will remain in 
direct observation of medical personnel who are skilled in the management of an allergic 
reaction for 30 minutes after receiving the injections of study drug and until the subject exhibits 
no sign of an immunological or other clinically significant systemic or local AE. The subject’s 
vital signs should be stable before the subject can leave direct observation (see section 14.9). 
The Investigator or qualified designee will then apply a sterile dressing to the injection areas 
with hypoallergenic tape. The subject will be instructed to remove the dressing in the evening. 
10.5. 
Discussion of Study Design, Including the Choice of Control Groups 
The design of this study was based on the primary objective to evaluate the efficacy and safety of 
EN3835 0.84 mg per buttock in the concurrent treatment (total dose of 1.68 mg) of 2 bilateral 
buttocks with EFP in adult women compared with placebo treatment. The study design, a 
multi-center, double-blind, placebo-controlled study is in accordance with regulatory guidelines 
of adequate and well-controlled clinical studies (Food and Drug Administration [FDA] Guidance 
for Industry: Providing Clinical Evidence of Effectiveness for Human Drug and Biological 
Products, 1998.; ICH E8 and E10). 
 

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11. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
11.1. 
Subject Inclusion Criteria 
In order to be eligible to participate in the study, subjects must meet the following criteria: 
1. Voluntarily sign and date an informed consent agreement 
2. Be a female ≥18 years of age 
3. At Screening visit, have 2 bilateral buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as reported by the Investigator (CR-PCSS), and 
c. a Hexsel CSS score no greater than 13 
4. At Day 1 visit, have 2 bilateral buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as reported by the Investigator (CR-PCSS), and 
c. a Hexsel CSS score no greater than 13 
5. Be willing to apply sunscreen to the buttocks before each exposure to the sun while 
participating in the study (ie, Screening through end of study) 
6. Be judged to be in good health, based upon the results of a medical history, physical 
examination, and laboratory profile at Screening 
7. Have a negative serum pregnancy test at Screening and a negative urine pregnancy test 
before injection of study drug and be using a stable and effective contraception method 
(eg, abstinence, intrauterine device [IUD], hormonal [estrogen/progestin] contraceptives, 
or double barrier method) for at least 1 menstrual cycle prior to study enrollment and for 
the duration of the study; or be menopausal defined as 12 months of amenorrhea in the 
absence of other biological or physiological causes, as determined by the Investigator; or 
post-menopausal for at least 1 year; or be surgically sterile 
8. Be willing and able to cooperate with the requirements of the study 
9. Be able to read, complete and understand the patient-reported outcomes rating 
instruments in English 
11.2. 
Subject Exclusion Criteria 
Subjects who meet any of the following criteria will not be eligible to participate in the study: 
1. Has any of the following systemic conditions: 
a. Coagulation disorder 
b. Evidence or history of malignancy (other than excised basal-cell carcinoma) unless 
there has been no recurrence in at least 5 years 
c. History of keloidal scarring or abnormal wound healing 

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d. Concurrent diseases or conditions that might interfere with the conduct of the study, 
confound the interpretation of the study results, or endanger the subject’s well-being. 
Any questions about concurrent diseases should be discussed with the Medical 
Monitor 
e. Evidence of clinically significant abnormalities on physical examination, vital signs, 
electrocardiogram (ECG), or clinical laboratory values 
2. Has any of the following local conditions in the areas to be treated: 
a. History of lower extremity thrombosis or post-thrombosis syndrome 
b. Vascular disorder (eg, varicose veins, telangiectasia) in area to be treated 
c. Inflammation or active infection 
d. Active cutaneous alteration including rash, eczema, psoriasis, or skin cancer 
e. Has a tattoo and/or a mole located within 2 cm of the site of injection 
3. Requires the following concomitant medications before or during participation in the 
trial: 
a. Anticoagulant or antiplatelet medication or has received anticoagulant or antiplatelet 
medication (except for ≤150 mg aspirin daily) within 7 days before injection of study 
drug 
4. Has used any of the following for the treatment of EFP on a buttock within the timelines 
identified below or intends to use any of the following at any time during the course of 
the study: 
a. Liposuction in a buttock during the 12-month period before injection of study drug 
b. Injections (eg, mesotherapy); radiofrequency device treatments; laser treatment; 
buttock implant treatment; cryolipolysis; or surgery (including subcision and/or 
powered subcision) within a buttock during the 12-month period before injection of 
study drug 
c. Any investigational treatment for EFP on a buttock during the 12-month period 
before the injection of study drug 
d. Endermologie or similar treatments within a buttock during the 6-month period 
before injection of study drug 
e. Massage therapy within a buttock during the 3-month period before injection of study 
drug 
f. Creams (eg, Celluvera™, TriLastin®) and/or home therapies to prevent or mitigate 
EFP within a buttock during the 2-week period before injection of study drug 
5. Is presently nursing or providing breast milk 
6. Intends to become pregnant during the study 
7. Intends to initiate an intensive sport or exercise program during the study 
8. Intends to initiate a weight reduction program during the study 
9. Intends to use tanning spray or tanning booths during the study 

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10. Has received an investigational drug or treatment within 30 days before injection of study 
drug 
11. Has a known systemic allergy to collagenase or any other excipient of study drug 
12. Has received any collagenase treatments at any time prior to treatment 
13. Was a subject in a previous cellulite clinical trial of CCH: AUX-CC-830, AUX-CC-831, 
EN3835-102, EN3835-104, EN3835-201, and/or EN3835-202 
14. Any other condition(s) that, in the Investigator’s opinion, might indicate the subject to be 
unsuitable for the study  
11.3. 
Subject Discontinuation Criteria 
A premature discontinuation will occur when a subject who signed informed consent ceases 
participation in the study, regardless of circumstances, prior to the completion of the protocol. 
Subjects can be prematurely discontinued from the study for one of the following reasons: 
 An adverse event 
 Lack of efficacy 
 A protocol violation (reason must be specified, for example: lack of compliance, use 
of a prohibited concomitant medication, failure to meet inclusion/exclusion criteria 
after study entry, etc) 
 Withdrawal by subject (reason must be specified) 
 The subject was “lost to follow-up” 
 Other reasons (reason must be specified, for example: the subject moved, pregnancy, 
Investigator decision, Sponsor decision to terminate trial, etc) 
If a subject discontinues from the study, all end-of-study procedures including safety and 
efficacy assessments should be conducted as detailed in the Schedule of Events (section 5). The 
date a subject discontinues and the reason for discontinuation will be recorded in the source 
documentation and electronic case report form (eCRF). If, however, a subject withdraws consent, 
no end-of-study procedures and assessments are required (but are encouraged to reduce missing 
information) except the collection of adverse event (AE) information. This information should be 
recorded in the source documentation and the eCRF. 
11.3.1. 
Replacement Procedures 
Subjects who discontinue from the study will not be replaced. 

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12. 
TREATMENT OF SUBJECTS 
12.1. 
Study Visits 
The Schedule of Events to be performed at each visit is shown in section 5. Provided below are 
further details where additional instruction about the assessments that will be performed is 
deemed to be needed. 
12.1.1. 
Informed Consent 
Signed and dated informed consent will be obtained from each subject before any study 
procedures are undertaken, or before any changes to the subject’s medication regimen are made. 
Details about how the informed consent will be obtained and documented are provided in 
section 21.3, Subject Information and Consent. 
12.1.2. 
Subject Screening 
Investigators will be expected to maintain a Screening log of all potential study subjects. This log 
will include limited information about the potential subject and the date and outcome of the 
screening process (eg, enrolled into the study, reason for ineligibility, or refused to participate). 
Investigators will provide information about the study to subjects who appear to meet the criteria 
for participation in the study. The screening log will be captured directly by the electronic data 
capture (EDC) system. 
12.1.2.1. Medical History 
During the screening period, the Investigator or qualified designee will obtain a medical history 
from each subject that includes relevant diagnoses and/or procedures/therapies with 
onset/resolutions dates. Medical histories should also include history of EFP (start date and 
family history), and history of tobacco and alcohol use (never, current, former). 
12.1.2.2. Screening Period (Day -14 to Day -1) 
Subjects meeting the relevant eligibility criteria listed in section 11 may be enrolled in the study 
after the nature and purpose of the protocol have been explained and written informed consent to 
participate has been voluntarily provided by the subject or their legally authorized representative. 
The subject identification number will consist of 8 digits. The first 4 digits represent the study 
site number followed by a 4-digit subject number. 
The following procedures will be performed and documented during the screening period: 
1. Obtain written informed consent (section 12.1.1) 
2. Evaluate eligibility based on inclusion/exclusion criteria (section 11.1 and section 11.2) 
3. Subject will have digital photographs taken of her two buttocks (section 13.1.1) 
4. Subjects will get instruction on the use of the PR-PCSS (section 13.1.2.1) 

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5. Prior to Investigator CR-PCSS or Hexsel CSS assessment, subjects will rate each of their 
two buttocks using the PR-PCSS while viewing their digital images (section 13.1.2.1); 
the Investigator is blinded to these scores 
6. After the subject has completed the PR-PCSS ratings, the Investigator will conduct live 
assessments of subject’s cellulite severity of each of the two buttocks using the CR-PCSS 
(section 13.1.2.4); the subject is blinded to these ratings 
7. After the Investigator has completed the CR-PCSS ratings, the Investigator will conduct 
live evaluation of each of the two buttocks using the Hexsel CSS; the subject is blinded to 
these ratings. The ratings from the PR-PCSS, CR-PCSS, and Hexsel CSS 
(section 13.1.2.6) will be used to assess initial eligibility of the buttocks for study entry 
8. Medical history including EFP history (section 12.1.2.1) 
9. Record prior and concomitant medications/procedures (section 12.8) 
10. Physical examination including measurement of body weight, height, Fitzpatrick skin 
type (section 14.11) 
11. Vital sign measurements (section 14.9) 
12. 12-lead ECG (section 14.10) 
13. Collection of samples for: 
a. Clinical laboratory testing (section 14.7) 
b. Serum pregnancy testing (section 14.7) 
14. Adverse events (section 14) 
12.2. 
Selecting and Marking Dimples during Treatment Visits 
Selection of dimples to be treated in the two buttocks is at the discretion of the Investigator. 
Dimples must be well-defined and evident when the subject is standing in a consistent, 
standardized relaxed pose (without the use of any manipulation such as skin pinching or muscle 
contraction). Each subject will receive 3 treatment visits of study drug according to 
randomization unless the buttock is dimple-free (score of 0 on CR-PCSS as reported by the 
Investigator) at Treatment Visit 2 and/or Treatment Visit 3 (a dimple -free buttock at Treatment 
Visit 1 is precluded by the eligibility criteria); a dimple-free buttock at Treatment Visit 2 and/or 
Treatment Visit 3 does not preclude treatment of the contralateral buttock unless it is dimple-free 
also. During each treatment visit, each of the buttocks will be photographed before and after 
marking dimples and injection sites while the subject is standing in a consistent, standardized 
relaxed pose as described in the Photography Manual. The cellulite severity assessments using 
the PR-PCSS, CR-PCSS, and Hexsel CSS (note that the Hexsel CSS assessment is performed at 
Screening visit and Day 1 visit only) will be completed prior to marking dimples and injection 
sites. 
The Investigator or qualified designee will select dimples within each buttock that are well-
defined, evident when the subject is standing, and suitable for treatment; treatment consists of 
12 injections per buttock (24 injections total in two buttocks) per treatment visit. Because the 
goal of treatment is to improve the aesthetic appearance of each entire buttock, the Investigator 

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will be instructed to select dimples that in his or her opinion would most improve the aesthetic 
appearance of each entire buttock. The same dimples within a buttock or different dimples within 
a buttock may be treated at each treatment visit but injections must all be within the buttocks 
(12 injections per buttock) for all 3 visits. Each buttock will receive all 3 treatment visits unless 
the buttock has no treatable EFP dimples and the Investigator rates the buttock a score of 0 on 
the CR-PCSS. If no injections in a particular buttock (right or left) are given at Treatment Visit 
2, subjects will still be assessed for treatment in the contralateral buttock at Treatment Visit 2, 
and will return for the Day 43 visit and each of the buttocks will again be evaluated by the 
subject (PR-PCSS) and Investigator (CR-PCSS). If the Investigator rates either or both of the 
buttocks greater than 0 on the CR-PCSS, injections at Treatment Visit 3 should be given. 
For each dimple selected for treatment, the Investigator or qualified designee will choose 
injection sites (injection sites within a dimple should be spaced approximately 2 cm apart, if a 
dimple requires more than 1 injection; locating at least one injection site at the nadir, if present, 
of the dimple). Each injection site will be marked with a “dot” using a surgical marker. For 
round dimples, the “dot” will be placed in the center of the dimple; for elongated dimples, “dots” 
will be spaced out approximately 2 cm along the longer axis of the dimple. The Investigator or 
qualified designee will then use a surgical marker to circle each of the dimples selected for 
treatment. Circles in the buttock should not overlap. 
Each of the buttocks will be photographed before and after marking dimples and injection sites 
while the subject is standing in a consistent, standardized relaxed pose as described in the 
Photography Manual. 
Examples of subject dimple and injection site markings are shown as follows: 
Sample Buttock Marking 
 

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12.3. 
Digital Photography during Treatment Visits 1, 2, and 3 
During each treatment visit, each of the two buttocks will be photographed before and after 
marking dimples and injections sites while the subject is standing in a consistent, standardized 
relaxed pose as described in section 13.1.1. 
12.4. 
Treatment Visit 1 (Day 1) 
12.4.1. 
Treatment Visit 1: Pre-Injection 
1. Confirm eligibility criteria 
2. Take digital photography of each of the buttocks before marking dimples and injection 
sites (section 13.1.1) 
3. Subjects will get instruction on the use of the PR-PCSS (Patient Instructions for Use of 
PR-PCSS) 
4. Subjects will rate each of their buttocks using the PR-PCSS (section 13.1.2.1); the 
Investigator is blinded to these scores 
5. The Investigator will conduct live assessments of subject’s cellulite severity of each of 
the buttocks using the CR-PCSS (section 13.1.2.4); the subject is blinded to these ratings 
6. The Investigator will conduct live cellulite evaluation of each of the buttocks using the 
Hexsel CSS. The ratings from the PR-PCSS, CR-PCSS and Hexsel CSS 
(section 13.1.2.6) will be used to assess eligibility for randomization 
7. Subjects with PR-PCSS or CR-PCSS ratings in either of the buttocks <3 or a Hexsel CSS 
total score in either of the buttocks greater than 13 (section 13.1.2.6) will be excluded 
from participation 
8. Randomization of subjects with two buttocks eligible for treatment (eligible criteria being 
each buttock have PR-PCSS and CR-PCSS scores of 3 or 4 and a Hexsel CSS total score 
not greater than 13) to treatment (section 12.10); obtain kit numbers of study treatment 
9. Record concomitant medications/procedures (section 12.8) 
10. Vital sign measurements (section 14.9) 
11. Collection of samples for: 
a. Anti-AUX-I and anti-AUX-II antibody testing (section 14.8) 
b. Urine pregnancy testing (section 14.7) 
12. Select and mark dimples to be treated in each of the buttocks (section 12.2) 
13. Take digital photograph of each of the buttocks after marking dimples and injection sites 
(section 13.1.1) 
12.4.2. 
Treatment Visit 1: Injection and Post-injection 
1. Administration of study drug in the prone position (section 10.3) 

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2. Record number of dimples treated and number of injections administered in each of the 
two buttocks 
3. Vital sign measurements (section 14.9) 
4. Injection site reactions and local tolerability 
5. Adverse events (section 14) 
12.5. 
Treatment Visit 2 (Day 22 [±3 days]) and Treatment Visit 3 (Day 43 
[±3 days]) 
12.5.1. 
Treatment Visits 2 and 3: Pre-injection 
1. Record concomitant medications/procedures (section 12.8) 
2. Body weight measurements 
3. Vital sign measurements (section 14.9) 
4. Collection of samples for: 
a. Anti-AUX-I and anti-AUX-II antibody testing (section 14.8) 
b. Urine pregnancy testing (section 14.7) 
5. Digital photographs of each of the two buttocks before marking dimples and injection 
sites (section 13.1.1) 
6. Subject Cellulite Assessments of each of the buttocks using the photographic image of 
each buttock before marking dimples and injection sites (NOTE: complete subject 
cellulite assessments before Investigator cellulite assessments) in the following sequential 
order using: 
a. Patient Reported Photonumeric Cellulite Severity Scale (PR-PCSS) assessment 
(section 13.1.2.1); complete this prior to conducting S-GAIS  
b. Subject Global Aesthetic Improvement Scale (S-GAIS) (section 13.1.2.2) 
7. Investigator Cellulite Assessments live of each of the buttocks in the following sequential 
order prior to marking dimples and injection sites using: 
a. Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) live assessment 
of subject (section 13.1.2.4) 
b. Investigator Global Aesthetic Improvement Scale (I-GAIS) (section 13.1.2.5) 
8. Select and mark dimples to be treated in each buttock (section 12.2) 
9. Digital photographs of each buttock after marking dimples and injection sites 
(section 13.1.1)  
10. For eligible buttock(s), obtain kit number(s) of study treatment 
12.5.2. 
Treatment Visits 2 and 3: Injection and Post-injection 
1. Administration of study drug in the prone position (section 10.3) 
2. Record number of dimples treated and number of injections administered in each buttock 

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3. Vital sign measurements (section 14.9) 
4. Injection site reactions and local tolerability 
5. Adverse events (section 14) 
12.6. 
Day 71 (+5 days) End of Study / Early Termination 
The following procedures will be performed on Day 71: 
1. Record concomitant medications/procedures (section 12.8) 
2. Measurement of body weight 
3. Vital sign measurements (section 14.9) 
4. Collection of samples for: 
a. Clinical laboratory testing (section 14.7) 
b. Serum pregnancy test (section 14.7) 
c. Anti-AUX-I and anti-AUX-II antibody testing (section 14.8) 
5. Digital photographs of each of the buttocks 
6. Subject Cellulite Assessment of each of the two buttocks using the photographic image 
before marking dimples and injection sites (NOTE: complete subject cellulite 
assessments before Investigator cellulite assessments) using: 
a. Patient Reported Photonumeric Cellulite Severity Scale (PR-PCSS) assessment 
(section 13.1.2.1) 
b. Subject Global Aesthetic Improvement Scale (S-GAIS) (section 13.1.2.2) 
c. Subject Satisfaction with Cellulite Treatment Assessment (section 13.1.2.3); note this 
assessment is of both left and right buttocks rather than each individual buttock 
7. Investigator Cellulite Assessments of each of the buttocks live using: 
a. Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) live assessment 
of subject (section 13.1.2.4) 
b. Investigator Global Aesthetic Improvement Scale (I-GAIS) (section 13.1.2.5) 
8. Injection site reactions and local tolerability 
9. Adverse events (section 14) 
12.7. 
Unscheduled Visits 
If any subject needs to return to the site prior to her next scheduled visit, site staff should follow 
the Unscheduled Visit procedures outlined in section 5. Site staff may conduct additional study 
procedures if required. 
12.8. 
Prior and Concomitant Medications and Procedures 
All prior medications taken within 90 days before randomization will be recorded. All 
medications (including over-the-counter medications) taken by the subject on Day 1 through the 

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end of the study must be recorded. Any prior treatments (medications or procedures) for EFP 
through the end of the study must be recorded on the appropriate eCRF page. 
Additionally, any diagnostic, therapeutic or surgical procedures performed during the study 
period should be recorded including the date, indication for and description of the procedure. 
12.8.1. 
Prohibited Medications or Procedures 
The following medications are prohibited for randomized subjects during the study: 
anticoagulants (warfarin, heparin, direct thrombin inhibitors, Factor X inhibitors) and antiplatelet 
agents (aspirin >150 mg/day and P2Y12 inhibitors, such as clopidogrel), which can cause 
additional bruising. However the use of aspirin at a dose level of ≤150 mg per day will be 
permitted during study. 
Procedures listed in exclusion criterion #4 (section 11.2, Exclusion Criterion #4) are prohibited 
for randomized subjects during the study. 
Table 4: 
Concomitant Medication Restrictions for Subjects during the Treatment 
Phase of Study 
Drug Class 
Restrictions 
Anticoagulants 
Subjects cannot take antiplatelet agents or anticoagulants (except for 
≤150 mg aspirin daily) within 7 days before and 7 days after the dosing 
administration. 
12.9. 
Treatment Compliance 
Randomized subjects will receive study drug administered by an Investigator at the 
Investigator’s site. 
Accidental or intentional overdoses should be reported to the Sponsor/designee promptly (see 
section 14.6.2.1, Overdose). 
12.10. 
Blinding and Randomization 
On Day 1, if each of the buttocks again meet the criteria (3 or 4 on the PR-PCSS and CR-PCSS 
and no greater than 13 on Hexsel CSS) the subject will be randomized to a treatment group. The 
interactive web response system (IWRS) will randomly assign each subject to a treatment group 
(EN3835 0.84 mg per buttock × two buttocks or placebo) in a 1:1 ratio within an investigational 
site. The treatment group will remain blinded to the Investigator, subjects, all site personnel, and 
the sponsor. The IWRS will assign the subject study drug kit numbers associated with the 
randomized treatment. At Day 22 and 43 visits, the IWRS will again assign the subject study 
drug kit numbers associated with the randomized treatment assigned at Day 1. 
All precautions will be taken to ensure that the blinding of EN3835 and placebo is maintained 
throughout the study period. Unblinding will not be permitted by the study site unless it is 
deemed necessary for treatment of a medical emergency. Before breaking the blind, the 
Investigator should make every attempt to contact the Medical Monitor to discuss the necessity 
of breaking the blind. The study site will have the ability to immediately determine treatment 
identification in the event of an emergency by using the unblinding function within the IWRS, 
however, the Medical Monitor must be notified immediately. The Investigator will be required to 

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make a full written explanation of the reason for unblinding the subject and the date. In the event 
that a subject is unblinded prior to contacting the Medical Monitor, the Investigator must provide 
this information in writing to the Medical Monitor as soon as possible. Breaking the blind at the 
investigative site will immediately disqualify the subject from further participation in the study. 
In addition, the event(s) leading to emergency unblinding must be reported as an SAE according 
to instructions in section 14.5.2, Reporting Serious Adverse Events. 
In addition, it may be necessary for the Investigator or qualified designee to unblind a subject as 
a result of a clinically significant finding noted during safety review by the Investigator, Safety 
Monitor, Medical Monitor and/or qualified designee that might jeopardize subject safety. 
 

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13. 
ASSESSMENT OF EFFICACY 
13.1. 
Efficacy Measurements 
13.1.1. 
Digital Photography  
Although digital photographs are not direct efficacy measurements, digital photography will be 
utilized in the assessment of certain efficacy measurements ie to assess certain cellulite severity 
parameters at specific intervals (see section 5, Schedule of Events). At the Screening visit, the 
Investigator or qualified designee will photograph each buttock using a Sponsor-supplied 
standardized digital camera in a standardized manner. The subject will be standing for each 
photography session and will be wearing a standardized photographic garment as described in 
the Photography Manual. The Investigator or qualified designee will photograph each of the two 
buttocks while the subject is standing in a consistent, standardized relaxed standing pose, 
ie, standing position with relaxed gluteus muscles, at the following time points: 
 Screening (no markings of dimples or injection site) - each of the two buttocks 
 Before and after marking dimples and injection sites (prior to injections) on Days 1, 
22, and 43 - each of the two buttocks 
 During the Day 71 visit (end of study/early termination) (no dimple or injection site 
markings) - each of the two buttocks 
All photographs from this study are the property of Endo and may be utilized for clinical 
development, scientific communication, marketing, regulatory purposes, and/or legal 
applications as required/desired by Endo. 
13.1.2. 
Subject and Investigator Cellulite Assessments 
Investigator cellulite assessments are independent of the subject assessments. Therefore, all 
subject cellulite assessments must be completed before the Investigator’s cellulite assessments 
are initiated. The subject assessments will be done using a subject-assigned password protected 
electronic patient reported outcome (ePRO) system and the Investigator and study site personnel 
will not have access to the subject’s assessments or password; the clinician assessment will be 
recorded in an investigator-assigned password protected system and the subject will not have 
access to the Investigator’s assessments or password. Subject assessments will be done alone 
with no study site personnel in the room. Investigators will be instructed not to verbalize their 
ratings while in the presence of the subject. 
13.1.2.1. Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) 
The PR-PCSS will be conducted for the purpose of assessing the severity of cellulite in the 
buttock. The scale is a 5-level photonumeric scale developed specifically for patients and used 
by the subject to assess the severity of their cellulite in the buttocks by viewing digital images of 
each of their buttocks captured by photography at the visit; the ratings range from 0 (None) to 
4 (Severe) with labels and descriptors to aid the subject in the assessments.  

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At Screening and at the beginning of their visits on Day 1, Day 22, Day 43, and Day 71, subjects 
will have digital photographs taken of each of their two buttocks. Subjects will be given 
instructions in the proper use (Patient Instructions for Use of PR-PCSS) of the PR-PCSS and 
then perform the PR-PCSS for each of the buttocks (Appendix B). While viewing the digital 
images of each of their buttocks on a standardized computer monitor and using PR-PCSS for 
buttock, subjects will be instructed to answer the following question for each buttock: Today, 
how would you rate the severity of your cellulite in the area displayed using the PR-PCSS? The 
subject will be given the following explanations: Please try to match the severity of your 
cellulite, as seen in this digital image, with one of the cellulite levels on the PR-PCSS. Please 
look at the image of your cellulite and the pictures, labels, and descriptions on the PR-PCSS 
carefully before selecting your answer. If you feel that your cellulite level is between 2 of the 
levels, please select the level that is closest to your image. If you feel that your cellulite is exactly 
halfway between two PR-PCSS levels of cellulite severity, please select the more severe 
response. 
The subject will enter their rating electronically into an ePRO system; the Investigator and other 
site personnel will be blinded to the rating entered by the subject. This variable will be entered 
directly into the EDC system, thus the electronic database will serve as the direct point of data 
capture and will serve as source for this variable. 
13.1.2.2. Subject Global Aesthetic Improvement Scale (S-GAIS) 
Subjects will complete the S-GAIS for each of the buttocks as described below at the Day 22, 
Day 43, and Day 71 study visits using the pre-treatment Day 1 digital image (Baseline) of each 
of the buttocks for comparison. 
All treated subjects will be instructed to answer the following question for each buttock:  
How would you rate the appearance of your treated cellulite after treatment? 
The S-GAIS assessment will occur after the subject has completed the PR-PCSS assessment to 
avoid introducing potential bias to the static PR-PCSS assessment. The subject will view each of 
their pre-treatment Day 1 digital images alongside their Day 22, Day 43 or Day 71/End of study 
visit digital images of each of their buttocks to aid in the assessment (Table 5). Subjects will 
provide a rating from those below that best represents their answer for each treated buttock. 
This variable will be entered directly into the EDC system, thus the electronic database will serve 
as the direct point of data capture and will serve as source for this variable. 
Table 5: 
Subject Global Aesthetic Improvement Scale (S-GAIS) 
Rating 
Response Option 
Description 
+3 
Very much improved 
My treated cellulite looks very much better. 
+2 
Much improved 
My treated cellulite looks much better, but additional treatment 
would slightly improve the result. 
+1 
Improved 
My treated cellulite looks better, but additional treatment is 
necessary. 
0 
No change 
My treated cellulite looks essentially the same as it did 
originally. 

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Table 5: 
Subject Global Aesthetic Improvement Scale (S-GAIS) (Continued) 
Rating 
Response Option 
Description 
−1 
Worse 
My treated cellulite looks worse than it did originally. 
−2 
Much worse 
My treated cellulite looks much worse than it did originally. 
−3 
Very much worse 
My treated cellulite looks very much worse than it did 
originally. 
13.1.2.3. Subject Satisfaction with Cellulite Treatment Assessment 
At the Day 71 visit, subjects will be instructed to answer a question related to their treated 
buttocks. Subjects will be given a list of responses and they will provide a rating from those 
below that best represents their answer (Table 6). 
Today, how satisfied are you with the results of the cellulite treatment you received on the 
specific area or areas on your buttocks that were treated? 
Table 6: 
Subject Satisfaction with Cellulite Treatment Assessment - Buttocks 
Rating 
Description 
+2 
I am very satisfied with the cellulite treatment on my buttocks. 
+1 
I am satisfied with the cellulite treatment on my buttocks. 
0 
I am neither dissatisfied nor satisfied with the cellulite treatment on my buttocks. 
-1 
I am dissatisfied with the cellulite treatment on my buttocks. 
-2 
I am very dissatisfied with the cellulite treatment on my buttocks. 
13.1.2.4. Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 
The CR-PCSS will be conducted for the purpose of assessing the severity of cellulite in the 
buttock. The scale is a 5-level photonumeric scale developed specifically for clinicians and used 
by the Investigator to assess the severity of the subject’s cellulite in each buttock by live 
assessments; the ratings range from 0 (None) to 4 (Severe) with labels and descriptors to aid the 
Investigator in the assessments. 
Investigators will be trained and qualified on the use of the CR-PCSS prior to assessing any 
subjects. 
At the Screening visit, the Investigator will determine severity of cellulite of each of the 
two buttocks via live assessment of the subject using the CR-PCSS for buttock (Appendix C) 
after the subject has completed her self-assessment using the PR-PCSS. Before injections on 
treatment visits Day 1, Day 22, and Day 43, and on visit Day 71; Investigators will evaluate each 
of the two buttocks by live assessments using the CR-PCSS for the buttock to make his/her 
evaluation. At each visit, the Investigator will make his/her assessment independently and after 
the subject has conducted her self-assessment using the PR-PCSS. 
This variable will be entered directly into the EDC system, thus the electronic database will serve 
as the direct point of data capture and will serve as source for this variable. 

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13.1.2.5. Investigator Global Aesthetic Improvement Scale (I-GAIS) 
On the Day 22, Day 43, and Day 71 study visits, the Investigator will determine the degree of 
improvement of each buttock by comparing the cellulite from the Day 1 pre-treatment (Baseline) 
digital image of each buttock to the cellulite seen in a live assessment (Table 7). The I-GAIS 
assessment will occur after the CR-PCSS assessment (section 13.1.2.4) to avoid introducing 
potential bias to the static CR-PCSS assessment by the Investigator. For each buttock, the 
Investigator will provide the rating from those below that best represents his/her answer. 
This variable will be entered directly into the EDC system, thus the electronic database will serve 
as the direct point of data capture and will serve as source for this variable. 
Table 7: 
Investigator Global Aesthetic Improvement Scale (I-GAIS) 
Rating 
Response Option 
Description 
+3 
Very much improved 
Optimal cosmetic result from treatment of the treated dimples 
+2 
Much improved 
Marked improvement in the treated area appearance from 
before treatment, but not completely optimal 
+1 
Improved 
Obvious improvement in the treated area appearance from 
before treatment, but additional treatment is indicated 
0 
No change 
The treated area appearance is essentially the same as before 
treatment 
−1 
Worse 
The treated area appearance is worse than before treatment 
−2 
Much worse 
Marked worsening in appearance from the initial condition 
−3 
Very much worse 
Obvious worsening in appearance from the initial condition 
13.1.2.6. Hexsel Cellulite Severity Scale 
The Hexsel Cellulite Severity Scale (referred to as the Hexsel CSS) is a photonumeric scale that 
looks at 5 key morphologic features of cellulite: (A) number of evident depressions, (B) depth of 
depressions, (C) morphological appearance of skin surface alterations, (D) laxity, flaccidity or 
sagging of skin, and (E) current classification scale based on medical literature including 
Nürnberger and Müller.(12,13) Each of these features is evaluated on a 4-point scale from a low 
of 0 to a high of 3 as described in Table 8. The total score is the summation of all 5 features 
(Appendix D). 
The Investigator or qualified designee will independently use the Hexsel CSS to assess the 
severity of EFP in each of the two buttocks at the Screening visit and each of the two buttocks on 
Day 1 (Note: In this study, the Hexsel CSS is used exclusively for assessment of subject 
eligibility; it is not used as an efficacy assessment). All cellulite assessments should be made 
while the subject is in the standing position with relaxed gluteus muscles. However, when 
evaluating the subject for Category E (classification scale by Nürnberger and Müller) (13) if the 
subject has no evident depressions, the subject should be asked to contract her gluteus muscles or 
the pinch test should be applied (by pinching the skin between the thumb and index finger) so the 
Investigator or qualified designee can differentiate between scores/grades of zero (0) or I. 
This variable will be entered directly into the EDC system, thus the electronic database will serve 
as the direct point of data capture and will serve as source for this variable. 

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Table 8: 
Hexsel Cellulite Severity Scale 
A 
Number of evident depressions 
0=none/no depressions 
1=a small amount: 1-4 depressions are visible 
2=a moderate amount: 5-9 depressions are visible 
3=a large amount: 10 or more depressions are visible 
B 
Depth of depressions 
0=no depressions 
1=superficial depressions 
2=medium depth depressions 
3=deep depressions 
C 
Morphological appearance of skin 
surface alterations 
0=no raised areas 
1=‘orange peel’ appearance 
2=‘cottage cheese’ appearance 
3=‘mattress’ appearance 
D 
Grade of laxity, flaccidity, or sagging 
skin 
0=absence of laxity, flaccidity, or sagging skin 
1=slight draped appearance 
2=moderate draped appearance 
3=severe draped appearance 
E 
Classification scale by Nürnberger and 
Müllera 
0 = zero grade = Grade or Stage 0 = There is no alteration of the 
skin surface. 
1 = first grade = Grade or Stage I = The skin of the affected area 
is smooth while the subject is standing or lying, but the 
alterations to the skin surface can be seen by pinching the skin 
or with muscle contraction. 
2= second grade = Grade or Stage II = The orange skin or 
mattress appearance is evident when standing, without the use 
of any manipulation (skin pinching or muscle contraction). 
3= third grade = Grade or Stage III = The alterations described 
in Grade or Stage II, are present together with raised areas and 
nodules. 
a Subjects should be evaluated in the standing position with relaxed gluteus muscles. However, if the subject has no 
evident depressions, they should be asked to contract their gluteus muscles or the pinch test should be applied (by 
pinching the skin between the thumb and index finger) in order to differentiate between grade/stage of zero (0)  
or I. 
Source: Hexsel DM, Dal’Forno T, Hexsel CL. A validated photonumeric cellulite severity scale. J Eur Acad 
Dermatol Venereol. 2009;23(5):523-8. 

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14. 
ASSESSMENT OF SAFETY 
14.1. 
Definitions 
14.1.1. 
Adverse Events 
An adverse event (AE) is any unfavorable or unintended change in body structure (signs), body 
function (symptoms), laboratory result (eg, chemistry, ECG, X-ray, etc), or worsening of a 
pre-existing condition associated temporally with the use of the study medication whether or not 
considered related to the study medication. Adverse events will be captured once a subject has 
signed the informed consent. AEs include: 
 Changes in the general condition of the subject 
 Subjective symptoms offered by or elicited from the subject 
 Objective signs observed by the Investigator or other study personnel 
 All concurrent diseases that occur after the start of the study, including any change in 
severity or frequency of pre-existing disease 
 All clinically relevant laboratory abnormalities or physical findings that occur during 
the study 
A treatment-emergent adverse event (TEAE) is any condition that was not present prior to 
treatment with study medication but appeared following treatment, was present at treatment 
initiation but worsened during treatment, or was present at treatment initiation but resolved and 
then reappeared while the individual was on treatment (regardless of the intensity of the AE 
when the treatment was initiated). 
All AEs, including both observed or volunteered problems, complaints, signs or symptoms must 
be recorded on the AE page of the eCRF, regardless of whether associated with the use of study 
medication. This would include AEs resulting from concurrent illness, reactions to concurrent 
medication use, or progression of disease states (excluding the disease under study). A condition 
present at baseline that worsens after initiation of study treatment will be captured as an AE; the 
onset date will be the date the event worsened. The AE should be recorded in standard medical 
terminology when possible. 
14.1.2. 
Serious Adverse Events 
A serious adverse event (SAE) is defined as an AE that: 
 Results in death 
 Is immediately life-threatening (there is an immediate risk of death from the AE as it 
occurred; this does not include an AE that had it occurred in a more serious form may 
have caused death) 
 Results in or prolongs an inpatient hospitalization (Note: a hospitalization for elective 
or pre-planned surgery, procedure, or drug therapy does not constitute an SAE) 

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 Results in permanent or substantial disability (permanent or substantial disruption of 
one’s ability to conduct normal life functions) 
 Is a congenital anomaly/birth defect (in offspring of a subject using the study 
medication regardless of time to diagnosis) 
 Is considered an important medical event 
Important medical events are defined as events that, based upon appropriate medical judgment, 
may jeopardize the subject and may require medical or surgical intervention to prevent one of the 
other serious outcomes. Examples of important medical events include malignancy, allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias 
or convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
14.2. 
Monitoring Adverse Events 
At each visit, subjects will be queried regarding any AEs that have occurred since the last visit. 
Subjects will be asked to volunteer information concerning AEs with a non-leading question 
such as, “How do you feel?” Study site personnel will then record all pertinent information in the 
source documents and the eCRF. The study drug compliance record should also be reviewed to 
detect potential overdoses (intentional/unintentional). 
14.3. 
Relationship to Study Drug 
The degree of “relatedness” of the AE to the study medication must be described using the 
following scale: 
 Not related indicates that the AE is definitely not related to the study medication. 
 Unlikely related indicates that there are other, more likely causes and study 
medication is not suspected as a cause. 
 Possibly related indicates that a direct cause and effect relationship between study 
medication and the AE has not been demonstrated, but there is evidence to suggest 
there is a reasonable possibility that the event was caused by the study medication. 
 Probably related indicates that there is evidence suggesting a direct cause and effect 
relationship between the AE and the study medication. 
It is the Sponsor’s policy to consider “Probably related” and “Possibly related” causality 
assessments as positive causality. “Not related” and “Unlikely related” causality assessments are 
considered as negative causality. 
Assessments will be recorded on the eCRF and must indicate clearly the relationship being 
assessed. For example, an AE that appears during a placebo run-in phase would be assessed with 
respect to the placebo treatment received and/or study procedures conducted during this phase. If 
the AE continued into an active treatment phase, the relationship would be assessed for the active 
treatment phase only if the AE worsened. 

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14.4. 
Intensity Assessment 
The intensity (or severity) of AEs is characterized as mild, moderate, or severe: 
 Mild AEs are usually transient, requiring no special treatment, and do not interfere 
with the subject’s daily activities. 
 Moderate AEs introduce a low level of inconvenience or concern to the subject and 
may interfere with daily activities, but are usually ameliorated by simple therapeutic 
measures. 
 Severe AEs interrupt a subject’s usual daily activity and typically require systemic 
drug therapy or other treatment. 
When the intensity category of an AE changes, the greatest intensity during that continuous 
episode should be recorded. 
14.5. 
Reporting Adverse Events and Serious Adverse Events 
14.5.1. 
Reporting Adverse Events 
Throughout the study, AEs will be documented on the source document and on the appropriate 
page of the eCRF whether or not considered treatment-related. This includes any new signs, 
symptoms, injury or illness, including increased severity of previously existing signs, symptoms, 
injury, or illness. Conditions existing prior to screening will be recorded as part of the subject’s 
medical history. The Investigator is responsible for assessing the relationship of AEs to the study 
medication; relationship will be classified as not related, unlikely related, possibly related, or 
probably related. 
All AEs will be collected by the Investigator from the time of signing the informed consent 
through 28 days after the last dose of study medication; this includes any AEs that are ongoing at 
the time of completion/termination of the study. All ongoing AEs must be followed until 
resolution or for 30 days after the subject’s last study visit, whichever comes first. 
14.5.2. 
Reporting Serious Adverse Events 
Any SAE, including death resulting from any cause, which occurs to any subject participating in 
this study must be reported via email or fax by the Investigator using the Endo Clinical Trial 
Report Form for SAEs within 24 hours of first becoming aware of the SAE. SAEs will be 
collected by the Investigator from the time of signing the informed consent through 28 days after 
the last dose of study medication. SAEs that occur within 28 days, following cessation of the 
study treatment, or within 30 days, following premature discontinuation from the study for any 
reason, must also be reported within the same timeframe. Any SAE that is felt by the Investigator 
to be related to the study medication must be reported regardless of the amount of time since the 
last dose received. Follow-up information collected for any initial report of an SAE must also be 
reported to the Sponsor within 24 hours of receipt by the Investigator. 
All SAEs will be followed until resolution, stabilization of condition, or until follow-up is no 
longer possible. 

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In the event discussion is necessary regarding treatment of a subject, call the Medical 
Monitor (see contact information in section 3). 
All SAEs should be sent via the email address, or faxed to the fax number, provided in 
section 3. 
The Sponsor will determine whether the SAE must be reported within 7 or 15 days to regulatory 
authorities in compliance with local and regional law. If so, the Sponsor (or the Sponsor’s 
representative) will report the event to the appropriate regulatory authorities. The Investigator 
will report SAEs to the IRB per their IRB policy. 
14.5.2.1. Follow-up Procedures for Serious Adverse Events 
To fully understand the nature of any SAE, obtaining follow-up information is important. 
Whenever possible, relevant medical records such as discharge summaries, medical 
consultations, and the like should be obtained. In the event of death, regardless of cause, all 
attempts should be made to obtain the death certificate and any autopsy report. These records 
should be reviewed in detail, and the Investigator should comment on any event, lab 
abnormality, or any other finding, noting whether it should be considered a serious or 
non-serious AE, or whether it should be considered as part of the subject’s history. In addition, 
all events or other findings determined to be SAEs should be identified on the follow-up SAE 
form and the Investigator should consider whether the event is related or not related to study 
drug. 
14.6. 
Special Reporting Situations 
14.6.1. 
Adverse Events of Special Interest 
Adverse events such as bruising, ecchymosis, hematomas, and contusions that occur remote to 
the site of drug administration, or any hypersensitivity reactions, including anaphylaxis, will be 
recorded as an AE or SAE as appropriate (see section 14.1.1, Adverse Events or section 14.1.2, 
Serious Adverse Events). 
14.6.2. 
Overdose/Misuse/Abuse 
14.6.2.1. Overdose 
Study drug overdose is any accidental or intentional use of study drug in an amount higher than 
the dose indicated by the protocol for that subject. Study drug compliance (see section 12.9) 
should be reviewed to detect potential instances of overdose (intentional or accidental). 
Any study drug overdose during the study should be noted on the study medication eCRF. 
An overdose is not an AE per se, however all AEs associated with an overdose should both be 
entered on the Adverse Event eCRF and reported using the procedures detailed in section 14.5.2, 
Reporting of Serious Adverse Events, even if the events do not meet seriousness criteria. If the 
AE associated with an overdose does not meet seriousness criteria, it must still be reported using 
the Endo Clinical Trial Report Form for SAEs and in an expedited manner, but should be noted 
as non-serious on the form and the Adverse Event eCRF. 

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14.6.3. 
Pregnancy 
Subjects should be instructed to immediately notify the Investigator of any pregnancies. 
Any pregnancy that occurs in a subject during this clinical study will be reported for tracking 
purposes only. All subject pregnancies that are identified during or after this study, where the 
estimated date of conception is determined to have occurred during study drug therapy or within 
28 days of the last dose of study medication need to be reported, followed to conclusion, and the 
outcome reported, even if the subject is discontinued from the study. The Investigator should 
report all pregnancies within 24 hours using the Initial Pregnancy Report Form, and any 
pregnancy-associated SAE using the SAE report form, according to the usual timelines and 
directions for SAE reporting provided in section 14.5.2. Monitoring of the pregnancy should 
continue until conclusion of the pregnancy; 1 or more Follow-up Pregnancy Report Form(s) 
detailing progress, and a Two Month Follow-up Pregnancy Report Form detailing the outcome, 
should be submitted. 
Pregnancy itself is not regarded as an AE unless there is suspicion that the investigational 
product under study may have interfered with the effectiveness of a contraceptive medication. 
Likewise, elective abortions without complications are not considered AEs. Any SAEs 
associated with pregnancy (eg, congenital abnormalities/birth defects/spontaneous miscarriages 
or any other serious events) must additionally be reported as such using the SAE report form. 
Spontaneous miscarriages should also be reported and handled as SAEs. 
A subject who becomes pregnant must be withdrawn from the study. Attempts to obtain the 
pregnancy follow-up and pregnancy outcome information detailed above are necessary even if a 
subject discontinues treatment because of pregnancy. 
14.6.4. 
AEs/SAEs Experienced by Non-subjects Exposed to Study Medication 
Non-subjects are persons who are not enrolled in the study but have been exposed to study 
medication, including instances of diversion of study medication. All such AEs/SAEs occurring 
in non-subjects from such exposure will be reported to the Endo PVRM Department (when the 
non-subject agrees) on the departmental form for serious adverse experiences regardless of 
whether the event is serious or not. Instructions for completing the form for events experienced 
by non-subjects will be provided. SAEs occurring in non-subjects exposed to study medication 
will be processed within the same SAE reporting timelines as described in section 14.5.2, 
Reporting Serious Adverse Events. Additionally, the drug accountability source documentation 
at the site should reflect this occurrence. 
14.7. 
Clinical Laboratory Determinations 
Clinical laboratory tests will be conducted according to the Schedule of Events (section 5). 
Clinical laboratory tests will be performed by a designated central laboratory. Each site will be 
provided with instructions on specimen collection, preparation, packaging and transport. Refer to 
the central laboratory manual for further information regarding sample collection, handling, and 
labeling. The results of the tests will be returned to the investigational sites.  

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Clinical laboratory test data will be reviewed by the Investigator, or designee, and additional 
clinical laboratory tests may be ordered at his/her discretion (eg, if the results of any clinical 
laboratory test falls outside the reference range or clinical symptoms necessitate additional 
testing to ensure safety). Any additional testing will be performed by the designated central 
laboratory. The Investigator or qualified designee must acknowledge the review of laboratory 
results. 
The Investigator will review all abnormal lab results for potentially clinically important. Any 
abnormal clinical laboratory test result meeting the Investigator’s criteria for potentially 
clinically important (refer to central laboratory manual) will be recorded as an AE or SAE as 
appropriate (see section 14.1.1, Adverse Events, and section 14.1.2, Serious Adverse Events). 
Laboratory results will be sent electronically to Endo Pharmaceuticals Inc. for data management. 
Clinical laboratory parameters that will be measured in this study are listed in Table 9. 
Table 9: 
Clinical Laboratory Tests 
Hematology 
Biochemistry 
Urinalysis 
Hemoglobin 
Glucose 
Glucose 
Hematocrit 
Sodium 
Protein 
Red blood cell 
Potassium 
Specific gravity 
White blood cell (WBC) 
Calcium 
pH 
Platelets 
Chloride 
Ketones 
WBC Differential 
CO2 
Bilirubin 
 
Inorganic phosphate 
Urobilinogen 
 
Blood urea nitrogen  
Nitrite 
 
Creatinine 
Blood* 
 
Creatinine clearance (estimated)  
Leukocytes* 
 
Aspartate transaminase (AST) 
 
 
Alanine transaminase (ALT) 
 
 
Gamma-glutamyl transferase (GGT) 
 
 
Total bilirubin (TBL) (direct bilirubin reflex if elevated) 
 
 
Albumin 
 
 
Alkaline phosphatase (ALP) 
 
 
Uric acid 
 
* Microscopic examination will be performed if blood or leukocytes are detected by dipstick. 
For women of childbearing potential, a serum pregnancy test will be performed at Screening and 
Day 71/End of Study/Early Termination, and urine pregnancy tests will be performed at Day 1, 
Day 22, and Day 43 (refer to section 5). Female subjects of childbearing potential must have a 
negative pregnancy test at the Screening Visit and at Day 1 (Baseline), Day 22, and Day 43 to be 
randomized and/or receive treatment in the study. If necessary, additional urine pregnancy tests 
can be performed at any time during the study at the discretion of the Investigator. Urine 
pregnancy test kits will be supplied by the Sponsor. 

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14.11. 
Physical Examination 
A complete physical examination will be performed at the Screening Visit. All examinations will 
be performed by a physician or health professional listed on the Form FDA 1572 and licensed to 
perform physical examinations. Height and body weight will be measured and recorded at 
screening. 
The Investigator will review all physical exam findings for clinical significance. Any physical 
exam finding meeting the Investigator’s or Sponsor’s criteria for clinical significance will be 
recorded as an AE or SAE as appropriate (see section 14.1.1, Adverse Events and section 14.1.2, 
Serious Adverse Events). 
At screening, the Investigator will also assess the subject’s skin type using the Fitzpatrick scale 
(Table 11). Only the Fitzpatrick Scale shown below may be used during the study. 
Table 11: 
Fitzpatrick Scale 
I 
Pale white skin, blue/hazel eyes, blond/red hair 
Always burns, does not tan 
II 
Fair skin, blue eyes 
Burns easily, tans poorly 
III 
Darker white skin 
Tans after initial burn 
IV 
Light brown skin 
Burns minimally, tans easily 
V 
Brown skin 
Rarely burns, tans darkly easily 
VI 
Dark brown or black skin 
Never burns, always tans darkly 
Follow-up body weight will be measured before injection on Day 22 and Day 43 and at the 
Day 71 visit. 
14.12. 
Other Safety Assessments 
Not applicable. 

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15. 
ASSESSMENT OF PHARMACOKINETICS 
Not applicable. 

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16. 
ASSESSMENT OF PHARMACODYNAMICS 
Not applicable. 

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17.2.2. 
Intent-to-Treat (ITT) Population 
The ITT population is defined as all randomized subjects who have received at least one 
injection of study medication. All demographic and baseline characteristic summaries will be 
based on this population. The primary and key secondary efficacy parameters will be 
summarized based on this population. 
17.2.3. 
Modified Intent-to-Treat (mITT) Population 
The mITT population is defined as all intent-to-treat subjects with a baseline and at least 1 
post-injection evaluation of both the Investigator CR-PCSS and subject PR-PCSS for both left 
and right buttocks. All secondary and supportive efficacy evaluations will be based on the mITT 
population. 
17.2.4. 
Per-Protocol (PP) Population 
The per-protocol population is defined as the mITT subjects without any major protocol 
deviation that will impact the subject’s efficacy and safety. This population may be used in the 
efficacy sensitivity analysis. 
17.3. 
Subject Disposition 
The number of subjects included in each study population will be summarized by treatment 
group. Subjects excluded from the safety and efficacy (eg, ITT) populations will be listed by 
treatment group. 
The number and percentage of subjects completed and prematurely discontinued during the 
treatment period will be presented for each treatment group and pooled across treatment groups. 
Screen failures (ie, screened but not randomized subjects) and the associated failure reasons will 
be tabulated overall. Reasons for premature discontinuation from the treatment period as 
recorded on the termination page of the eCRF will be summarized (number and percentage) by 
treatment group for all randomized subjects. Percentage of premature discontinuations will be 
compared between treatment groups. 
17.4. 
Demographics and Other Baseline Characteristics 
The summarization of demographic variables (eg, age, sex, race, weight, height, and body mass 
index [BMI]), medical and surgical history, and other baseline characteristics relevant to the 
indication studied in the study will be described. 
Demographic characteristics, including sex, age, age group, race, height, and weight, will be 
summarized by treatment group, for the ITT population, using descriptive statistics. All 
screening characteristics and medical information will also be summarized by treatment group 
using descriptive statistics. The descriptive summaries will include frequency tables for all 
categorical response variables and n, mean, standard deviation (SD), median, minimum and 
maximum for all continuous variables. 

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17.5. 
Efficacy Analyses 
All efficacy endpoints including supportive efficacy analysis will be summarized as percentages. 
The dichotomous secondary endpoints (ie, responder endpoints) will be analyzed using a 
Cochran-Mantel-Haenszel test adjusted for Investigator. Changes in the PR-PCSS ratings and 
CR-PCSS ratings from baselines, S-GAIS scores, and I-GAIS scores will be analyzed using the 
Wilcoxon rank sum test. All the tests are two-sided. 
The primary endpoint will be summarized as percentages and analyzed using a Cochran-Mantel-
Haenszel test that compares the 2 treatment groups and adjusts for Investigator at a level of 
significance of 0.05 based on the ITT population. Any subject who does not have an evaluation 
of CR-PCSS and/or PR-PCSS at Day 71 will be classified as a non-responder. 
The key secondary efficacy analyses will be analyzed in the same manner as the primary 
endpoint based on the ITT population. Any subject who does not have an evaluation at Day 71 
will be classified as a non-responder for the analyses. The family #1 key secondary efficacy 
analyses will be performed only if the primary efficacy analysis is significant (p ≤ 0.05; 
gatekeeping strategy). Similarly family #2 key secondary efficacy analyses will be performed 
only if at least one of the key secondary efficacy endpoints of family #1 is significant (p ≤ 0.025; 
parallel gatekeeping strategy). Within a family of key secondary efficacy endpoints, Bonferroni 
method will be performed to relocate unused alpha for testing each endpoint to assure an overall 
error rate of p ≤ 0.05. The details of the testing procedures will be provided in the statistical 
analysis plan for the study. 
All supportive endpoints will be summarized as percentages. All the supportive analyses will be 
performed based on all observed data (ie, missing data not imputed) in the mITT population at 
all visits without multiplicity adjustment. This analysis will also be performed at Day 71 with 
missing data at Day 71 imputed by a last observation carried forward (LOCF) approach if 
subjects have at least one post-dose assessment. The dichotomous secondary endpoints (ie, 
responder endpoints) will be analyzed using a Cochran-Mantel-Haenszel test adjusted for 
Investigator. Changes in the PR-PCSS ratings and CR-PCSS ratings from baselines, S-GAIS 
scores, and I-GAIS scores will be analyzed using the Wilcoxon rank sum test. 
17.5.1. 
Primary Efficacy Variable 
The primary efficacy variable is the proportion of 2-level composite responders at Day 71 
defined as subjects with at least one of two treated buttocks with: 
 an improvement in severity from baseline (Day 1 visit) of at least 2 levels of severity 
in the CR-PCSS as assessed live by the Investigator, and  
 an improvement in severity from baseline of at least 2 levels of severity in the 
PR-PCSS by the subject while viewing the digital image of the same buttock. 
A subject will be considered a responder if these criteria are met in either the left buttock or right 
buttock or both buttocks in that subject. In other words, a subject will be considered a responder 
if she has an improvement of at least 2 levels on the PR-PCSS and an improvement of at least 
2 levels on the CR-PCSS on that same buttock; that buttock could be the left buttock or right 
buttock or both buttocks. 

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Sensitivity analyses for the primary endpoint will include: 
 ITT subjects with missing data handled by multiple imputation (MI) approach 
 ITT subjects with missing data handled by an LOCF approach 
 mITT subjects with missing data handled by an LOCF approach 
 Observed data only (no missing data handling) 
 Per-protocol (PP) subjects with missing data handled by an LOCF approach if 10% or 
more subjects are excluded in the PP population from mITT population 
17.5.2. 
Secondary Efficacy Variables 
17.5.2.1. Key Secondary Variables 
There will be 4 key secondary endpoints grouped in two families of 2 endpoints per family 
analyzed in a hierarchical order. 
 Family #1 – two endpoints: 
 Proportion of 1-level PR-PCSS responders defined as subjects with ≥1-level 
improvement in PR-PCSS severity rating of left buttock at Day 71 compared to 
Day 1 
 Proportion of 1-level PR-PCSS responders defined as subjects with ≥1-level 
improvement in PR-PCSS severity rating of right buttock at Day 71 compared to 
Day 1 
 Family #2 – two endpoints: 
 Proportion of 1-level S-GAIS responders defined as subjects with ≥1-level 
improvement (improved, much improved or very much improved) in the S- GAIS 
assessment of left buttock at Day 71 
 Proportion of 1-level S-GAIS responders defined as subjects with ≥1-level 
improvement (improved, much improved or very much improved) in the S-GAIS 
assessment of right buttock at Day 71 
17.5.3. 
Supportive Efficacy Variables 
17.5.3.1. Supportive Variables 
The supportive variables will evaluate assessments at various study time points and using various 
populations. 
 Proportion of 2-level PR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 2 levels of severity in the PR-PCSS of the left 
buttock (Days 22, 43, and 71) 
 Proportion of 2-level PR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 2 levels of severity in the PR-PCSS of the right 
buttock (Days 22, 43, and 71) 

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 Proportion of 1-level PR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 1 level of severity in the PR-PCSS of left buttock 
(Days 22, 43, and 71) 
 Proportion of 1-level PR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 1 level of severity in the PR-PCSS of right 
buttock (Days 22, 43, and 71) 
 Proportion of 2-level PR-PCSS responders of at least one buttock (Days 22, 43, and 
71). A subject will be considered a responder if this criterion is met in the left buttock 
or right buttock or both buttocks in that subject. 
 Proportion of 1-level PR-PCSS responders of at least one buttock (Days 22, 43, and 
71). A subject will be considered a responder if this criterion is met in the left buttock 
or right buttock or both buttocks in that subject. 
 Proportion of 2-level PR-PCSS responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both left and right buttocks. 
 Proportion of 1-level PR-PCSS responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both left and right buttocks. 
 Proportion of 2-level CR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 2 levels of severity in the CR-PCSS of the left 
buttock (Days 22, 43, and 71) 
 Proportion of 2-level CR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 2 levels of severity in the CR-PCSS of the right 
buttock (Days 22, 43, and 71) 
 Proportion of 1-level CR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 1 level of severity in the CR-PCSS of the left 
buttock (Days 22, 43, and 71) 
 Proportion of 1-level CR-PCSS responders defined as subjects with an improvement 
in severity from baseline of at least 1 level of severity in the CR-PCSS of the right 
buttock (Days 22, 43, and 71) 
 Proportion of 2-level CR-PCSS responders of at least one buttock (Days 22, 43, and 
71). A subject will be considered a responder if this criterion is met in the left buttock 
or right buttock or both buttocks in that subject. 
 Proportion of 1-level CR-PCSS responders of at least one buttock (Days 22, 43, and 
71). A subject will be considered a responder if this criterion is met in the left buttock 
or right buttock or both buttocks in that subject. 
 Proportion of 2-level CR-PCSS responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both left and right buttocks. 

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 Proportion of 1-level CR-PCSS responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both left and right buttocks. 
 Proportion of 1-level composite responders of the left buttock (defined as subjects 
with an improvement in severity from baseline of at least 1 level of severity in the 
CR-PCSS of the left buttock assessed live by the Investigator and an improvement of 
severity from baseline of at least 1 level of severity in the PR-PCSS of that same left 
buttock) (Days 22, 43, and 71) 
 Proportion of 1-level composite responders of the right buttock (defined as subjects 
with an improvement in severity from baseline of at least 1 level of severity in the 
CR-PCSS of the right buttock assessed live by the Investigator and an improvement 
of severity from baseline of at least 1 level of severity in the PR-PCSS of that same 
right buttock) (Days 22, 43, and 71) 
 Proportion of 1-level composite responders of at least one buttock (Days 22, 43, and 
71). A subject will be considered a responder if this criterion is met in the left buttock 
or right buttock or both buttocks in that subject. 
 Proportion of 1-level composite responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both left and right buttocks. 
 Proportion of 2-level composite responders of the left buttock (defined as subjects 
with an improvement in severity from baseline of at least 2 levels of severity in the 
CR-PCSS of the left buttock assessed live by the Investigator and an improvement of 
severity from baseline of at least 2 levels of severity in the PR-PCSS of that same left 
buttock) (Days 22, 43, and 71) 
 Proportion of 2-level composite responders of the right buttock (defined as subjects 
with an improvement in severity from baseline of at least 2 levels of severity in the 
CR-PCSS of the right buttock assessed live by the Investigator and an improvement 
of severity from baseline of at least 2 levels of severity in the PR-PCSS of that same 
right buttock) (Days 22, 43, and 71) 
 Proportion of 2-level composite responders of at least one of two buttocks (Days 22, 
43, and 71). A subject will be considered a responder if this criterion is met in the left 
buttock or right buttock or both buttocks in that subject.  
 Proportion of 2-level composite responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both left and right buttocks. 
 Proportion of subjects at each level of the S-GAIS of the left buttock (Days 22, 43, 
and 71) 
 Proportion of subjects at each level of the S-GAIS of the right buttock (Days 22, 43, 
and 71) 
 Proportion of 1-level S-GAIS responders defined as subjects with a response of at 
least 1 (improved) in the S- GAIS of the left buttock (Days 22, 43, and 71) 

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 Proportion of 1-level S-GAIS responders defined as subjects with a response of at 
least 1 (improved) in the S- GAIS of the right buttock (Days 22, 43, and 71) 
 Proportion 1-level S-GAIS responders of at least one buttock (Days 22, 43, and 71). 
A subject will be considered a responder if this criterion is met in the left buttock or 
right buttock or both buttocks in that subject. 
 Proportion of 1-level S-GAIS responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both left and right buttocks. 
 Proportion of subjects at each level of the I-GAIS of the left buttock (Days 22, 43, 
and 71) 
 Proportion of subjects at each level of the I-GAIS of the right buttock (Days 22, 43, 
and 71) 
 Proportion of 1-level I-GAIS responders (defined as subjects with a response of at 
least 1 (improved) in the Investigator GAIS assessment) of at least one buttock 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in the left buttock or right buttock or both buttocks in that subject.  
 Proportion of 1-level I-GAIS responders of two buttocks in the same individual 
(Days 22, 43, and 71). A subject will be considered a responder if this criterion is met 
in both left and right buttocks. 
 Proportion of subjects at each level of the subject satisfaction with cellulite treatment 
(Day 71) 
 Proportion of satisfied responders (defined as subjects with a response of at least 1 
(ie, 1-Satisfied or 2-Very Satisfied) in the subject satisfaction with cellulite treatment 
assessment (Day 71) 
17.6. 
Safety Analyses 
Safety variables include adverse events, laboratory parameters, vital signs, ECG parameters, and 
physical examinations. For each safety parameter, the last assessment made prior to the first dose 
of study drug will be used as the baseline for all analyses of that safety parameter. 
17.6.1. 
Prior, Concomitant, and Follow-up Medication 
The World Health Organization (WHO) Drug Dictionary will be used to classify prior and 
concomitant medications by therapeutic class. Prior medication will be defined as any 
medication taken prior to the first dose of study drug. Concomitant medication is defined as any 
medication taken on or after the date of first dose of study drug. 
Prior and concomitant medication use will be summarized descriptively by the number and 
percentage of subjects for each preferred term (generic name from WHO dictionary) by 
treatment. Multiple use of the same medication by a subject will be counted only once. 

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17.6.2. 
Study Drug Exposure 
The following information regarding treatment will be summarized per each treated buttock by 
treatment group: 
 Total number of treatment visits 
 Number of subjects who had treatment session done or treatment session not done at 
each treatment visit 
 For subjects who had the treatment session done, the number of subjects who got all 
24 injections at the treatment visit or who received less than 24 injections 
 Number of injections given at each treatment visit  
 Number of dimples treated at each treatment visit  
 Average number of injections per dimple at each treatment visit  
Subjects who did not receive all 3 treatment visits and who did not receive 24 injections at a 
treatment visit will be listed. 
17.6.3. 
Measurement of Treatment Compliance 
Not applicable (the study drug is administered at the site by the study investigator). 
17.6.4. 
Adverse Events 
The Medical Dictionary for Regulatory Activities (MedDRA) will be used to code AEs. 
An AE (classified by preferred term) that started on or after the date of the first dose of the study 
drug will be considered a TEAE if it was not present prior to the first dose of study drug, or was 
present prior to the first dose of study drug but increased in intensity during the treatment period. 
If more than 1 AE is reported prior to the first dose of study drug and coded to the same 
preferred term, then the AE with the greatest intensity will be used as the benchmark for 
comparison to the AEs occurring during the treatment period which were also coded to that 
preferred term. Any AE present prior to the first dose of study drug that increases in intensity 
during the treatment period will be re-entered with a new start date of the date of increased 
intensity. 
Descriptive statistics (the number and percentage) for subjects reporting TEAEs in each 
treatment group will be tabulated by system organ class and preferred term; by system organ 
class, preferred term, and severity; and by system organ class, preferred term, and relationship to 
study drug. If more than 1 AE is coded to the same preferred term for the same subject, the 
subject will be counted only once for that preferred term using the most severe and most related 
occurrence for the summarization by severity and by relationship to the study drug. 
The by-frequency summaries will also include incidence of the SAEs and non-SAEs by preferred 
term that at least 2% of the subjects in one treatment group. Duration of AEs will be tabulated by 
treatment group. 
Fisher exact test will be used to compare EN3835 to placebo. 

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Listings will be presented for subjects with SAEs, subjects with AEs leading to discontinuation 
of study or study drug, and subjects who die (if any). 
17.6.5. 
Vital Signs 
Descriptive statistics for vital signs (eg, systolic and diastolic blood pressure, pulse rate, and 
body weight) and their changes from baseline at each visit and at the end of study will be 
presented by treatment group. 
Vital sign values are potentially clinically important (PCI) if they meet both the observed value 
criteria and the change from baseline criteria. The criteria for PCI vital sign values will be 
detailed in the Statistical Analysis Plan (SAP). The PCI percentages will be calculated relative to 
the number of subjects with baseline and at least one post-baseline assessment. A supportive 
listing of subject values will be provided including the subject ID, study center, treatment group, 
baseline and post-baseline values. 
The change from baseline for vital signs parameters are compared between EN3835 and placebo 
using an analysis of variance (ANOVA) with a factor of drug (EN3835 or placebo) while Fisher 
exact test will be used for the incidence of PCI values. 
17.6.6. 
Clinical Laboratory Parameters 
Descriptive statistics for clinical laboratory values in International System of Units (SI units) and 
changes from baseline at Day 71 will be presented by treatment group for each clinical 
laboratory parameter. 
The number and percentage of subjects with potentially clinically important (PCI) post-baseline 
clinical laboratory values will be tabulated by treatment group. The criteria for PCI laboratory 
values will be detailed in the Statistical Analysis Plan (SAP). The PCI percentages will be 
calculated relative to the number of subjects with at least one post-baseline assessment. A 
supportive listing of subjects with post-baseline PCI values will be provided, including the 
subject ID, study center, treatment group, baseline and post-baseline values. 
The change from baseline for clinical laboratory parameters are compared between EN3835 and 
placebo using an ANOVA with a factor of drug (EN3835 or placebo) while Fisher exact test will 
be used for the incidence of PCI values. 
17.6.7. 
Electrocardiogram 
Not applicable (ECG is done only at screening for the subject’s enrollment eligibility). 
17.6.8. 
Physical Examination 
Body weight and BMI at Day 22, Day 43, and Day 71 as well as their change from baseline 
(Day 1) at those time points will be presented by treatment group. 
17.6.9. 
Other Safety Measurements 
Not applicable. 

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17.7. 
Pharmacokinetic Analyses 
Not applicable. 
17.8. 
Pharmacodynamic Analyses 
Not applicable. 
17.9. 
Other Data (eg, Health Economics/QOL, Pharmacogenetic, etc) 
Not applicable. 
17.10. 
Interim Analysis 
No interim analysis is planned for this study. 
17.11. 
Statistical Software 
Statistical analyses will be performed using Version 9.3 (or higher) of SAS® (SAS Institute, 
Cary, NC). 
 

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18.5. 
Study Drug Accountability 
A drug inventory form must be kept current by the site staff designated to be responsible for 
reconstitution and must be made available to the clinical monitor, Endo employees, IRB/IEC, 
and regulatory agencies for routine inspection and accountability during monitoring visits. When 
instructed by Endo, the Investigator agrees to return all original used or unused study drug kits to 
Endo's return vendor. 
18.5.1. 
Study Drug Handling and Disposal 
The Investigator agrees not to supply study drug to any person except to those subjects enrolled 
in the study. The Investigator is responsible for recording the receipt and use of all drugs 
supplied and for ensuring the supervision of the storage and allocation of these supplies. All used 
and unused study drug will be returned, and unit counts will be performed whenever medication 
is returned. The site must account for all study drug received and its use. At the end of the study, 
all used and unused drug supplies will be returned to Endo’s return vendor. 
 

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19. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
19.1. 
Source Documents 
Source documents include but are not limited to original documents, data and records such as 
hospital/medical records (including electronic health records), clinic charts, lab results, subject 
diaries, data recorded in automated instruments, microfilm or magnetic media, and pharmacy 
records, etc. This study allows for direct data entry (DDE) for selected data points as outlined 
below: 
 PR-PCSS 
 CR-PCSS 
 Hexsel CSS 
 S-GAIS 
 I-GAIS 
 Subject Satisfaction with Cellulite Treatment Assessment 
All other data points, at a minimum, should have supporting source documentation for entries in 
the eCRF. 
19.2. 
Study Monitoring 
A representative of Endo Pharmaceuticals Inc. will meet with the Investigator and his/her staff 
prior to the entrance of the first subject to review study procedures and methods of recording 
findings in the eCRF. 
After enrollment of the first subject, an Endo Pharmaceuticals Inc. representative will be 
assigned to periodically monitor each Investigator site for study progress and to verify that 
standards of Good Clinical Practice (GCP) were followed. The Investigator is expected to 
prepare for the monitor visit, ensuring that all source documents, completed eCRFs, signed 
consent forms and other study related documents are readily available for review. 
19.3. 
Audits and Inspections 
The Investigator shall permit audits and inspections by the Sponsor, its representatives and 
members of regulatory agencies. The Investigator should immediately notify the Sponsor of an 
upcoming FDA or other regulatory agency inspection. 
19.4. 
Institutional Review Board (IRB) 
The Investigator shall permit members of the IRB/IEC to have direct access to source 
documents. 

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19.5. 
Data Recording and Documentation 
All data recordings and source documentation (including electronic health records) must be made 
available to the Sponsor (or designee), FDA and any other regulatory agencies that request 
access to study records, including source documents, for inspection and copying, in keeping with 
federal and local regulations. 
 

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20. 
QUALITY CONTROL AND QUALITY ASSURANCE 
Steps to assure the accuracy and reliability of data include the selection of qualified principal 
investigators and appropriate study centers, review of protocol procedures with the principal 
investigators and associated personnel prior to start of the study, and periodic monitoring visits 
conducted by the Sponsor or Sponsor representative. Significant and/or repeated non-compliance 
will be investigated and remedial action instituted when appropriate. Failure to comply with 
remedial actions may result in investigator site termination and regulatory authority notification. 
The Sponsor or its designee will utilize qualified monitors to review and evaluate activities 
conducted at Investigator Sites. 
The data will be entered into the clinical study database and verified for accuracy, following 
procedures defined by the Sponsor (or designee). Data will be processed and analyzed following 
procedures defined by the Sponsor (or designee). 
The study will be monitored and/or audited at intervals to ensure that the clinical study is 
conducted and data are generated, documented (recorded), and reported in compliance with the 
Study Protocol; International Conference on Harmonisation (ICH), E6 consolidated guidelines; 
and other applicable regulations. The extent, nature, and frequency of monitoring and/or audits 
will be based on such considerations as the study objectives and/or endpoints, the purpose of the 
study, study design complexity, and enrollment rate. At the conclusion of a program, a 
compliance statement will be generated by the Sponsor (or designee) listing all audit activities 
performed during the clinical study. 
 

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21. 
ETHICS 
21.1. 
Ethics Review 
Approval by the IRB/IEC prior to the start of the study will be the responsibility of the 
Investigator. A copy of approval documentation will be supplied to Endo Pharmaceuticals Inc. 
along with a roster of IRB members that demonstrates appropriate composition (a Department of 
Health and Human Services [DHHS] Assurance Number will satisfy this requirement). 
The study protocol, the informed consent form, advertisements, materials being provided to 
subjects and amendments (if any) will be approved to IRB/IECs at each study center in 
conformance with ICH E6, the Code of Federal Regulations (CFR), Title 21, Part 56 and any 
other applicable local laws. The Investigator is responsible for supplying the IRB/IEC with a 
copy of the current IB, Package Insert, or SPC as well as any updates issued during the study. 
During the course of the study, the Investigator will provide timely and accurate reports to the 
IRB/IEC on the progress of the study, at intervals not exceeding 1 year (or as appropriate), and 
will notify the IRB/IEC of SAEs or other significant safety findings, per the policy of the 
IRB/IEC. At the conclusion of the study, the Investigator will submit a final report or close out 
report to the IRB/IEC and provide a copy to Endo Pharmaceuticals Inc. 
Any amendment to this protocol will be provided to the Investigator in writing by Endo 
Pharmaceuticals Inc. No protocol amendment may be implemented (with the exceptions noted 
below) before it has been approved by the IRB and the signature page, signed by the 
Investigator, has been received by Endo Pharmaceuticals Inc. Where the protocol is amended to 
eliminate or reduce the risk to the subject, the amendment may be implemented before IRB 
review and approval. However, the IRB must be informed in writing of such an amendment and 
approval obtained within reasonable time limits. Deviating from the protocol is permitted only if 
absolutely necessary for the safety or clinical management of the subject, and must be 
immediately reported to Endo Pharmaceuticals Inc. 
The Investigator will be responsible for supplying updated safety and/or study information to 
study subjects as it becomes available. 
21.2. 
Ethical Conduct of the Study 
This clinical study is designed to comply with the ICH Guidance on General Considerations for 
Clinical Trials (62 FR 6611, December 17, 1997), Nonclinical Safety Studies for the Conduct of 
Human Clinical Trials for Pharmaceuticals (62 FR 62922, November 25, 1997), Good Clinical 
Practice: Consolidated Guidance (62 FR 25692, May 9, 1997) and 21 CFR parts 50, 54, 56  
and 312. 
The study will be conducted in full compliance with ICH E6, the FDA guidelines for GCP and in 
accordance with the ethical principles that have their origins in the Declaration of Helsinki 
defined in 21 CFR, 312.120. 

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21.3. 
Subject Information and Consent 
Subjects, after having the study explained to them and an opportunity to have their questions 
answered sufficiently, will give voluntary and written informed consent (in compliance with ICH 
E6, 4.8 and 21 CFR Parts 50 and 312) before participating in any study-related procedures. The 
consent shall be written in a language understandable to the subject. Subjects unable to read 
(illiterate) shall have the consent process performed in the presence of an independent witness 
who shall also sign the consent. Each subject will read, assent understanding, and sign an 
instrument of informed consent after having had an opportunity to discuss the study and consent 
documents with the Investigator before signing, and will be made aware that she may withdraw 
from the study at any time. 
In addition to obtaining informed consent/assent, the Investigator is responsible for obtaining any 
additional documentation to demonstrate compliance with local privacy laws applicable to 
activities performed. 
The consent/assent process shall be recorded in source documents. Signed copies of the informed 
consent and/or assent will be given to the Subject/LAR and originals will be placed in the 
Investigator study files. 
A unique Subject identification number will be assigned according to section 12.1.2.2 at the time 
that the Subject signs the informed consent form. 
 

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22. 
DATA HANDLING AND RECORDKEEPING 
22.1. 
Data Collection 
Endo will provide an electronic data capture (EDC) system for this study. Data collection will 
involve the use of an EDC system to which only authorized personnel will have access. The 
system will be secured to prevent unauthorized access to the data or the system. This will include 
the requirement for a user ID and password to enter or change data. The level of access to the 
EDC system will be dependent on the person’s role in the study. 
Study data will be collected from source documents and entered into an eCRF within the EDC 
system. The Investigator will be responsible for ensuring the eCRFs are completed in a timely 
manner relative to the subject’s visit. In addition to periodic monitoring occurring within the 
system by a Sponsor monitor, programmatic edit checks will be used to review EDC data for 
completeness, logic, and adherence to the study protocol. As a result of this monitoring and these 
checks, queries may be issued electronically to the clinical study sites and closed electronically 
by the monitor, data management staff or authorized staff at the study site. Additionally, the 
Investigator will review eCRFs, ensure all missing or corrected data is provided and will sign the 
eCRF pages with an electronic signature. 
An electronic audit trail will be maintained in the EDC system to track all changes made to data 
entered in the eCRF. Data will be retrievable in such a fashion that all information regarding 
each individual subject is attributable to that subject. Unless otherwise indicated, all data 
captured in the eCRF must first be captured in source documents. Data that can be directly 
recorded in the eCRF will be clearly identified in the section(s) of the protocol that describes the 
assessment(s). 
Data entries will be corrected by changing the entry in the EDC system. Any changes or 
corrections to eCRF data will be electronically tracked and will include the reason for correction, 
who made the correction, and the date/time stamp when the correction was made within the audit 
trail of the EDC system. 
In addition, any contact with the subject via telephone or other means that provide significant 
clinical information must be documented in source documents as described above. 
22.2. 
Study Documentation 
Upon study completion, the Investigator will be provided with complete electronic copies of the 
case report form (CRF) data for his/her files. 

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23. 
REPORTING AND PUBLICATION 
All data generated in this study are the property of Endo Pharmaceuticals Inc. An integrated 
clinical and statistical report will be prepared at the completion of the study. 
Publication of the results by the Investigator will be subject to mutual agreement between the 
Investigator and Endo Pharmaceuticals Inc. 
 

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24. 
INVESTIGATOR OBLIGATIONS 
24.1. 
Regulatory Documents 
The Investigator is responsible for creating and/or maintaining all study documentation required 
by 21CFR 50, 54, 56 and 312, ICH, E6 section 8, as well as any other documentation defined in 
the protocol or the Investigator Agreement. The Investigator must maintain the documentation 
relating to this study and permit Endo Pharmaceuticals Inc. or a member of a regulatory agency 
access to such records. 
The Investigator must provide the following key documents to Endo Pharmaceuticals Inc. prior 
to the start of the study: 
 A completed and signed Form FDA 1572. If during the course of the study any 
information reported on the Form FDA 1572 changes, a revised Form FDA 1572 
must be completed and returned to Endo Pharmaceuticals Inc. for submission to the 
FDA. For studies executed outside the United States, documentation required by the 
governing regulatory authority may be substituted for the Form FDA 1572. 
 A fully executed contract 
 The Investigator’s Statement page in this protocol signed and dated by the 
Investigator and any subsequent amendment signature pages 
 The IB acknowledgment of receipt page 
 Curricula vitae for the Principal Investigator and all sub-Investigators listed on Form 
FDA 1572, including a copy of each physician’s license (if applicable) 
 A copy of the original IRB/IEC approval for conducting the study. If the study is 
ongoing, renewals must be submitted at yearly intervals or shorter intervals defined 
by the IRB/IEC. All subsequent modifications must be submitted and approved by the 
IRB, as described in section 21.1 
 A copy of the IRB/IEC-approved informed consent form 
 A list of IRB/IEC members or DHHS Assurance Number 
 Laboratory certifications and normal ranges (if local labs are required by the protocol) 
 A financial disclosure agreement completed and signed by the Investigator and all 
sub-Investigators listed on Form FDA 1572. Investigator site staff that submitted an 
initial financial disclosure are also responsible for informing Endo Pharmaceuticals 
Inc. of any changes to their initial financial disclosure form 1 year after the 
completion of the study 
A complete list of required regulatory documents will be supplied by Endo Pharmaceuticals Inc. 
or its representative. 

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24.2. 
Delegation of Responsibilities and Adequate Resources 
The Investigator should have adequate time to conduct the study properly and should have an 
adequate number of qualified staff to assist with the conduct of the study. The Investigator shall 
delegate tasks only to individuals qualified by education, training and experience to perform the 
delegated tasks. The Investigator shall have direct oversight of all delegated activities and shall 
document delegation of responsibilities. The Investigator is responsible for ensuring all delegated 
staff have been properly trained on the protocol and their assigned study responsibilities. 
24.3. 
Medical Care of Study Subjects 
The Investigator and/or a qualified sub-Investigator shall be responsible for the subjects’ medical 
care. Any unrelated medical condition discovered during the course of the study should be 
communicated to the subject so that they may seek appropriate medical care. The Investigator 
will report all AEs as required by the protocol (section 14.5). The Investigator will inform study 
subjects of new information regarding the study drug as it becomes available. 
24.4. 
Use of Investigational Materials 
The Investigator will acknowledge that the study drug supplies are investigational and as such 
must be used strictly in accordance with the protocol and only under the supervision of the 
Principal Investigator or sub-Investigators listed on Form FDA 1572 (or other regulatory 
document, depending on region). Study drug must be stored in a safe and secure location. At 
study initiation, a representative from Endo Pharmaceuticals Inc. will inventory the study drug at 
the site. The Investigator must maintain adequate records documenting the receipt and 
disposition of all study supplies. Endo Pharmaceuticals Inc. or its representative will supply 
forms to document total inventory as well as subject specific accountability. The Investigator is 
responsible for monitoring subject’s use of the study drug to ensure compliance with the 
protocol. All study supplies shall be returned to Endo Pharmaceuticals Inc. or its designee. 
24.5. 
Retention of Records 
Federal and local regulations require that the Investigator retain a copy of all regulatory 
documents and records that support the data for this study (eg, informed consents, laboratory 
reports, source documents, study drug dispensing records) for whichever of the following is the 
longest period of time: 
 A period of 2 years following the final date of approval by the FDA or other 
regulatory agency of the study drug for the purposes that were the subject of the 
investigation; or 
 A period of 5 years following the date on which the results of the investigation were 
submitted to the FDA or other regulatory agency in support of, or as part of, an 
application for a research or marketing permit for the study drug for the purposes that 
were the subject of the investigation 
Endo Pharmaceuticals Inc. will notify Investigators once one of the above 2 timeframes has been 
satisfied. 

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If the investigation does not result in the submission of the data in support of, or as part of, an 
application for a research or marketing permit, records must be retained for a period of 2 years 
following notification by Endo Pharmaceuticals Inc. that the entire clinical investigation (not 
merely the Investigator’s portion) is completed, terminated, or discontinued or 2 years following 
withdrawal of the Investigational New Drug application (IND)/Clinical Trial Authorization 
(CTA) or request for marketing approval (New Drew Application [NDA]/Marketing 
Authorization Application [MAA]). 
If the Investigator retires, relocates, or for other reasons withdraws from the responsibility of 
keeping the study records, custody must be transferred to a person who will accept the 
responsibility. Endo Pharmaceuticals Inc. must be notified in writing of the name and address of 
the new custodian. Study records should not be destroyed without consultation with Endo 
Pharmaceuticals Inc. 
24.6. 
Subject Confidentiality 
All subject records submitted to Endo Pharmaceuticals Inc. or its designee will be identified only 
by initials and subject number. Subjects’ names are not to be transmitted to Endo 
Pharmaceuticals Inc. The Investigator will keep a Master Subject List on which the identification 
number and the full name, address, and telephone number of each subject are listed. It is the 
Investigators’ responsibility to inform study subjects that representatives of the Sponsor, FDA, or 
other regulatory agencies may review all records that support their participation in the study. The 
Investigator will adhere to all privacy laws to which he/she is subject. 
 

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25. 
TERMINATION OF STUDY 
The Sponsor has the right to suspend or terminate the study at any time. The study may be 
suspended or terminated for any reason. 
 

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26. 
INVESTIGATOR’S STATEMENT 
I agree to conduct the study in accordance with the protocol, and with all applicable government 
regulations and Good Clinical Practice guidance. 
 
 
 
_____/_____/______ 
Investigator’s Signature 
Date 
 
 
 
Typed Name of Investigator 
 

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27. 
REFERENCES 
1. Khan MH, Victor F, Rao B, Sadick NS. Treatment of cellulite: Part I. Pathophysiology. 
J Am Acad Dermatol 2010;62(3):361-70. 
2. Hexsel D, de Oliveira Dal’Forno T, Mazzuco R. Definition, clinical aspects, 
classifications, and diagnostic techniques. In: Goldman MP, Hexsel D, eds. Cellulite: 
Pathophysiology and Treatment. 2nd ed. New York, NY: Informa Healthcare; 
2010:13-21. 
3. Rawlings AV. Cellulite and its treatment. Int J Cosmetic Sci. 2006;28(3):175-90. 
4. Terranova F, Berardesca E, Maibach H. Cellulite: nature and aetiopathogenesis. Int J 
Cosmetic Sci. 2006;28(3):157-67. 
5. Avram MM. Cellulite: a review of its physiology and treatment. J Cosmet Laser Ther. 
2004;6(4):181-5. 
6. Khan MH, Victor F, Rao B, Sadick NS. Treatment of cellulite: Part II. Advances and 
controversies. J Am Acad Dermatol 2010;62(3):373-84. 
7. Collis N, Elliot LA, Sharpe C, Sharpe DT. Cellulite treatment: a myth or reality: a 
prospective randomized, controlled trial of two therapies, endermologie and 
aminophylline cream. Plast Reconstr Surg. 1999;104(4):1110-4. 
8. Hexsel DM, Mazzuco R. Subcision: a treatment for cellulite. Int J Dermatol. 
2000;39(7):539-44. 
9. Boyce S, Pabby A, Chuchaltkaren P, Brazzini B, Goldman MP. Clinical evaluation of a 
device for the treatment of cellulite: Triactive. Am J Cosmet Surg. 2005;22:233-7. 
10. DiBernardo BE. Treatment of cellulite using a 1440-nm pulsed laser with one-year 
follow-up. Aesthet Surg J. 2011;31(3):328-41. 
11. Investigational Brochure: Collagenase Clostridium Histolyticum for Injection 
(AA4500/EN3835), Version 7.0. Endo Pharmaceuticals Inc.; May 2016. 
12. Hexsel DM, Dal’Forno T, Hexsel CL. A validated photonumeric cellulite severity scale. 
J Eur Acad Dermatol Venereol. 2009;23(5):523-8. 
13. Nürnberger F, Müller G. So-called cellulite: an invented disease. J Dermatol Surg Oncol. 
1978;4(3):221-9. 
 

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APPENDIX A. DOCUMENTS REQUIRED PRIOR TO INITIATION OF 
THE STUDY 
As a sponsor of a clinical study, Endo Pharmaceuticals Inc. has an obligation to ensure that the 
study will be conducted by a qualified Investigator with sufficient resources of time, personnel, 
and physical facilities to conduct the study and to ensure that the Investigator understands and 
agrees to comply with the protocol, applicable regulations, policies, and procedures. The 
following documentation is required: 
From the Principal Investigator 
1. A signed agreement to perform the study per protocol (the signature page will suffice). 
2. A signed Letter of Financial Agreement (including confidentiality statement). 
3. Name(s) of the Principal Investigator and of all sub-Investigator(s) 
4. All address(es) of the clinical site(s). 
5. A current medical license valid where he/she practices and a current curriculum vitae for 
the Principal Investigator (signed and dated) and all sub-Investigators, to contain at least 
the following elements: 
a. For physicians: 
i. Date of degree in Medicine 
ii. Name of the Institution granting the degree in Medicine 
iii. Previous clinical postings with dates 
b. For non-physician allowed by national law or regulations to act as clinical 
Investigators: 
i. Date and description of most advanced degree 
ii. Name of the Institution granting the degree in number (i) 
iii. Other accreditation or qualifications relevant to the study 
iv. Previous postings with dates 
v. Name and qualification (see 5a above) of the physician or dentist in charge of 
study subjects 
Note: If a non-physician is serving as Principal Investigator, then a qualified physician 
must be assigned as a sub-Investigator for the trial, to be responsible for all trial-related 
medical decisions. 
6. Written notification of Institutional Review Board/Independent Ethics Committee/Human 
Research Ethics Committee (IRB/IEC/HREC) approval. The minimum requirements are 
as follows: 
a. Dated letter, including: 
i. The date on which the meeting for the review of the study protocol took place 
ii. Study protocol/amendment number, and version date 

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iii. A clear statement of approval of the protocol and the informed consent text with 
version date, and authorization for the study to proceed 
iv. If the Investigator or any sub-Investigator is a part of the IRB/IEC/HREC 
Review Board, assurance that the Investigator abstained from voting at the 
meeting(s) when the study was discussed. 
b. A dated list of the members and their occupations 
c. A specimen copy of the Committee-approved informed consent text to be used in the 
study 
7. Food and Drug Administration (FDA) Form 1572 (for studies submitted under a US 
Investigational New Drug application [IND]). 
8. Financial Disclosure Certification or Certification of Non-Disclosure (for studies to be 
submitted for a US New Drug Application/Biologics License Application [NDA/BLA]). 
Other 
Any other documentation required by national law or regulations to be in the possession of the 
sponsor or the Investigator for study participation or study initiation. 

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APPENDIX B. PATIENT-REPORTED PHOTONUMERIC CELLULITE SEVERITY SCALE (PR-PCSS) 
FOR THE BUTTOCK 
 
 

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APPENDIX C. CLINICIAN-REPORTED PHOTONUMERIC CELLULITE SEVERITY SCALE 
(CR-PCSS) FOR THE BUTTOCK 
 

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APPENDIX D. HEXSEL DM, DAL’FORNO T, HEXSEL CL. A 
VALIDATED PHOTONUMERIC CELLULITE SEVERITY 
SCALE. J EUR ACAD DERMATOL VENEREOL. 
2009;23(5):523-8 

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Statistical Analysis Plan (SAP) Module 1 – Study EN3835-303 
30-Aug-2018 
Endo Pharmaceuticals Inc. 
Page 1 
 
 
 
 
 
 
SAP MODULE 1 – DETAILED STATISTICAL METHODOLOGY 
STUDY EN3835-303 
A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-
CONTROLLED STUDY OF EN3835 IN THE TREATMENT OF 
EDEMATOUS FIBROSCLEROTIC PANNICULOPATHY 
 
Version 3.0 
August 30, 2018 
 
Endo Pharmaceuticals Inc. 
1400 Atwater Drive 
Malvern, PA 19355 
USA 
 

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TABLE OF CONTENTS 
1. 
STUDY OBJECTIVE .................................................................................................10 
2. 
STUDY DESIGN AND MEASURES .......................................................................10 
2.1. 
Inclusion Criteria ........................................................................................................13 
2.2. 
Exclusion Criteria .......................................................................................................13 
2.3. 
Selection of Target Buttock ........................................................................................15 
2.4. 
Selection of Dimples and Injection Sites During Treatment Visits ............................15 
2.4.1. 
Selecting and Marking the Dimples ...........................................................................15 
2.4.2. 
Selecting Injection Sites .............................................................................................16 
2.5. 
Randomization and Study Drug Administration ........................................................16 
2.5.1. 
Randomization ............................................................................................................16 
2.5.2. 
Blinding and Unblinding ............................................................................................16 
2.5.3. 
Study Drug Administration.........................................................................................16 
2.6. 
Digital Photographs ....................................................................................................17 
2.7. 
Patient Reported Photonumeric Cellulite Severity Scale (PR-PCSS) ........................17 
2.8. 
Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) ....................18 
2.9. 
Patient Reported Cellulite Impact Scale (PR-CIS) .....................................................18 
2.10. 
Subject Self-rating Scale (SSRS) ................................................................................19 
2.11. 
Global Assessment Ratings ........................................................................................20 
2.11.1. 
Subject Global Aesthetic Improvement Scale (S-GAIS)............................................20 
2.11.2. 
Investigator Global Aesthetic Improvement Scale (I-GAIS) .....................................20 
2.11.3. 
Subject Satisfaction with Cellulite Treatment Assessment ........................................21 
2.12. 
Skin Assessment (Fitzpatrick Scale) ..........................................................................21 
2.13. 
Weight, Height, and BMI ...........................................................................................22 
2.14. 
Adverse Events ...........................................................................................................22 
2.15. 
Medical History ..........................................................................................................23 
2.16. 
Edematous Fibrosclerotic Panniculopathy Disease History .......................................23 
2.17. 
Physical Examination .................................................................................................23 
2.18. 
Vital Signs ..................................................................................................................23 
2.19. 
12-Lead Electrocardiogram ........................................................................................23 
2.20. 
Clinical Laboratory .....................................................................................................24 
2.21. 
Pregnancy Test ............................................................................................................24 

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2.22. 
Immunogenicity Samples ...........................................................................................24 
2.23. 
Concomitant Medications ...........................................................................................25 
2.24. 
Concomitant Procedures/Therapies ............................................................................25 
3. 
STUDY PARAMETERS............................................................................................25 
3.1. 
Subject Disposition .....................................................................................................25 
3.2. 
Number of Treatment Sessions ...................................................................................26 
3.3. 
Early Termination Visit Assessments .........................................................................26 
3.4. 
Treatment Groups .......................................................................................................26 
3.5. 
Efficacy Parameters ....................................................................................................27 
3.5.1. 
PR-PCSS .....................................................................................................................27 
3.5.1.1. 
Baseline PR-PCSS Rating ..........................................................................................27 
3.5.1.2. 
Change from Baseline PR-PCSS Rating ....................................................................27 
3.5.1.3. 
Subject PR-PCSS Responders for Target Buttock .....................................................27 
3.5.1.4. 
Subject PR-PCSS Responders for Non-target Buttock ..............................................27 
3.5.1.5. 
PR-PCSS Responders for at Least One Buttock .........................................................27 
3.5.1.6. 
PR-PCSS Responders for Two Buttocks ....................................................................27 
3.5.2. 
S-GAIS .......................................................................................................................28 
3.5.2.1. 
S-GAIS Rating ............................................................................................................28 
3.5.2.2. 
S-GAIS Responders for Target Buttock .....................................................................28 
3.5.2.3. 
S-GAIS Responders for Non-target Buttock ..............................................................28 
3.5.2.4. 
S-GAIS Responders for at Least One Buttock ...........................................................28 
3.5.2.5. 
S-GAIS Responders for Two Buttocks.......................................................................28 
3.5.3. 
PR-CIS ........................................................................................................................28 
3.5.3.1. 
Baseline PR-CIS Item Scores .....................................................................................29 
3.5.3.2. 
Change from Baseline PR-CIS Item Scores ...............................................................29 
3.5.3.3. 
Responders Based on PR-CIS Item Scores ................................................................29 
3.5.3.4. 
Baseline PR-CIS Total Scores ....................................................................................29 
3.5.3.5. 
Change from Baseline PR-CIS Total Scores ..............................................................29 
3.5.3.6. 
Responders Based on PR-CIS Total Score .................................................................29 
3.5.3.7. 
Baseline PR-CIS Abbreviated Total Scores ...............................................................29 
3.5.3.8. 
Change from Baseline PR-CIS Abbreviated Total Scores .........................................29 
3.5.3.9. 
Responders Based on PR-CIS Abbreviated Total Scores ...........................................30 
3.5.4. 
SSRS ...........................................................................................................................30 

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3.5.4.1. 
SSRS Rating Scores ....................................................................................................30 
3.5.4.2. 
Subject 1-Level SSRS Responders .............................................................................30 
3.5.5. 
Subject Global Satisfaction With Cellulite Treatment ...............................................30 
3.5.5.1. 
Subject Global Satisfaction With Cellulite Treatment Rating ....................................30 
3.5.5.2. 
Subject-satisfied Responders ......................................................................................30 
3.5.6. 
CR-PCSS ....................................................................................................................30 
3.5.6.1. 
Investigator Baseline CR-PCSS Rating ......................................................................30 
3.5.6.2. 
Investigator Change from Baseline CR-PCSS Rating ................................................30 
3.5.6.3. 
CR-PCSS Responders for Target Buttock ..................................................................30 
3.5.6.4. 
CR-PCSS Responders for Non-target Buttock ...........................................................31 
3.5.6.5. 
CR-PCSS Responders for at Least One Buttock ........................................................31 
3.5.6.6. 
CR-PCSS Responders for Two Buttocks ...................................................................31 
3.5.7. 
I-GAIS ........................................................................................................................31 
3.5.7.1. 
I-GAIS Rating .............................................................................................................31 
3.5.7.2. 
I-GAIS Responders for Target Buttock ......................................................................31 
3.5.7.3. 
I-GAIS Responders for Non-target Buttock ...............................................................31 
3.5.7.4. 
I-GAIS Responders for at Least One Buttock ............................................................32 
3.5.7.5. 
I-GAIS Responders for Two Buttocks .......................................................................32 
3.5.8. 
Subject (PR-PCSS)/Investigator (CR-PCSS) Composite Responders .......................32 
3.5.8.1. 
Composite Responders for Target Buttock .................................................................32 
3.5.8.2. 
Composite Responders for Non-target Buttock ..........................................................32 
3.5.8.3. 
Composite Responders for at Least One Buttock .......................................................33 
3.5.8.4. 
Composite Responders for Two Buttocks ..................................................................33 
3.6. 
Safety Parameters .......................................................................................................33 
3.6.1. 
Adverse Events ...........................................................................................................33 
3.6.1.1. 
Adverse Event Treatment Session ..............................................................................33 
3.6.1.2. 
Adverse Event Duration .............................................................................................34 
3.6.2. 
Vital Signs and Clinical Laboratories .........................................................................34 
3.6.2.1. 
Baseline Values and Change from Baseline Values ...................................................34 
3.6.2.2. 
Sponsor-defined Potentially Clinically Important Laboratory Values .......................34 
3.6.2.3. 
Sponsor-defined Potentially Clinically Important Vital Sign Values .........................34 
3.7. 
Other Parameters ........................................................................................................35 
3.7.1. 
Immunogenicity ..........................................................................................................35 

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3.7.2. 
Medical History ..........................................................................................................35 
3.7.3. 
Prior/Concomitant Medications ..................................................................................36 
3.7.4. 
Prior EFP Treatment ...................................................................................................36 
4. 
ANALYSIS POPULATIONS ....................................................................................36 
4.1. 
Safety Population ........................................................................................................36 
4.2. 
Intent-to-Treat (ITT) Population .................................................................................37 
4.3. 
Modified Intent-to-Treat (mITT) Population ..............................................................37 
4.4. 
Per-Protocol (PP) Population ......................................................................................37 
5. 
STATISTICAL METHODS .......................................................................................37 
5.1. 
Overview .....................................................................................................................37 
5.2. 
Analysis Centers .........................................................................................................39 
5.3. 
Missing Data Handling ...............................................................................................40 
5.4. 
Subjects Given Incorrect Treatment ...........................................................................40 
5.5. 
Subject Disposition .....................................................................................................40 
5.6. 
Demographics and Baseline Characteristics ...............................................................41 
5.7. 
EFP Risk Factors and EFP History .............................................................................41 
5.8. 
Cellulite Baseline Severity .........................................................................................42 
5.8.1. 
Cellulite Severity at Screening ...................................................................................42 
5.8.2. 
Cellulite Baseline Severity .........................................................................................42 
5.8.3. 
Cellulite Severity at Screening Versus Day 1.............................................................42 
5.9. 
Efficacy Evaluation ....................................................................................................42 
5.9.1. 
Overview of Treatment ...............................................................................................42 
5.9.2. 
Multiple Comparisons for Efficacy Endpoints ...........................................................43 
5.9.3. 
Primary Endpoint ........................................................................................................44 
5.9.4. 
Key Secondary Endpoints – Family #1 ......................................................................44 
5.9.5. 
Key Secondary Endpoints – Family #2 ......................................................................45 
5.9.6. 
Key Secondary Endpoints – Family #3 ......................................................................45 
5.9.7. 
Sensitivity Analyses ....................................................................................................45 
5.9.7.1. 
Multiple Imputation (MI) for Missing Data ...............................................................46 
5.9.7.2. 
Tipping Point Analysis ...............................................................................................47 
5.9.7.3. 
Missing Data Handled by a Last Observation (Post-dose) Carried Forward 
(LOCF) .......................................................................................................................48 
5.9.7.4. 
Other Sensitivity Analyses .........................................................................................48 

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5.9.8. 
Supportive Efficacy Endpoints ...................................................................................49 
5.9.8.1. 
Endpoints Based on Subject PR-PCSS Rating ...........................................................49 
5.9.8.2. 
Endpoints Based on Subject S-GAIS Rating ..............................................................50 
5.9.8.3. 
Endpoints Based on Subject PR-CIS Ratings .............................................................50 
5.9.8.4. 
Endpoints Based on SSRS Ratings .............................................................................51 
5.9.8.5. 
Endpoints Based on Subject Satisfaction With Cellulite Treatment ..........................51 
5.9.8.6. 
Endpoints Based on Investigator CR-PCSS Rating....................................................51 
5.9.8.7. 
Endpoints Based on Investigator I-GAIS Rating........................................................52 
5.9.8.8. 
Endpoints Based on Subject PR-PCSS Rating and Investigator CR-PCSS 
Rating ..........................................................................................................................53 
5.9.8.9. 
Change from Baseline in PR-PCSS by S-GAIS Rating at Day 71 .............................53 
5.9.8.10. 
By-center Exploratory Analyses .................................................................................54 
5.10. 
Safety Evaluation ........................................................................................................55 
5.10.1. 
Adverse Events ...........................................................................................................55 
5.10.1.1. 
Adverse Event Conventions .......................................................................................57 
5.10.2. 
Weight and BMI .........................................................................................................58 
5.10.3. 
Vital Signs ..................................................................................................................58 
5.10.4. 
Clinical Laboratory .....................................................................................................58 
5.10.5. 
Immunogenicity ..........................................................................................................58 
5.10.6. 
Concomitant Medications ...........................................................................................59 
6. 
DERIVED VARIABLES ...........................................................................................59 
6.1. 
Subject Level Variables ..............................................................................................59 
6.2. 
Safety Variables ..........................................................................................................60 
6.2.1. 
Adverse Events ...........................................................................................................60 
6.2.2. 
Laboratory Variables ..................................................................................................60 
6.3. 
Imputation of Partial Dates .........................................................................................61 
6.4. 
Relative Study Day/Treatment Session Study Day ....................................................61 
6.5. 
Conventions and Algorithms ......................................................................................61 
6.5.1. 
Summary Tables/Subject Listings Conventions .........................................................61 
7. 
INTERIM ANALYSES ..............................................................................................62 
8. 
SAMPLE SIZE CALCULATION ..............................................................................62 
9. 
TABLES, LISTINGS, AND GRAPH SHELLS.........................................................63 
10. 
CHANGE FROM PROTOCOL .................................................................................63 

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11. 
REVISION HISTORY ...............................................................................................64 
12. 
REFERENCES ...........................................................................................................65 
 

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LIST OF TABLES 
Table 1: 
Study EN3835-303 Assessments ................................................................................11 
Table 2: 
Subject Self-rating Scale (SSRS) ................................................................................20 
Table 3: 
Subject Global Aesthetic Improvement Scale (S-GAIS)............................................20 
Table 4: 
Investigator Global Aesthetic Improvement Scale (I-GAIS) .....................................21 
Table 5: 
Subject Satisfaction with Cellulite Treatment Assessment - Buttocks .......................21 
Table 6: 
Fitzpatrick Scale .........................................................................................................21 
Table 7: 
Clinical Laboratory Parameters ..................................................................................24 
Table 8: 
Sponsor-defined Potentially Clinically Important Laboratory Criteria ......................34 
Table 9: 
Sponsor-defined Potentially Clinically Important Vital Sign Criteria .......................35 
Table 10: Multiplicity Tests for Efficacy Endpoints ..................................................................44 
Table 11: Initial Seeds for Multiple Imputations ........................................................................46 
Table 12: Subject Level Derived Dataset Variables ...................................................................59 
Table 13: Adverse Event Variables by Event .............................................................................60 
Table 14: Adverse Event Variables by Subject ..........................................................................60 
Table 15: Previous Results as Bases for Sample Size ................................................................63 
Table 16: Changes from Protocol ...............................................................................................63 
Table 17: Revision History .........................................................................................................64 
 

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LIST OF ABBREVIATIONS AND DEFINITIONS 
Abbreviation 
Definition 
AE 
Adverse event 
ANCOVA 
Analysis of covariance 
ANOVA 
Analysis of variance 
AUX-I 
Clostridial Class I Collagenase 
AUX-II 
Clostridial Class II Collagenase 
BMI 
Body mass index 
CMH 
Cochran Mantel Haenszel 
CR-PCSS 
Clinician Reported Photonumeric Cellulite Severity Scale 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
EFP 
Edematous fibrosclerotic panniculopathy 
EN3835 
Purified lyophilized clostridial collagenase 
GAIS 
Global Aesthetic Improvement Scale 
I-GAIS 
Investigator Global Aesthetic Improvement Scale 
ISE 
Integrated summary of efficacy 
ITT 
Intent to treat 
IWRS 
Interactive web response system 
LOCF 
Last observation carried forward 
LSMEAN 
Least square mean 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Multiple imputation 
mITT 
Modified intent to treat 
MNAR 
Missing not at random 
PCI 
Potentially clinically important 
PP 
Per protocol 
PR-CIS 
Patient Reported Cellulite Impact Scale 
PR-PCSS 
Patient Reported Photonumeric Cellulite Severity Scale 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
Standard deviation 
SE 
Standard error 
S-GAIS 
Subject Global Aesthetic Improvement Scale 
SSRS 
Subject Self-rating Scale 
TEAE 
Treatment-emergent adverse event 
TP 
Tipping point 
WHO 
World Health Organization 
 

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1. 
STUDY OBJECTIVE 
The primary objective of this study is to assess the efficacy and safety of EN3835 in the 
treatment of edematous fibrosclerotic panniculopathy (EFP) commonly known as cellulite in 
adult women. 
2. 
STUDY DESIGN AND MEASURES 
This study is a Phase 3 randomized, double-blind, placebo-controlled study of the efficacy and 
safety of EN3835 in the treatment of EFP in adult women. Subjects will be screened for study 
eligibility within 14 days prior to enrolling in this study. Subjects with 2 treatment areas 
(bilateral buttocks) (also referred to as quadrants) with moderate or severe levels of cellulite as 
independently assessed by the subject using the Patient Reported Photonumeric Cellulite 
Severity Scale (PR-PCSS) and by the investigator using the Clinician Reported Photonumeric 
Cellulite Severity Scale (CR-PCSS). 
Once the eligibility of the buttocks is confirmed again on Day 1, subjects will be randomly 
assigned to 1 of 2 treatment groups, EN3835 1.68 mg total dose (0.84 mg per buttock) or 
placebo, in a 1:1 ratio within an investigational site. A treatment course will consist of 
3 treatment sessions (ie, Days 1, 22, and 43). Each treatment session will consist of 12 injections 
(0.3 mL per injection of EN3835 0.07 mg/injection or placebo) in each of the buttocks for a total 
volume of 7.2 mL. Selection of dimples to be treated in each buttock will be at the discretion of 
the investigator. End of study will occur at study Day 71. Of the two assigned eligible buttocks, 
one buttock will be randomly selected as the target buttock on Day 1 for the primary efficacy 
endpoint. The other (remaining) buttock will be considered the non-target buttock. Subjects, 
investigators, site personnel, and Endo personnel will be blinded to the identification of the target 
and non-target buttocks. 
At each treatment session, each of the buttocks will be photographed before and after marking 
dimples and injection sites while the subject is in a consistent, standardized relaxed standing 
pose. The subject will assess the digital photographic image (pre-marking) of each of the 
buttocks using the PR-PCSS to determine the severity of EFP in each of the buttocks. The 
subject will also evaluate each of the buttocks using a Subject Global Aesthetic Improvement 
Scale (S-GAIS). Subsequently, the investigator will conduct live assessments of each of the 
buttocks using the CR-PCSS. At Day 1, the subject will complete a Patient Reported Cellulite 
Impact Scale (PR-CIS) assessment and a Subject Self-rating Scale (SSRS) assessment. The 
subject assessments will always be completed prior to and independently of the investigator 
assessments at each treatment visit. The investigator will assess each of the buttocks using an 
Investigator Global Aesthetic Improvement Scale (I-GAIS). All the assessments must be done 
before the dimple marking. 
At Day 71 (End of Study/Early Termination), photographs of each of the buttocks will be taken 
and evaluated by the subject using the PR-PCSS. The investigator will conduct live assessments 
of each of the buttocks using the CR-PCSS. Global assessment evaluations will be completed by 
both the subject and the investigator. 
Table 1 contains the schedule of assessments. 

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Table 1: 
Study EN3835-303 Assessments 
Procedures 
Day -14 to -1 
Screening 
Day 1 
Treatment  
Visit 1 
Day 22 (± 3 d) 
Treatment  
Visit 2 
Day 43 (± 3 d) 
Treatment  
Visit 3 
Day 71 (+ 5 d) / 
End of Study / 
Early Termination 
Unscheduled 
Clinic Visit a 
Informed consent 
X 
 
 
 
 
 
Inclusion/exclusion 
X 
 
 
 
 
 
Digital photography 
X 
X b 
X b 
X b 
X 
X 
Medical history/EFP history including previous 
treatments 
X 
 
 
 
 
 
Prior/concomitant medications/procedures 
X 
X 
X 
X 
X 
X 
Physical examination: 
X 
 
 
 
 
 
• Body weight 
X 
 
X c 
X c 
X 
X 
• Height  
X 
 
 
 
 
 
• Fitzpatrick skin type 
X 
 
 
 
 
 
Vital signs 
X 
X d 
X d 
X d 
X 
X 
12-lead ECG 
X 
 
 
 
 
 
Collection of samples: 
• Clinical laboratory 
X 
 
 
 
X 
X 
• Anti-AUX-I/anti-AUX-II antibody level 
 
X c 
X c 
X c 
X 
 
• Pregnancy testing 
X e 
X c,e 
X c,e 
X c,e 
X e 
X 
Subject cellulite assessments f: 
• Patient Reported Photonumeric Cellulite 
Severity Scale (PR-PCSS) 
X g,h 
X c,g,h 
X c,g,h 
X c,g,h 
X g,h 
 
• Patient Reported Cellulite Impact Scale 
(PR-CIS) 
 
X c,g 
 
 
Xg 
 
• Subject Global Aesthetic Improvement 
(S-GAIS) 
 
 
X c,g,h 
X c,g,h 
X g,h 
 
• Subject Satisfaction With Cellulite Treatment 
Assessment 
 
 
 
 
X g 
 
• Subject Self-rating Scale (SSRS) 
 
X c 
 
 
X 
 

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Table 1: 
Study EN3835-303 Assessments (Continued) 
Procedures 
Day -14 to -1 
Screening 
Day 1 
Treatment  
Visit 1 
Day 22 (± 3 d) 
Treatment  
Visit 2 
Day 43 (± 3 d) 
Treatment  
Visit 3 
Day 71 (+ 5 d) / 
End of Study / 
Early Termination 
Unscheduled 
Clinic Visit a 
Investigator cellulite assessments: 
• Selection of dimples to be treated within the 
two buttocks 
 
X c 
X c 
X c 
 
 
• Marking the dimples and injection sites to be 
treated within the buttocks 
 
X c 
X c 
X c 
 
 
• Clinician Reported Photonumeric Cellulite 
Severity Scale (CR-PCSS) 
X 
X c,h 
X c,h 
X c,h 
X h 
 
• Investigator Global Aesthetic Improvement 
(I-GAIS)  
 
 
X c,h 
X c,h 
X c,h 
 
Confirm eligibility 
 
X c 
 
 
 
 
Randomize to treatment 
 
X c,i 
 
 
 
 
Study drug administration 
 
X 
X 
X 
 
 
Injection site reactions/local tolerability in the 
buttocks 
 
X 
X 
X 
X 
X 
Adverse events 
Monitored Throughout Study 
a During unscheduled visits, the Investigator or designee may perform any study procedure that they deem clinically necessary (eg, vital signs, clinical lab 
assessments, and pregnancy test). 
b Before and after marking the dimples and injection sites. 
c Before injection. 
d Up to 4 hours before injection; approximately 15 and 30 minutes after injection. Vital signs must be stable before the subject is discharged. 
e Serum pregnancy test on Screening visit and Day 71/EOS visit; urine pregnancy test on Day 1, Day 22, and Day 43 visits. 
f Subject assessments should be completed independently and prior to Investigator assessments at each visit. 
g Assessment made via photographs (if treatment visit, use photographs taken before marking dimples and injection sites). 
h Assessment of each of the 2 buttocks independently. 
i Before randomization, each of the subject’s buttocks must have ratings of 3 or 4 (moderate or severe) in both the CR-PCSS and PR-PCSS. 
NOTE: Subject cellulite assessments must be completed before the Investigator cellulite assessments are conducted at each visit.  
d=Days; ECG=Electrocardiogram; EFP=Edematous fibrosclerotic panniculopathy; EOS=End of study 

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2.1. 
Inclusion Criteria 
In order to be eligible to participate in the study, subjects must meet the following criteria: 
1. Voluntarily sign and date an informed consent agreement 
2. Be a female ≥18 years of age 
3. At Screening visit, have 2 bilateral buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as reported by the Investigator (CR-PCSS) 
4. At Day 1 visit, have 2 bilateral buttocks with each buttock having: 
a. a score of 3 or 4 (moderate or severe) as reported by the subject (PR-PCSS), and 
b. a score of 3 or 4 (moderate or severe) as reported by the Investigator (CR-PCSS) 
5. Be willing to apply sunscreen to the buttocks before each exposure to the sun while 
participating in the study (ie, Screening through end of study) 
6. Be judged to be in good health, based upon the results of a medical history, physical 
examination, and laboratory profile at Screening  
7. Have a negative serum pregnancy test at Screening and a negative urine pregnancy test 
before injection of study drug and be using a stable and effective contraception method 
(eg, abstinence, intrauterine device [IUD], hormonal [estrogen/progestin] contraceptives, 
or double barrier method) for at least 1 menstrual cycle prior to study enrollment and for 
the duration of the study; or be menopausal defined as 12 months of amenorrhea in the 
absence of other biological or physiological causes, as determined by the Investigator; or 
post-menopausal for at least 1 year; or be surgically sterile 
8. Be willing and able to cooperate with the requirements of the study 
9. Be able to read, complete and understand the patient reported outcomes rating 
instruments in English 
2.2. 
Exclusion Criteria 
Subjects who meet any of the following criteria will not be eligible to participate in the study: 
1. Has any of the following systemic conditions: 
a. Coagulation disorder 
b. Evidence or history of malignancy (other than excised basal-cell carcinoma) unless 
there has been no recurrence in at least 5 years 
c. History of keloidal scarring or abnormal wound healing 
d. Concurrent diseases or conditions that might interfere with the conduct of the study, 
confound the interpretation of the study results, or endanger the subject’s well-being. 
Any questions about concurrent diseases should be discussed with the Medical 
Monitor. 
e. Evidence of clinically significant abnormalities on physical examination, vital signs, 
electrocardiogram (ECG), or clinical laboratory values. 

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2. Has any of the following local conditions in the areas to be treated: 
a. History of lower extremity thrombosis or post-thrombosis syndrome 
b. Vascular disorder (eg, varicose veins, telangiectasia) in area to be treated 
c. Inflammation or active infection  
d. Severe skin laxity, flaccidity, and/or sagging 
e. Active cutaneous alteration including rash, eczema, psoriasis, or skin cancer 
f. Has a tattoo and/or a mole located within 2 cm of the site of injection 
3. Requires the following concomitant medications before or during participation in the 
trial: 
a. Anticoagulant or antiplatelet medication or has received anticoagulant or antiplatelet 
medication (except for ≤150 mg aspirin daily) within 7 days before injection of study 
drug 
4. Has used any of the following for the treatment of EFP on a buttock within the timelines 
identified below or intends to use any of the following at any time during the course of 
the study: 
a. Liposuction in a buttock during the 12-month period before injection of study drug 
b. Injections (eg, mesotherapy); radiofrequency device treatments; laser treatment; 
buttock implant treatment; cryolipolysis; or surgery (including subcision and/or 
powered subcision) within a buttock during the 12-month period before injection of 
study drug 
c. Any investigational treatment for EFP on the buttock during the 12-month period 
before the injection of study drug 
d. Endermologie or similar treatments within a buttock during the 6-month period 
before injection of study drug 
e. Massage therapy within a buttock during the 3-month period before injection of study 
drug 
f. Creams (eg, Celluvera™, TriLastin®) and/or home therapies to prevent or mitigate 
EFP within a buttock during the 2-week period before injection of study drug 
5. Is presently nursing or providing breast milk 
6. Intends to become pregnant during the study 
7. Intends to initiate an intensive sport or exercise program during the study 
8. Intends to initiate a weight reduction program during the study 
9. Intends to use tanning spray or tanning booths during the study  
10. Has received an investigational drug or treatment within 30 days before injection of study 
drug 
11. Has a known systemic allergy to collagenase or any other excipient of study drug 
12. Has received any collagenase treatments at any time prior to treatment 

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13. Was a subject in a previous cellulite clinical trial of CCH: AUX-CC-830, AUX-CC-831, 
EN3835-102, EN3835-104, EN3835-201, EN3835-202, and/or EN3835-205 
14. Any other condition(s) that, in the Investigator’s opinion, might indicate the subject to be 
unsuitable for the study 
2.3. 
Selection of Target Buttock 
Upon confirmation of the two buttocks that are eligible for treatment (eligible criteria being each 
buttock have PR-PCSS and CR-PCSS scores of 3 or 4) on Day 1 prior to treatment 
randomization, the IWRS system will randomly assign one buttock as the target buttock in the 
background. The other (remaining) buttock will be considered the non-target buttock. The target 
buttock will be used for the primary efficacy endpoint. Subjects, investigators, site personnel and 
Endo personnel will be blinded to the target buttock assignment and will remain blinded until the 
clinical study database has been cleaned and locked. 
2.4. 
Selection of Dimples and Injection Sites During Treatment Visits 
2.4.1. 
Selecting and Marking the Dimples 
Selection of dimples to be treated in the two buttocks is at the discretion of the Investigator. 
Dimples must be well-defined and evident when the subject is standing in a consistent relaxed 
pose (without the use of any manipulation such as skin pinching or muscle contraction). Each 
subject will receive 3 treatment sessions of study drug in three visits, ie, Day 1, Day 22, and 
Day 43, according to randomization unless the buttock is dimple-free (score of 0 on CR-PCSS as 
reported by the Investigator); a dimple-free buttock does not preclude treatment of the 
contralateral buttock unless it is dimple-free also. During each treatment session, each of the 
buttocks will be photographed before and after marking dimples and injection sites while the 
subject is standing in a consistent relaxed pose as described in the Photography Manual. The 
cellulite severity assessments using the PR-PCSS and CR-PCSS will be completed prior to 
marking dimples and injection sites. 
The Investigator or qualified designee will select dimples within each buttock that are 
well-defined, evident when the subject is standing, and suitable for treatment; treatment consists 
of 12 injections per buttock (24 injections total in two buttocks) per session. Because the goal of 
treatment is to improve the aesthetic appearance of each entire buttock, the Investigator will be 
instructed to select dimples that in his or her opinion would most improve the aesthetic 
appearance of each entire buttock. The same dimples within a buttock or different dimples within 
a buttock may be treated at each session but injections must all be within the buttocks 
(12 injections per buttock) for all 3 sessions. Each buttock will receive all 3 treatment sessions 
unless the buttock has no treatable EFP dimples and the Investigator rates the buttock a score of 
0 on the CR-PCSS. If no injections in a particular buttock (right or left) are given at Treatment 
Session 2, subjects will still be assessed for treatment in the contralateral buttock at Treatment 
Session 2, and will return for the Day 43 visit and each of the buttocks will again be evaluated by 
the subject (PR-PCSS) and Investigator (CR-PCSS). If the Investigator rates either or both of the 
buttocks greater than 0 on the CR-PCSS, injections at Treatment Session 3 should be given. 

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2.4.2. 
Selecting Injection Sites 
For each dimple selected for treatment, the Investigator or qualified designee will choose 
injection sites (injection sites within a dimple should be spaced approximately 2 cm apart, if a 
dimple requires more than 1 injection; locating at least one injection site at the nadir, if present, 
of the dimple). Each injection site will be marked with a “dot” using a surgical marker. For 
round dimples, the “dot” will be placed in the center of the dimple; for elongated dimples, “dots” 
will be spaced out approximately 2 cm along the longer axis of the dimple. The Investigator or 
qualified designee will then use a surgical marker to circle each of the dimples selected for 
treatment. Circles in the buttock should not overlap.  
2.5. 
Randomization and Study Drug Administration 
2.5.1. 
Randomization 
If the 2 buttocks continue to meet eligibility criteria at Day 1, the subject will be eligible for 
randomization to study medication. Subjects will be randomized to EN3835 1.68 mg total dose 
(0.84 mg per buttock) or placebo in a 1:1 ratio. There will be approximately 210 subjects 
assigned to the EN3835 treatment group and 210 subjects assigned to the placebo group. 
Randomization of assigned treatment will be stratified by site using the interactive web response 
system (IWRS).  
2.5.2. 
Blinding and Unblinding 
This will be a double-blind study in which the investigator, study subject, and other study 
personnel involved in the evaluation of the subject efficacy and safety are blinded to the study 
drug treatment. The data vendor personnel in charge of the IWRS and the Endo personnel in 
charge of drug supply will be unblinded to study drug assignment, but will have no interaction 
with the subjects, investigators, clinical personnel, or study data.  
Unblinding of study treatment assignments will occur after all subjects have completed the study 
and the clinical study database has been cleaned and locked. Unblinding will occur by matching 
the kit numbers reported in the electronic case report form (eCRF) to the master list of kits in the 
IWRS. Any mistreatments will be reported as major protocol violations. In the case of a medical 
emergency, sites have the ability to determine treatment identification. If this occurs, the medical 
monitor will be notified immediately. 
2.5.3. 
Study Drug Administration 
At each treatment session, the site will request study drug kit numbers from the IWRS used for 
injections. For each of the two buttocks, the site personnel in charge of drug preparation will then 
reconstitute the study medication and prepare 4 syringes for study drug administration per 
buttock. The kit number, the number of injections given, and the number of dimples treated for 
each buttock will be recorded in the eCRF. The investigator will also indicate whether the 
subject received the injections per buttock as described in the protocol. If less than 12 injections 
are given for any buttock at any treatment session, the investigator is to indicate on the eCRF the 
number of injections and state the reason why fewer than 12 injections were given for that 
buttock. 

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2.6. 
Digital Photographs 
The investigator or qualified designee will photograph each buttock using a Sponsor-supplied 
standardized digital camera (Vectra, Canfield Scientific, Inc.) in a standardized manner. The 
subject will be standing for each photography session and will be wearing a standardized 
photographic garment as described in the Photography Manual. Each buttock will be 
photographed while the subject is standing in a consistent, relaxed standing pose, ie standing 
position with relaxed gluteus muscles, at the following time points: 
• Screening (no markings of dimples or injection site) - each of the two buttocks  
• Before and after marking dimples and injection sites (prior to injections) on Day 1, 
Day 22, and Day 43 - each of the two buttocks 
• During the Day 71 visit (end of study/early termination) (no dimple or injection site 
markings) - each of the two buttocks 
2.7. 
Patient Reported Photonumeric Cellulite Severity Scale (PR-PCSS) 
Subjects will rate the severity of their cellulite of each of their two buttocks at Screening and on 
Day 1, Day 22, Day 43, and Day 71 using the PR-PCSS. The PR-PCSS is a photonumeric scale 
ranging from 0 to 4. The following labels and descriptions are associated with each level of 
severity on the PR-PCSS:  
0: None: No evident cellulite 
1: Almost None: A few superficial dimples or ridges 
2: Mild: Several dimples or ridges of which most are superficial 
3: Moderate: Many dimples or ridges of which most are somewhat deep 
4: Severe: A lot of dimples or ridges of which many are deep covering most of the skin 
area 
Subjects will be instructed to sequentially look at each buttock under evaluation on a 
standardized 22” computer monitor and decide which of the images, labels, and descriptions on 
the PR-PCSS (mounted on a 10”×18” foam board) best match the severity of the cellulite in the 
scale. Subjects will be instructed that rating responses must be given in whole numbers; no half 
numbers are allowed. Subjects will be instructed to choose a PR-PCSS rating that is closest to 
their cellulite severity in the buttock being evaluated. Subjects will be instructed that if they 
consider the severity of the cellulite in the buttock is exactly halfway between 2 levels, to choose 
the more severe level. Subjects will enter their responses directly into an electronic data capture 
(EDC) system using a handheld tablet; the investigator and site personnel will be blinded to the 
rating entered by the subject. Each subject will have their own username and password to gain 
entry into the EDC system. The investigator and the investigator’s personnel will not have access 
to subject’s password. Once subjects have completed their evaluations for the visit, they will log 
out from the EDC system. 

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2.8. 
Clinician Reported Photonumeric Cellulite Severity Scale 
(CR-PCSS) 
Investigators will rate the severity of the cellulite of each of the two buttocks at Screening and on 
Day 1, Day 22, Day 43, and Day 71 using the CR-PCSS. The CR-PCSS mirrors the PR-PCSS in 
every manner except the descriptions.  
The following labels and descriptions are associated with each level of severity on the CR-PCSS 
Buttock scale:  
0: None: No dimples or evident cellulite 
1: Almost None: Few dimples that are mostly superficial in depth 
2: Mild: Several dimples of which most are shallow in depth 
3: Moderate: Many dimples of which most are moderate in depth 
4: Severe: A lot of dimples with some of more severe depth 
Investigators will be instructed to look at each buttock under evaluation ‘live’ with the subject 
standing in front of him/her. The investigator is to decide which of the images, labels and 
descriptions on the CR-PCSS (mounted on a 10”×18” foam board) best match the severity of the 
cellulite in the buttock. Investigators will be trained that responses must be given in whole 
numbers; no half numbers are allowed. Investigators will be trained that if they observe the 
cellulite in the buttock is exactly halfway between 2 levels, to choose the more severe level. 
Investigators will enter their responses directly into an EDC system using a handheld tablet. 
They will enter their username and password to gain access to the EDC system; the subject will 
not have access to view the investigator ratings. Investigators will be instructed not to verbalize 
their rating(s) or any opinion of the subject’s cellulite severity in order not to influence the 
subject. At each visit, the Investigator will make his/her assessment using the CR-PCSS 
independently and after the subject has conducted her self-assessment using the PR-PCSS 
Investigators will go through a training process and will need to pass a qualifying exercise prior 
to using the CR-PCSS. 
2.9. 
Patient Reported Cellulite Impact Scale (PR-CIS) 
The Patient Reported Cellulite Impact Scale is a 6-item static questionnaire; each item is 
answered by a subject on an 11-level numerical rating scale from 0 (equating to no impact but 
with wording specifically based on the question) to 10 (equating to extreme impact but with 
wording specifically based on the question) while viewing digital images of their buttocks at that 
visit. The PR-CIS items and their response options are listed below: 
 
 

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Please select the rating that best represents your answer on a scale of 0 to 10 with 0 
representing “Not at all” and 10 representing “Extremely”. Please answer each question. 
1. Thinking about the areas selected for treatment, how happy are you with the appearance of your cellulite? 
Not at all 
 
 
 
 
 
 
 
 
 
Extremely 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
2. Thinking about the areas selected for treatment, how bothered are you by the appearance of your cellulite? 
Not at all 
 
 
 
 
 
 
 
 
 
Extremely 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
3. Thinking about the areas selected for treatment, how self-conscious are you about the appearance of your 
cellulite? 
Not at all 
 
 
 
 
 
 
 
 
 
Extremely 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
4. Thinking about the areas selected for treatment, how embarrassed are you about the appearance of your 
cellulite? 
Not at all 
 
 
 
 
 
 
 
 
 
Extremely 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
5. Thinking about the areas selected for treatment, how much older do you look because of your cellulite? 
Not at all 
 
 
 
 
 
 
 
 
 
Extremely 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
6. Thinking about the areas selected for treatment, how overweight or out of shape do you look because of 
your cellulite? 
Not at all 
 
 
 
 
 
 
 
 
 
Extremely 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Subjects will be asked to answer the PR-CIS at Day 1 and Day 71 after they rate their cellulite 
severity on buttocks. Subjects will enter their responses to each of the 6 items directly into an 
EDC system using a handheld tablet.   
2.10. 
Subject Self-rating Scale (SSRS) 
The SSRS is a measure that assesses subject satisfaction with appearance in association with 
cellulite on the buttocks using whole numbers on a 7-level scale that ranges from 0 (extremely 
dissatisfied) to 6 (extremely satisfied). The patient will be asked to respond to the question 
related to the satisfaction with appearance of the cellulite on their buttocks on Day 1 and Day 71. 
No photographs or reference to previous ratings or evaluations will be used. Subjects will be 
given a list of responses and they will provide a rating from those below that best represents their 
answer (Table 2). 
Subjects will enter their responses directly into an EDC system using a handheld tablet. 

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Table 2: 
Subject Self-rating Scale (SSRS) 
Rating 
Response Option 
6 
Extremely Satisfied 
5 
Satisfied 
4 
Slightly satisfied 
3 
Neither satisfied nor dissatisfied 
2 
Slightly Dissatisfied 
1 
Dissatisfied 
0 
Extremely dissatisfied 
2.11. 
Global Assessment Ratings 
2.11.1. 
Subject Global Aesthetic Improvement Scale (S-GAIS) 
Subjects will complete the S-GAIS for each of the buttocks on Day 22, Day 43, and Day 71 
using the pre-treatment Day 1 image (Baseline) of the same buttock for comparison. Subjects 
will be asked to determine the degree of change seen in each buttock compared with how it 
looked before treatment on the following scale (Table 3). The subject will conduct the S-GAIS 
assessment after she completes her PR-CSS assessment to avoid introducing potential bias to the 
static PR-PCSS assessment. 
Table 3: 
Subject Global Aesthetic Improvement Scale (S-GAIS) 
Rating 
Response Option 
Description 
+3 
Very much improved 
My treated cellulite looks very much better. 
+2 
Much improved 
My treated cellulite looks much better, but additional treatment would 
slightly improve the result. 
+1 
Improved 
My treated cellulite looks better, but additional treatment is necessary. 
0 
No change 
My treated cellulite looks essentially the same as it did originally. 
−1 
Worse 
My treated cellulite looks worse than it did originally. 
−2 
Much worse 
My treated cellulite looks much worse than it did originally. 
−3 
Very much worse 
My treated cellulite looks very much worse than it did originally. 
Subjects will enter their responses directly into an EDC system using a handheld tablet. Subjects 
will be instructed not to reveal their responses to the investigators or site personnel and the 
investigators or site personnel will not have access to view subjects’ responses.  
2.11.2. 
Investigator Global Aesthetic Improvement Scale (I-GAIS) 
On Day 22, Day 43, and Day 71, the investigator will determine the degree of improvement of 
each of the buttocks by comparing the cellulite by live assessment on Day 22, Day 43, and 
Day 71 to the Day 1 pre-treatment (Baseline) image of that buttock (Table 4). The I-GAIS 
assessment will occur after the CR-PCSS assessment to avoid introducing potential bias to the 
static CR-PCSS assessment by the investigator at the site. The I-GAIS assessment will be 
conducted after the subject completes her assessments (PR-PCSS and/or S-GAIS). 

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Table 4: 
Investigator Global Aesthetic Improvement Scale (I-GAIS) 
Rating 
Response Option 
Description 
+3 
Very much improved 
Optimal cosmetic result from treatment of the treated dimples 
+2 
Much improved 
Marked improvement in the treated area appearance from before 
treatment, but not completely optimal 
+1 
Improved 
Obvious improvement in the treated area appearance from before 
treatment, but additional treatment is indicated 
0 
No change 
The treated area appearance is essentially the same as before treatment 
−1 
Worse 
The treated area appearance is worse than before treatment 
−2 
Much worse 
Marked worsening in appearance from the initial condition 
−3 
Very much worse 
Obvious worsening in appearance from the initial condition 
Investigators will enter their responses directly into an EDC system using a handheld tablet. The 
investigators will be instructed not to reveal their responses to the subjects and subjects will not 
have access to view the investigator ratings. 
2.11.3. 
Subject Satisfaction with Cellulite Treatment Assessment  
At the Day 71 visit, subjects will be asked to rate their overall satisfaction with the cellulite 
treatment on the two buttocks on the following scale (Table 5). 
Table 5: 
Subject Satisfaction with Cellulite Treatment Assessment - Buttocks 
Rating 
Description 
+2 
I am very satisfied with the cellulite treatment on my buttocks. 
+1 
I am satisfied with the cellulite treatment on my buttocks. 
0 
I am neither dissatisfied nor satisfied with the cellulite treatment on my buttocks. 
-1 
I am dissatisfied with the cellulite treatment on my buttocks. 
-2 
I am very dissatisfied with the cellulite treatment on my buttocks. 
Subjects will enter their responses directly into an EDC system using a handheld tablet.  
2.12. 
Skin Assessment (Fitzpatrick Scale) 
At the Screening visit, subject skin type will be evaluated by the Investigator using the 
Fitzpatrick Scale, shown in Table 6.  
Table 6: 
Fitzpatrick Scale 
I 
Pale white skin, blue/hazel eyes, blond/red hair 
Always burns, does not tan 
II 
Fair skin, blue eyes 
Burns easily, tans poorly 
III 
Darker white skin 
Tans after initial burn 
IV 
Light brown skin 
Burns minimally, tans easily 
V 
Brown skin 
Rarely burns, tans darkly easily 
VI 
Dark brown or black skin 
Never burns, always tans darkly 

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2.13. 
Weight, Height, and BMI 
At the Screening visit, height and weight measurements will be taken. Baseline body mass index 
(BMI) will be computed from these measurements as the weight in kilograms (kg) divided by 
height in meters squared (m2). Body weight will also be measured at the Day 22, Day 43, and 
Day 71 visits; BMI will be computed from each of these measurements using the height at 
screening. 
2.14. 
Adverse Events 
Medically significant changes that occur after enrollment into this study will be recorded as 
adverse events (AEs). 
The following information will be collected for all AEs:  
• Verbatim description  
• Date of Onset 
• Date of Resolution/or Ongoing 
• Severity (Mild, Moderate, Severe) 
• Relationship to Study Drug (Not Related, Unlikely Related, Possibly Related, 
Probably Related) 
• Action taken with study drug (None, Drug Interrupted, Drug Withdrawn) 
• Outcome (Recovered/Resolved, Recovered/Resolved w/Sequelae, Recovering/ 
Resolving, Not Recovered/Not Resolved, Fatal, Unknown) 
• Whether the AE led to study discontinuation 
• Whether or not a concomitant medication or procedure was required 
• Classified as a serious adverse event (SAE) or not 
• SAE Code (Death, Life-threatening, Inpatient or prolonged hospitalization, Persistent 
or significant disability/incapacity, Congenital anomaly or birth defect, Other 
medically important event) 
• Designation of an AE of Special Interest: AEs including bruising, ecchymosis, 
hematomas, and contusions that occur remote to the site of drug administration, or 
any hypersensitivity reactions, including anaphylaxis, will be recorded as an AE of 
special interest and reported as an AE or SAE as appropriate. In addition, local 
adverse events associated with the injection site, including bruising, pain, 
nodules/mass, ulceration, erythema, pruritus, swelling, and/or induration, will be 
recorded and evaluated for seriousness and severity 

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2.15. 
Medical History 
A medical history of the subject will be taken during the screening period. The onset and 
resolution date or ongoing will be recorded for each condition reported. If no part (including 
year) of the onset or resolution date is known, then the condition will be reported as occurring 
less than 5 years ago or more than or equal to 5 years ago.  
Medical history will also include a report of tobacco and alcohol use. For each item subjects are 
to report whether they never used, are currently using, or have formerly used. If subjects are a 
current or former user, they are to indicate the number of years they used the product, and former 
users are to indicate the stop date of using the product. 
For reproductive history, subjects are to indicate the date of their last menstrual period and the 
number of pregnancies they have had. 
2.16. 
Edematous Fibrosclerotic Panniculopathy Disease History 
During the screening period an EFP disease history will be obtained from the subject. The EFP 
disease history will include onset date of EFP symptoms, previous treatments used for EFP, and 
family history of cellulite, answered as yes, no, or unknown for any family relation.  
2.17. 
Physical Examination 
During the screening period, the investigator will perform a physical examination (by body 
system) on each subject. Any abnormalities will be described.  
2.18. 
Vital Signs 
Blood pressure (systolic/diastolic), respiratory rate, pulse rate, and body temperature will be 
assessed at each study visit. On injection days, blood pressure, respiratory rate, and pulse rate 
will be measured prior to the injections (up to 4 hours prior to the injection), and at 15 and 
30 minutes after the injection. If at the 30-minute measurement, the vital signs are not stable, 
subjects will be required to remain at the site until all the vital signs are stable. The investigator 
will record only the last vital sign measurement prior to discharge. On injection days, body 
temperature will be taken only prior to the injection, at the 30-minute post-dose measurement, 
and, if necessary, at the prior to discharge measurement. On injection days, the time the vital 
signs are taken will also be recorded. 
2.19. 
12-Lead Electrocardiogram 
During the screening period, subjects will have a resting 12-lead ECG. A qualified physician will 
assess the ECG as normal, abnormal not clinically significant, or abnormal clinically significant. 
The investigator or qualified designee must sign and date the ECG, thereby acknowledging 
review of the ECG results. The investigator will be able to record any comments regarding the 
ECG, including explaining any abnormal findings or providing details if the ECG was not done 
per protocol. 

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2.23. 
Concomitant Medications 
Any medications (prescription or over-the-counter) used during the study or within 90 days prior 
to randomization will be recorded. Any prior medications used for EFP/cellulite should be 
reported. Included will be: 
• Verbatim name of medication 
• Medication start date 
• Medication end date or ongoing 
• Dose, units, frequency, and route of medication 
• Reason for medication (medical history, AE, prophylaxis, health maintenance, 
EFP/cellulite, birth control, or other) 
Additional space is available for comments regarding reason for medication, units, route, and 
frequency. 
2.24. 
Concomitant Procedures/Therapies 
Any procedures or therapies used during the study will be recorded. Any prior procedures for 
EFP/Cellulite or birth control should be reported. Included will be: 
• Verbatim description of the procedure 
• Start date 
• End date or ongoing 
• Reason for procedure (medical history, AE, prophylaxis, health maintenance, 
EFP/cellulite, birth control, or other) 
Additional space is available for comments regarding reason for procedure. 
3. 
STUDY PARAMETERS 
3.1. 
Subject Disposition 
Subjects will be considered as completing the study (ie, completers) if they complete the Day 71 
visit. Subjects who do not complete the study will report their reason for early discontinuation. 
Time in the study (days) will be computed as the date of last visit minus the date of Day 1 + 1, 
where the date of the last visit is determined as the following: 
• The date of Day 71 if the subject completes the study 
• The date of early termination visit if the subject is terminated early from study at a 
non-scheduled visit 
• The date of the latest scheduled visit if the subject is terminated early from study at a 
scheduled visit or lost to follow-up 

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3.2. 
Number of Treatment Sessions 
A treatment session will be counted as given overall if at that treatment session a subject receives 
at least 1 injection of study drug in either or both of the buttocks. Total number of treatment 
sessions overall received will be calculated. 
For each of the buttocks (target or non-target buttock), subjects who receive at least 1 injection 
of study medication on Day 1, Day 22, or Day 43 will be counted as having a treatment session. 
Subjects will be classified into cohorts by buttock based on the number of treatment sessions 
they have. The reason why a treatment session was not done will be obtained and classified into 
one of the following: 
• Early termination prior to visit 
• Visit not done 
• Visit done but no injections given due to no evident cellulite 
• Visit done but no injections given due to AE 
• Visit done but no injections given due to other reasons 
If a treatment session was done, subjects will be classified into one of the following per 
treatment sessions: 
• 12 injections per buttock given 
• Less than 12 injections per buttock given due to not enough evident dimples 
• Less than 12 injections per buttock given due to AE 
• Less than 12 injections per buttock given due to other reasons 
3.3. 
Early Termination Visit Assessments 
Subjects who discontinue early will have all Day 71 procedures and assessments completed at an 
early termination visit. Those assessments and measurements will not be used for the observed 
data analysis at Day 71 but for the Day 71 (last observation carried forward [LOCF]) analysis. 
3.4. 
Treatment Groups 
Subjects will be divided into 1 of 2 treatment groups based on their randomization. The 
2 treatment groups will be referred to as: 
• EN3835 1.68 mg total dose (0.84 mg per buttock) 
• Placebo  
These group assignments will remain regardless of the actual dose or type of study medication 
received. Subjects who receive a different dose or different study medication at any of the 
treatment sessions (due, for example, to a pharmacy error) from the treatment to which they were 
randomized will be summarized within their randomized group unless explicitly specified. These 
subjects will also be reported as a protocol deviation.  

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3.5. 
Efficacy Parameters 
3.5.1. 
PR-PCSS 
3.5.1.1. 
Baseline PR-PCSS Rating 
For each buttock (target or non-target), the baseline PR-PCSS rating will be based on the 
subject’s PR-PCSS evaluation done at Day 1. If no evaluation is done for a buttock on Day 1 
(eg, done using an incorrect digital image), the rating of the subject’s PR-PCSS for that buttock 
at Screening will be used for the baseline. 
3.5.1.2. 
Change from Baseline PR-PCSS Rating 
For each buttock (target or non-target), the change from baseline PR-PCSS rating will be the 
visit rating minus the baseline rating. A more negative change in rating indicates a greater 
improvement of cellulite severity in that buttock. 
3.5.1.3. 
Subject PR-PCSS Responders for Target Buttock 
A 2-level PR-PCSS responder for the target buttock is defined as a subject with an improvement 
in the PR-PCSS rating of at least 2 levels from baseline (ie, change from baseline PR-PCSS 
rating of -2, -3, or -4) on the target buttock.  
A 1-level PR-PCSS responder for the target buttock is defined as a subject with an improvement 
in the PR-PCSS rating of at least 1 level from baseline (ie, change from baseline PR-PCSS rating 
of -1, -2, -3, or -4) on the target buttock at an evaluation time point.  
3.5.1.4. 
Subject PR-PCSS Responders for Non-target Buttock 
A 2-level PR-PCSS responder for the non-target buttock is defined as a subject with an 
improvement in the PR-PCSS rating of at least 2 levels from baseline (ie, change from baseline 
PR-PCSS rating of -2, -3, or -4) on the non-target buttock.  
A 1-level PR-PCSS responder for the non-target buttock is defined as a subject with an 
improvement in the PR-PCSS rating of at least 1 level from baseline (ie, change from baseline 
PR-PCSS rating of -1, -2, -3, or -4) on the non-target buttock at an evaluation time point.  
3.5.1.5. 
PR-PCSS Responders for at Least One Buttock 
A 1-level PR-PCSS responder for at least one buttock is defined as a subject who is a 1-level 
PR-PCSS responder (as defined previously, this is a subject with at least a 1-level improvement 
in PR-PCSS from baseline rating) for either the target buttock or the non-target buttock or both 
buttocks at an evaluation time point. 
A 2-level PR-PCSS responder for at least one buttock is defined as a subject who is a 2-level 
PR-PCSS responder for either the target buttock or the non-target buttock or both buttocks at an 
evaluation time point. 
3.5.1.6. 
PR-PCSS Responders for Two Buttocks 
A 1-level PR-PCSS responder for the two buttocks in the same individual subject is defined as a 
subject who is a 1-level PR-PCSS responder for both buttocks at an evaluation time point. 

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A 2-level PR-PCSS responder for the two buttocks in the same individual subject is defined as a 
subject who is a 2-level PR-PCSS responder for both buttocks at an evaluation time point. 
3.5.2. 
S-GAIS 
3.5.2.1. 
S-GAIS Rating 
The S-GAIS rating is directly obtained from the subject’s assessments of each buttock (target or 
non-target) at an evaluation visit. 
3.5.2.2. 
S-GAIS Responders for Target Buttock 
A 1-level S-GAIS responder for the target buttock is defined as a subject with S-GAIS rating of 
at least 1 (ie, 1, 2 or 3) on the target buttock at an evaluation time point.  
A 2-level S-GAIS responder for the target buttock is defined as a subject with S-GAIS rating of 
at least 2 (ie, 2 or 3) on the target buttock at an evaluation time point.  
3.5.2.3. 
S-GAIS Responders for Non-target Buttock 
A 1-level S-GAIS responder for the non-target buttock is defined as a subject with S-GAIS 
rating of at least 1 (ie, 1, 2 or 3) on the non-target buttock at an evaluation time point. 
A 2-level S-GAIS responder for the non-target buttock is defined as a subject with S-GAIS 
rating of at least 2 (ie, 2 or 3) on the non-target buttock at an evaluation time point. 
3.5.2.4. 
S-GAIS Responders for at Least One Buttock 
A 1-level S-GAIS responder for at least one buttock is defined as a subject who is a 1-level 
S-GAIS responder for either the target buttock or the non-target buttock or both buttocks at an 
evaluation time point. 
3.5.2.5. 
S-GAIS Responders for Two Buttocks 
A 1-level S-GAIS responder for the two buttocks in the same individual subject is defined as a 
subject who is a 1-level S-GAIS responder for both buttocks at an evaluation time point. 
3.5.3. 
PR-CIS 
The PR-CIS total score will be the sum of the six items on the scales. Item #1 on the PR-CIS 
asking how happy the subject is about their appearance of cellulite will be reversed by 
subtracting the subject’s reported assessment from 10 (ie, for purposes of the composite, scoring 
for the “happy” question was reversed (reflected) to make it directionally consistent with the 
other questions). In this manner, a higher number on six of the PR-CIS questions will reflect a 
more negative impact. The PR-CIS total score can range from 0 to 60 with higher numbers 
reflecting more negative impact from the cellulite.  If scores on two or less of the 6 items are 
missing, the PR-CIS total score will be computed as the mean of the answered items times 6. If 
scores on three or more of the six items are missing, then the PR-CIS total score will be set to 
missing. 

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Similarly, the PR-CIS abbreviated total score will be the sum of the five items (Items #1-4 and 
Item #6) on the scale (note that for the abbreviated total score Item #1 score should be replaced 
by subtracting the item score from 10). The PR-CIS abbreviated total score can range from 0 to 
50 with higher numbers reflecting more negative impact from the cellulite. If scores on two or 
less of the 5 items are missing, the PR-CIS abbreviated total score will be computed as the mean 
of the answered items times 5. If scores on three or more of the five items are missing, then the 
PR-CIS abbreviated total score will be set to missing. 
3.5.3.1. 
Baseline PR-CIS Item Scores 
Baseline PR-CIS score for each individual item will be based on the subject’s response to the 
item at Day 1. 
3.5.3.2. 
Change from Baseline PR-CIS Item Scores 
The change from baseline PR-CIS item score will be the visit score minus the baseline score. For 
Item #1, a more positive change in score indicates a greater improvement of impact of the 
cellulite on subject’s happiness while for other items a more negative change in score indicates a 
greater reduction of impact of the cellulite on subject’s life. 
3.5.3.3. 
Responders Based on PR-CIS Item Scores 
A PR-CIS responder for each item is defined as a subject with a reduction in the PR-CIS total 
score of at least 2 from baseline at an evaluation time point. 
3.5.3.4. 
Baseline PR-CIS Total Scores 
Baseline PR-CIS total score will be based on the subject’s PR-CIS total score at Day 1. 
3.5.3.5. 
Change from Baseline PR-CIS Total Scores 
The change from baseline PR-CIS total score will be the visit total score minus the baseline total 
score. A more negative change in score indicates a greater reduction of impact of the cellulite on 
subject’s life. 
3.5.3.6. 
Responders Based on PR-CIS Total Score 
For PR-CIS total score, a PR-CIS responder is defined as a subject with a reduction in the 
PR-CIS total score of at least 12 from baseline (ie, average of at least 2 for each item) at an 
evaluation time point. 
3.5.3.7. 
Baseline PR-CIS Abbreviated Total Scores 
Baseline PR-CIS abbreviated total score will be based on the subject’s PR-CIS abbreviated total 
score at Day 1. 
3.5.3.8. 
Change from Baseline PR-CIS Abbreviated Total Scores 
The change from baseline PR-CIS abbreviated total score will be the visit abbreviated total score 
minus the baseline abbreviated total score. A more negative change in score indicates a greater 
reduction of impact of the cellulite on subject’s life. 

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3.5.3.9. 
Responders Based on PR-CIS Abbreviated Total Scores 
For PR-CIS abbreviated total score, a PR-CIS responder is defined as a subject with a reduction 
in the PR-CIS total score of at least 10 from baseline (ie, average of at least 2 for each item) at an 
evaluation time point. 
3.5.4. 
SSRS 
3.5.4.1. 
SSRS Rating Scores 
The subject SSRS rating score is directly obtained from the subject’s assessments of a region, 
ie, two buttocks, at baseline (Day 1) and the Day 71/early termination visit. 
3.5.4.2. 
Subject 1-Level SSRS Responders 
A 1-Level SSRS responder is defined as a subject with at least slightly satisfied (ie, slightly 
satisfied [4], very satisfied [5] or extremely satisfied [6]) with her appearance of the cellulite on 
her buttocks at Day 71/early termination visit. 
3.5.5. 
Subject Global Satisfaction With Cellulite Treatment 
3.5.5.1. 
Subject Global Satisfaction With Cellulite Treatment Rating 
The subject global satisfaction with cellulite treatment rating is directly obtained from the 
subject’s assessments of a region, ie, two buttocks, at the Day 71/early termination visit. 
3.5.5.2. 
Subject-satisfied Responders 
Subject-satisfied responder is defined as subjects with a response of “Satisfied” or “Very 
Satisfied” in the subject satisfaction with cellulite treatment assessment at Day 71/early 
termination visit. 
3.5.6. 
CR-PCSS 
3.5.6.1. 
Investigator Baseline CR-PCSS Rating 
For each buttock (target or non-target), investigator baseline CR-PCSS rating will be based on 
the investigator’s CR-PCSS evaluation done at Day 1.  
3.5.6.2. 
Investigator Change from Baseline CR-PCSS Rating 
For each buttock (target or non-target), the investigator change from baseline CR-PCSS rating 
will be the investigator visit rating minus the investigator baseline rating at an evaluation time 
point. A more negative change from baseline indicates a greater improvement of cellulite 
severity in that buttock. 
3.5.6.3. 
CR-PCSS Responders for Target Buttock 
A 2-level CR-PCSS responder for the target buttock is defined as a subject with an improvement 
in the CR-PCSS rating of at least 2 levels from baseline (ie, change from baseline CR-PCSS 
rating of -2, -3, or -4) on the target buttock at an evaluation time point. 

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A 1-level CR-PCSS responder for the target buttock is defined as a subject with an improvement 
in the CR-PCSS rating of at least 1 level from baseline (ie, change from baseline CR-PCSS 
rating of -1, -2, -3, or -4) on the target buttock at an evaluation time point. 
3.5.6.4. 
CR-PCSS Responders for Non-target Buttock 
A 2-level CR-PCSS responder for the non-target buttock is defined as a subject with an 
improvement in the CR-PCSS rating of at least 2 levels from baseline (ie, change from baseline 
CR-PCSS rating of -2, -3, or -4) on the non-target buttock at an evaluation time point. 
A 1-level CR-PCSS responder for the non-target buttock is defined as a subject with an 
improvement in the CR-PCSS rating of at least 1 level from baseline (ie, change from baseline 
CR-PCSS rating of -1, -2, -3, or -4) on the non-target buttock at an evaluation time point. 
3.5.6.5. 
CR-PCSS Responders for at Least One Buttock 
A 1-level CR-PCSS responder for at least one buttock is defined as a subject who is a 1-level 
CR-PCSS responder for either the target buttock or the non-target buttock or both buttocks at an 
evaluation time point. 
A 2-level CR-PCSS responder for at least one buttock is defined as a subject who is a 2-level 
CR-PCSS responder for either the target buttock or the non-target buttock or both buttocks at an 
evaluation time point. 
3.5.6.6. 
CR-PCSS Responders for Two Buttocks 
A 1-level CR-PCSS responder for the two buttocks in the same individual subject is defined as a 
subject who is a 1-level CR-PCSS responder for both the target and non-target buttocks at an 
evaluation time point. 
A 2-level CR-PCSS responder for the two buttocks in the same individual subject is defined as a 
subject who is a 2-level CR-PCSS responder for both the target and non-target buttocks at an 
evaluation time point. 
3.5.7. 
I-GAIS 
3.5.7.1. 
I-GAIS Rating 
The I-GAIS rating is directly obtained from the investigator’s assessments at an evaluation visit.  
3.5.7.2. 
I-GAIS Responders for Target Buttock 
A 1-level I-GAIS responder for the target buttock is defined as a subject with I-GAIS rating of at 
least 1 (ie, 1, 2, or 3) on the target buttock at an evaluation time point.  
3.5.7.3. 
I-GAIS Responders for Non-target Buttock 
A 1-level I-GAIS responder for the non-target buttock is defined as a subject with I-GAIS rating 
of at least 1 (ie, 1, 2, or 3) on the non-target buttock at an evaluation time point.  

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3.5.7.4. 
I-GAIS Responders for at Least One Buttock 
A 1-level I-GAIS responder for at least one buttock is defined as a subject who is a 1-level 
I-GAIS responder for either the target buttock or the non-target buttock or both buttocks at an 
evaluation time point. 
3.5.7.5. 
I-GAIS Responders for Two Buttocks 
A 1-level I-GAIS responder for the two buttocks in the same individual subject is defined as a 
subject who is a 1-level I-GAIS responder for both the target and non-target buttocks at an 
evaluation time point. 
3.5.8. 
Subject (PR-PCSS)/Investigator (CR-PCSS) Composite Responders 
3.5.8.1. 
Composite Responders for Target Buttock 
For each visit (Day 22, Day 43, and Day 71), the subject PR-PCSS responder classification and 
investigator CR-PCSS responder classification for the target buttock will be used to compute the 
composite responder classification for that buttock. If the classification is missing for 1 or both 
components (ie, the PR-PCSS component or the CR-PCSS component), then the composite 
responder classification is missing for that visit. 
A 2-level composite responder for the target buttock is defined as any subject who is both a 
2-level PR-PCSS responder and a 2-level CR-PCSS responder for the target buttock. If the 
subject is a 2-level responder on 1 component but not on the other or on neither component for 
the target buttock, then the subject will be classified as a 2-level non-composite responder for the 
target buttock.  
A 1-level composite responder for the target buttock is defined as any subject who is both a 
1-level PR-PCSS responder and a 1-level CR-PCSS responder for the target buttock. If the 
subject is a 1-level responder on 1 component but not on the other or on neither component for 
the target buttock, then the subject will be classified as a 1-level non-composite responder for the 
target buttock.  
3.5.8.2. 
Composite Responders for Non-target Buttock 
For each visit (Day 22, Day 43, and Day 71), the subject PR-PCSS responder classification and 
investigator CR-PCSS responder classification for the non-target buttock will be used to compute 
the composite responder classification for that buttock. If the classification is missing for 1 or 
both components, then the composite responder classification is missing for that visit. 
A 2-level composite responder for the non-target buttock is defined as any subject who is both a 
2-level PR-PCSS responder and a 2-level CR-PCSS responder for the non-target buttock. If the 
subject is a 2-level responder on 1 component but not on the other or on neither component for 
the non-target buttock, then the subject will be classified as not a “2-level composite responder 
for the non-target buttock”.  

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A 1-level composite responder for the non-target buttock is defined as any subject who is both a 
1-level PR-PCSS responder and a 1-level CR-PCSS responder for the non-target buttock. If the 
subject is a 1-level responder on 1 component but not on the other or on neither component for 
the non-target buttock, then the subject will be classified as not a “1-level composite responder 
for the non-target buttock”.  
3.5.8.3. 
Composite Responders for at Least One Buttock 
A 2-level composite responder for at least one buttock is defined as any subject who is a 2-level 
composite responder for the target buttock or the non-target buttock or both buttocks; otherwise 
the subject will be defined as not a “2-level composite responder for at least one buttock”.  
A 1-level composite responder for at least one buttock is defined as any subject who is a 1-level 
composite responder for the target buttock or the non-target buttock or both buttocks; otherwise 
the subject will be defined as not a “1-level composite responder for at least one buttock”.  
3.5.8.4. 
Composite Responders for Two Buttocks 
A 2-level composite responder for the two buttocks in the same individual subject is defined as 
any subject who is a 2-level composite responder for both the target buttock and the non-target 
buttock; otherwise the subject will be defined as not a “2-level composite responder for the two 
buttocks”.  
A 1-level composite responder for the two buttocks in the same individual subject is defined as 
any subject who is a 1-level composite responder for both the target buttock and the non-target 
buttock; otherwise the subject will be defined as not a “1-level composite responder for the two 
buttocks”.  
3.6. 
Safety Parameters 
3.6.1. 
Adverse Events 
Adverse events will be mapped to preferred term using the Medical Dictionary for Regulatory 
Activities (MedDRA). Treatment-emergent adverse events (TEAEs) are any AEs with a start 
date equal to or after the date of the first injection. Treatment-related AEs are any AEs with a 
relationship of possibly or probably related to study medication or AEs with a missing 
relationship. 
3.6.1.1. 
Adverse Event Treatment Session 
An AE’s association with a treatment session will be based on the start date of the AE compared 
to the date of the injection. Adverse events with a start date between the Day 1 visit date and the 
day prior to the next dose or, if no further dose, the last visit date in the study will be associated 
with Treatment Session 1. If study drug is administered at the Day 22 visit, AEs with a start date 
between the Day 22 visit date and the day prior to the next dose or, if no further dose, the last 
visit date in the study will be associated with Treatment Session 2. If study drug is administered 
at the Day 43 visit, AEs with a start date between the Day 43 visit date and the Day 71 visit date 
will be associated with Treatment Session 3.  

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3.6.1.2. 
Adverse Event Duration 
Duration of an AE will be the AE end date minus the AE start date + 1. If AEs are still ongoing 
at the end of the study or AEs have partial start or stop dates, durations of those AEs are not 
determined. 
The duration of AEs will be used to determine the categories of AE durations (1-4 days, 
5-7 days, 8-14 days, 15-21 days, and >21 days). For ongoing AEs, the category of AE duration 
will be missing unless those events have an onset date 21 days prior to the subject’s last visit in 
the study. In this case, the category of the AE duration will be classified as “>21 days”. 
3.6.2. 
Vital Signs and Clinical Laboratories 
3.6.2.1. 
Baseline Values and Change from Baseline Values 
The baseline values for vital signs (study baseline) and clinical laboratories will be the last 
available measurement prior to the first dose of study medication. For clinical laboratories this 
could be the screening value or it could be an unscheduled lab, if the unscheduled lab is the 
closest value preceding the first injection. For vital signs, baseline will be those taken at Day 1 
predose for the by-visit analyses. 
Vital signs will additionally be analyzed on each injection day. For each injection day, baseline 
(injection day baseline) will be a predose value taken on that day.  
Change from baseline will be the visit/time point value minus the baseline value. 
3.6.2.2. 
Sponsor-defined Potentially Clinically Important Laboratory Values 
Table 8 presents the criteria for determining potentially clinically important (PCI) laboratory 
values. 
Table 8: 
Sponsor-defined Potentially Clinically Important Laboratory Criteria 
Analyte 
PCI Low: Less than or equal to 
PCI High: Greater than or equal to 
Hemoglobin (g/L) 
100 
190 
Hematocrit  
0.3 
0.6 
Platelets (109/L) 
100 
650 
ALT (U/L) 
 
3×ULN 
AST (U/L) 
 
3×ULN 
Creatinine (μmol/L) 
 
300 
BUN (mmol/L)  
 
12 
ALT=Alanine aminotransferase; AST=Aspartate aminotransferase; BUN=Blood urea nitrogen; PCI=Potentially 
clinically important; ULN=Upper limit of normal 
3.6.2.3. 
Sponsor-defined Potentially Clinically Important Vital Sign Values 
Table 9 presents the criteria (using study baseline) for determining PCI vital sign values. 

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Table 9: 
Sponsor-defined Potentially Clinically Important Vital Sign Criteria 
Parameter 
PCI Low 
PCI High 
Systolic blood pressure 
≤90 mm Hg and decrease ≥20 mm Hg 
from baseline 
≥180 mm Hg and increase ≥20 mm Hg 
from baseline 
Diastolic blood pressure 
≤50 mm Hg and decrease ≥15 mm Hg 
from baseline 
≥105 mm Hg and increase ≥15 mm Hg 
from baseline 
Pulse rate 
≤50 bpm and decrease ≥15 bpm from 
baseline 
≥120 bpm and increase ≥15 bpm from 
baseline 
Respiratory rate 
≤8 brpm and decrease ≥7 brpm from 
baseline 
≥25 brpm and increase ≥7 brpm from 
baseline 
Temperature 
 
≥38.3°C and increase ≥1.1°C from 
baseline 
bpm=Beats per minutes; brpm=Breaths per minute; PCI=Potentially clinically important 
3.7. 
Other Parameters 
3.7.1. 
Immunogenicity 
Seropositivity and titer levels for both anti-AUX-I and anti-AUX-II antibodies individually will 
be determined from each analyzed sample. Samples with a positive titer value will undergo a log 
transformation for analyses. Samples with a titer level less than 1 will be assigned or imputed as 
a log transformed titer of zero (0) for statistical analyses.  
Samples to be assayed for neutralizing antibodies for AUX-I and AUX-II will be obtained from a 
subset of seropositive binding antibodies samples on Day 1 and Day 71 (see section 2.22). 
Samples will be classified as positive or negative for neutralizing antibodies based on the results 
of these assays. 
3.7.2. 
Medical History 
Medical history will be mapped to preferred term using MedDRA. Subjects with medical 
histories of Dupuytren’s disease, Ledderhose’s disease, knuckle pads, diabetes, and epilepsy will 
be summarized. Subjects will be coded as having these disorders based on the preferred term of 
their reported medical histories. Knuckle pads will also include the preferred term of ‘Garrod 
pads’. Ledderhose’s disease will also include the preferred term of ‘fibromatosis’. Epilepsy will 
also include the preferred term of ‘convulsion’. Diabetes will include the preferred terms of 
‘diabetes mellitus’, ‘type 1 diabetes mellitus’, or ‘type 2 diabetes mellitus’. Diabetes will not 
include subjects who report ‘glucose tolerance impaired’ (borderline diabetes or pre-diabetes), 
‘diabetic vascular disorder’ or ‘blood glucose increased’. All medical history terms will be 
reviewed by the study medical monitor to determine if any other terms should be included in the 
summary. 
Age at EFP symptoms onset will be computed as the date of the EFP symptoms reported on the 
medical history eCRF minus the date of birth divided by 365.25. If the date of EFP symptom 
onset is incomplete, the date will be imputed according to the rules set up in section 6.2.2. 

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3.7.3. 
Prior/Concomitant Medications 
All medications will be coded with the World Health Organization (WHO) drug dictionary. A 
concomitant medication is any medication with a stop date on or after the date of the first 
injection or the medication is reported as ongoing. A prior medication is any medication with a 
stop date prior to the date of the first injection. 
3.7.4. 
Prior EFP Treatment 
Prior EFP treatment will be obtained from the prior/concomitant medication and prior/ 
concomitant procedure pages of the eCRF. If on either of these pages a medication or treatment 
is reported with the indication ‘EFP/cellulite’ with a start date prior to the first dose of study 
medication, then the medication or procedure will be considered a prior EFP treatment. All 
medications will be classified as EFP drug. All procedures will be classified into one of the 
following groups: 
• Liposuction 
• Laser treatments 
• Surgery (subcision or powered subcision) 
• Massage 
• Radiofrequency 
• Mesotherapy (including injections) 
• Cryolipolysis 
• Buttock implant treatment 
• Cream 
• Other 
The classification will be reviewed and approved by the study medical monitor. Any EFP 
treatment used after the Day 1 visit will be noted and reported as a protocol violation. 
Time since the last EFP treatment will be computed as the date of the most recent EFP treatment 
minus the date the informed consent was signed divided by 365.25. If the date of any EFP 
treatments is incomplete, the date will be imputed according to the rules set up in section 6.2.2. 
4. 
ANALYSIS POPULATIONS 
4.1. 
Safety Population 
The safety population is defined as all enrolled subjects who have at least 1 injection of study 
medication. All safety parameters will be summarized based on this population.  

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4.2. 
Intent-to-Treat (ITT) Population 
The ITT population is defined as all randomized subjects who have at least 1 injection of study 
medication. All demographic and baseline characteristic summaries will be based on this 
population. The primary and key secondary efficacy parameters will be summarized based on 
this population.  
4.3. 
Modified Intent-to-Treat (mITT) Population 
The mITT population is defined as all ITT subjects with a baseline and at least 1 post-injection 
evaluation of both the investigator CR-PCSS and subject PR-PCSS for both the target and 
non-target buttocks. All efficacy evaluations will be analyzed based on the mITT population. 
4.4. 
Per-Protocol (PP) Population  
The PP population is defined as a subset of the mITT population who are considered compliant 
with the protocol to ensure the efficacy analysis most closely reflects the scientific model 
underlying the protocol.(1) 
Study subjects will be excluded from the PP population if they meet any of the following criteria:  
• Placebo randomized subject who receives EN3835 treatment 
• EN3835 randomized subject who receives placebo treatment only throughout study 
• Any subject who receives protocol-prohibited medications 
• Subject missing PR-PCSS and/or CR-PCSS assessment at Day 71 
• Subject with a buttock not receiving all three treatment sessions without medical 
reasons (eg, adverse events or CR-PCSS rated as zero (0)) 
• Subject who did not meet all inclusion and exclusion criteria 
If more than 10% of the mITT population subjects are excluded from the PP population, then all 
efficacy summaries will be repeated for the PP population. All protocol violations, major and 
minor, will be listed.  
5. 
STATISTICAL METHODS 
5.1. 
Overview 
The primary efficacy endpoint will be summarized as percentages and analyzed using a CMH 
test that compares the 2 treatment groups and adjusts for analysis center at a level of significance 
of 0.05 based on the ITT population. Any subject who does not have an evaluation of either 
CR-PCSS or PR-PCSS at Day 71 will be classified as a non-responder.  
The key secondary efficacy endpoints except for change from baseline in the PR-CIS total score 
at Day 71 will be summarized as percentages and analyzed using a CMH test that compares the 
2 treatment groups and adjusts for analysis center based on the ITT population. Any subject who 
does not have an evaluation or assessment at Day 71 will be classified as a non-responder. The 
change from baseline in the PR-CIS total score at Day 71 will be summarized using descriptive 

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statistics (n, mean, standard deviation (SD), median, minimum and maximum) and analyzed by 
ANCOVA with a factor of treatment group and analysis center adjusting for baseline value. The 
key secondary efficacy Family #1 analyses will be performed only if the primary efficacy 
analysis is significant at a significance level of p ≤ 0.05. Similarly key secondary efficacy 
Family #2 analyses will be performed only if at least one of four key secondary efficacy 
Family #1 endpoints is significant at a significance level of p ≤ 0.0125 and key secondary 
efficacy Family #3 analyses will be performed only if at least one of two key secondary efficacy 
Family #2 endpoints is significant at a significance level of unused alpha from Family #1 divided 
by 2. Any subject who does not have a PR-CIS evaluation or assessment at Day 71 will be 
imputed as baseline value for the analysis. Within a family of key secondary efficacy endpoints a 
Bonferroni procedure will be performed to assure an overall type I error rate of no more 
than 0.05. 
All supportive efficacy endpoints will be summarized as percentages. All the supportive analyses 
are performed based on the observed data only at all the visits in the mITT population without 
multiplicity adjustment. An additional analysis will be performed at Day 71 with missing data at 
Day 71 handled by an LOCF approach if subjects have at least one post-dose evaluation. If a 
subject does not have any post-dose evaluation, analysis value will be missing (not imputed). 
The dichotomous secondary endpoints (ie, responder endpoints) will be analyzed using a CMH 
test adjusted for analysis center. Changes in the PR-PCSS ratings and CR-PCSS ratings from 
baselines, S-GAIS ratings, and I-GAIS ratings will be analyzed using the Wilcoxon rank sum 
test. Changes from baselines in PR-CIS individual items, total scores or abbreviated total scores 
will be analyzed using the analysis of covariance (ANCOVA) adjusted for baseline values. 
The AE endpoints will be summarized as count and percentages by preferred term and by 
treatment group and p values will be obtained from the Fisher exact test to test treatment 
difference of incidence. The change from baseline for vital signs and clinical laboratory 
parameters are compared between EN3835 and placebo using an analysis of variance (ANOVA) 
with a factor of drug (EN3835 or placebo) while the Fisher exact test will be used for the 
incidence of PCI values. 
The following SAS code will be used for CMH test:  
Proc Freq data=<dataset>; 
    Table CENTER*DRUG*OCCUR/CMH; 
Run; 
Where CENTER is the analysis center, DRUG is the randomized treatment group (EN3835 
1.68 mg total dose or placebo) and OCCUR is the incidence of the event variable.  
The following SAS code will be used for Wilcoxon rank sum test:  
Proc NPAR1WAY data=<dataset> Wilcoxon; 
    Class DRUG; 
    Var DEPVAR; 
Run; 
Where DRUG is the randomized treatment group (EN3835 1.68 mg total dose or placebo) and 
DEPVAR is the dependent variable.  

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The following SAS code will be used for the Fisher exact test:  
Proc Freq data=<dataset>; 
    Table DRUG*DEPVAR/Fisher; 
Run; 
Where DRUG is the randomized treatment group (EN3835 1.68 mg total dose or placebo) and 
OCCUR is the incidence of the event variable.  
The following SAS code will be used for ANCOVA with a factor of treatment group adjusted for 
baseline:  
Proc GLM data=<dataset>; 
    Class DRUG; 
    Model DEPVAR = DRUG CENTER BASE / ss3; 
Run; 
Where DRUG is the randomized treatment group (EN3835 1.68 mg total dose or placebo), 
CENTER is the analysis center, DEPVAR is the dependent variable, and BASE is the value of 
the dependent variable at baseline.  
The following SAS code will be used for ANOVA with a factor of treatment group:  
Proc GLM data=<dataset>; 
    Class DRUG; 
    Model DEPVAR = DRUG / ss3; 
Run; 
Where DRUG is the randomized treatment group (EN3835 1.68 mg total dose or placebo) and 
DEPVAR is the dependent variable.  
5.2. 
Analysis Centers 
Small centers will be combined into analysis centers for the CMH analyses. Any site with at least 
8 subjects per treatment arm will stand alone as an analysis center.  The smallest sites are to be 
pooled together until the analysis center has at least 8 subjects per treatment arm. The next larger 
centers will be then pooled together to reach at least 8 subjects per treatment arm, etc., until all 
analysis centers have at least 8 subjects per treatment arm. If the last pooled analysis center does 
not have at least 8 subjects per treatment arm, it will be pooled into the previously pooled center. 
If two or more small sites enrolled the same number of subjects in the study, the smaller number 
of subjects of either of the two treatment groups within a site or site ID number will be used to 
break the tie:  
• The site with the lowest number of subjects in either treatment group will be pooled 
first. 
• In the event the sites have the same lowest number of subjects in either treatment 
group, then the site with the lower site ID will be pooled first.  
Consistency of treatment response across analysis centers for the primary endpoint will be 
assessed by plotting the proportion of responders on the EN3835 arm versus the proportion of 
responders on the placebo arm by center. Additionally, site to site variability as well as analysis 
center to center variability will be assessed by the Breslow-Day test. 

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5.3. 
Missing Data Handling 
Missing efficacy data will be imputed or handled prior to each pre-specified statistical analysis 
by one of the following: 
• Missing data points are imputed as baseline values. For responder analysis, missing 
data are considered as non-responders 
• Last observation (post-dose) carried forward (LOCF) for the visit 
• Multiple imputation (MI) 
• Missing data points are not used in the analysis 
See individual sections for details. 
5.4. 
Subjects Given Incorrect Treatment 
All the efficacy analyses will be performed based on the randomized (ITT) treatment group 
regardless of actual treatments. All safety analyses will be based on actual treatment received by 
subjects and for overall summary any subjects who received EN3835 in at least 1 treatment 
session will be included in the EN3835 group and subjects who only received placebo during the 
study will be included in the placebo group. 
5.5. 
Subject Disposition 
The disposition summary will be summarized by treatment group and total (ie, 2 treatments 
combined) and will include: 
• Subjects screened 
• Subjects randomized/enrolled 
• Subjects in the ITT population 
• Subjects in the mITT population 
• Subjects in the safety population 
• Subjects in the PP population 
• Subjects who complete the study 
• Subjects who early terminated from the study 
• Subjects who early terminated from the study by termination reason 
• Time in the study 
• Subjects at each investigational site 

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5.6. 
Demographics and Baseline Characteristics 
Demographics and baseline characteristics will be summarized by treatment group and total and 
will include: 
• Age 
• Age category (<25, 25-34, 35-44, and 45 years of age or greater) 
• Gender 
• Race 
• Ethnicity 
• Weight (in kg) 
• Height (in cm) 
• BMI (in kg/m2) 
• BMI group (underweight [<18.5 kg/m2], normal weight [18.5-<25 kg/m2], overweight 
[25.0-<30 kg/m2], obese [≥30 kg/m2]) 
• Skin category based on Fitzpatrick scale rating 
• Alcohol use  
• Tobacco use  
5.7. 
EFP Risk Factors and EFP History 
EFP risk factors and EFP history characteristics variables will be summarized by treatment group 
and total and will include: 
• Family history of cellulite 
• Medical history of Dupuytren’s disease, knuckle pads, Ledderhose’s disease, 
diabetes, epilepsy (see section 3.7.2) 
• Age at EFP symptom onset (in years) 
• Prior treatments for EFP including liposuction, laser, massage, radiofrequency, 
surgery (subcision and powered subcision), drug, cryolipolysis, buttock implants,  
mesotherapy, cream, other, or none. Subjects can report more than 1 prior EFP 
treatment. 
• Number of prior EFP treatments (0, 1, 2, or ≥3) 
• Time since most recent EFP treatment (in years) 

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5.8. 
Cellulite Baseline Severity 
5.8.1. 
Cellulite Severity at Screening 
For each buttock (target or non-target), EFP severity at Screening will be summarized by 
treatment group and total and will include: 
• Subject PR-PCSS rating at Screening 
• Investigator CR-PCSS rating at Screening 
• PR-PCSS ratings versus CR-PCSS ratings at Screening 
5.8.2. 
Cellulite Baseline Severity 
For each buttock (target or non-target), EFP baseline severity will be summarized by treatment 
group and total and will include: 
• Subject PR-PCSS rating at Day 1 
• Investigator CR-PCSS rating at Day 1 
• PR-PCSS ratings versus CR-PCSS ratings at Day 1 
5.8.3. 
Cellulite Severity at Screening Versus Day 1 
For each buttock (target or non-target), cross tabulation of EFP severity at Screening versus at 
Day 1 will be summarized by treatment group and total and will include: 
• Subject PR-PCSS ratings 
• Investigator CR-PCSS ratings 
5.9. 
Efficacy Evaluation 
The integrated summary and statistical inference (p values and 95% confidence intervals) of the 
primary and key secondary endpoints based on two design-identical, double-blind, placebo-
controlled, phase 3 studies, EN3835-302 and EN3835-303, will be performed in the Integrated 
Summary of Efficacy (ISE) to provide more accurate and substantial evidence of efficacy of 
EN3835 in the treatment of EFP on the buttocks in adult women. 
5.9.1. 
Overview of Treatment 
The following information regarding treatment sessions for the target buttock will be 
summarized by treatment group: 
• Number of treatment sessions per subject 
• Number of subjects who had treatment done or treatment not done at each treatment 
visit 
• For subjects who had the treatment done, the number of subjects who got all 
12 injections in the target buttock at the treatment visit or who received less than 
12 injections in the target buttock and the reason why (see section 3.2) 

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• For subjects who did not have the treatment done, the reason why the treatment was 
not done (see section 3.2) 
• Number of injections given at each treatment visit 
• Number of dimples treated at each treatment visit  
• Number of injections per dimple at each treatment visit (calculated) 
The following information regarding treatment sessions for the non-target buttock will be 
summarized by treatment group: 
• Number of treatment sessions per subject 
• Number of subjects who had treatment done or treatment not done at each treatment 
visit 
• For subjects who had the treatment done, the number of subjects who got all 
12 injections in the non-target buttock at the treatment visit or who received less than 
12 injections in the non-target buttock and the reason why (see section 3.2) 
• For subjects who did not have the treatment done, the reason why the treatment was 
not done (see section 3.2) 
• Number of injections given at each treatment visit 
• Number of dimples treated at each treatment visit  
• Number of injections per dimple at each treatment visit (calculated) 
For the two buttocks overall, the following information regarding treatment sessions will be 
summarized by treatment group: 
• Number of treatment sessions given overall per subject 
• Total number of treatment sessions given overall 
• Number of injections given at each treatment visit 
• Number of dimples treated at each treatment visit  
• Number of injections per dimple at each treatment visit (calculated) 
Subjects who did not receive all 3 treatment sessions will be listed. The listing will include the 
treatment group, subject ID, treatment area, treatment not done, and the reason why no treatment 
was done. 
Subjects who did not receive 12 injections at a treatment visit for any treated buttock will be 
listed. The listing will include the treatment group, subject ID, treatment area, treatment visit, 
number of injections given, and the reason why 12 injections were not given. 
5.9.2. 
Multiple Comparisons for Efficacy Endpoints 
Individual p values obtained in section 5.9.3 through section 5.9.6 (also called raw p values) 
form a basis for multiple comparisons with type 1 error controlled for the study efficacy 
endpoints. The overall type 1 error rate is 0.05 for the study. A hierarchical gatekeeping 
procedure is used to control the family-wise error rate between families of efficacy endpoints 

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(primary and key secondary endpoints). Table 10 lists the multiplicity tests for efficacy 
endpoints. 
The multiple comparison results will be used for a claim of EN3835 treatment effect against 
placebo.  
Table 10: 
Multiplicity Tests for Efficacy Endpoints 
Order 
Group 
Endpoint 
Raw  
P Value a 
Significance 
at 0.05 b 
1 
Primary 
Two-level composite responders of the target 
buttock at Day 71 
x.xxx 
* 
2 
Secondary 
Family #1 
One-level PR-PCSS responders of the target 
buttock at Day 71 
x.xxx 
* 
2 
Secondary 
Family #1 
Two-level PR-PCSS responders of the target 
buttock at Day 71 
x.xxx 
* 
2 
Secondary 
Family #1 
One-level composite responders of the target 
buttock at Day 71 
x.xxx 
* 
2 
Secondary 
Family #1 
Two-level composite responders of the non-target 
buttock at Day 71 
x.xxx 
* 
3 
Secondary 
Family #2 
One-level SSRS responders at Day 71 
x.xxx 
* 
3 
Secondary 
Family #2 
Change from baseline (Day 1) of the PR-CIS total 
score at Day 71 
x.xxx 
 
4 
Secondary 
Family #3 
One-level S-GAIS responders of the target buttock 
at Day 71 
x.xxx 
 
4 
Secondary 
Family #3 
Two-level S-GAIS responders of the target buttock 
at Day 71 
x.xxx 
 
a P value from pre-defined analysis without multiplicity adjustment. 
b Asterisk (*) represents statistical significance at significant level of 0.05, see sections 5.9.3 - 5.9.6.  
PR-CIS=Patient Reported Cellulite Impact Scale; PR-PCSS=Patient Reported Photonumeric Cellulite Severity 
Scale; S-GAIS=Subject Global Aesthetic Improvement Scale; SSRS=Subject Self-rating Scale 
5.9.3. 
Primary Endpoint 
The rate of subjects who are 2-level composite responders (see section 3.5.8.3) for the target 
buttock will be summarized by treatment group with counts and percentages based on the 
ITT population. P value (raw p value for the multiplicity test) will be computed using CMH test 
adjusted for analysis center (see section 5.1). A cross-tabulation summary of subject 2-level 
responders versus investigator 2-level responders for the target buttock will be presented by 
treatment group.  
If the 2-level composite responder status of the target buttock cannot be determined at Day 71, 
ie, the target buttock is missing a CR-PCSS rating, a PR-PCSS rating, or both, then the subject 
will be classified as a non-responder of the target buttock.  
5.9.4. 
Key Secondary Endpoints – Family #1 
The 1-level PR-PCSS responders for the target buttock (see section 3.5.1.3), the 2-level 
PR-PCSS responders for the target buttock (see section 3.5.1.3), the 1-level composite 
responders for the target buttock (see section 3.5.8.1), and the 2-level composite responders for 
the non-target buttock (see section 3.5.8.2) at Day 71 will be summarized by treatment group 

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with counts and percentages based on the ITT population. Any missing value at Day 71 will be 
imputed as a non-responder in the analysis. P values (raw p values for the multiplicity test) will 
be computed using CMH test adjusted for analysis center (see section 5.1).  
The inference for each of 4 key secondary Family #1 endpoints is primarily based on the results 
at the Day 71 using the Bonferroni method if and only if the primary endpoint is claimed 
statistically significant (raw p value<0.05). 
5.9.5. 
Key Secondary Endpoints – Family #2 
The 1-level SSRS responders (see section 3.5.4.2) and the change from baseline in the PR-CIS 
total score (see section 3.5.3.9) at Day 71 will be summarized by treatment group with counts 
and percentages based on the ITT population. Any missing value at Day 71 will be imputed as a 
non-responder or a baseline value in the analysis. P values (raw p values for the multiplicity test) 
will be computed using CMH test adjusted for analysis center (see section 5.1).  
The inference for each of 2 key secondary Family #2 endpoints is conducted if and only if at 
least one of 4 key secondary endpoints in the first family is claimed statistically significant (raw 
p value<0.0125). Unused alpha (0.05, 0.0375, 0.025, 0.0125 corresponding to 4, 3, 2, or 1 of the 
key secondary endpoints in the first Family being statistically significant, respectively) from the 
Family #1 tests will be carried over to the inference of 2 key secondary endpoints in the second 
Family. The inference for each of 2 key secondary Family #2 endpoints will be based on the raw 
p value, unused alpha and the Bonferroni method for alpha spending.  
5.9.6. 
Key Secondary Endpoints – Family #3 
The 1-level S-GAIS responders for the target buttock and the 2-level S-GAIS responders for the 
target buttock (see section 3.5.2.2) at Day 71 will be summarized by treatment group with counts 
and percentages based on the ITT population. Any missing value at Day 71 will be imputed as a 
non-responder in the analysis. P values (raw p values for the multiplicity test) will be computed 
using CMH test adjusted for analysis center (see section 5.1).  
The inference for each of 2 key secondary Family #3 endpoints is conducted if and only if at 
least one of 2 key secondary endpoints in the second family is claimed statistically significant 
(raw p value<half of the unused alpha from the Family #1). Unused alpha from Family #2 tests, 
ie, half of unused alpha from the Family #1 tests multiplied by number of endpoints in the 
Family #2 that are deemed statistically significant from the multiple tests, will be carried over to 
the inference of 2 key secondary endpoints in the 3rd Family. The inference for each of 2 key 
secondary Family #3 endpoints will be based on the raw p value, unused alpha and the 
Bonferroni method for alpha spending.  
5.9.7. 
Sensitivity Analyses 
The following sensitivity analyses will be conducted for the primary efficacy endpoint. Selected 
sensitivity analyses will be conducted for key secondary efficacy endpoints, as indicated below. 
The ITT population will be used for sensitivity analyses unless otherwise noted. 

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5.9.7.1. 
Multiple Imputation (MI) for Missing Data 
Primary Endpoint: 2-level composite responders for the target buttock,   
Key Secondary endpoints: 1-level composite responders for the target buttock and 2-level 
composite responders for the non-target buttock 
A sensitivity analysis examining the potential impact of missing data on the result of the primary 
efficacy analysis will be performed using multiple imputation. The individual components 
(PR-PCSS and CR-PCSS) of the primary endpoint (two-level composite responders of the target 
buttock at Day 71) will be imputed separately on the original 5-point ordinal scales (rating 0-4) 
within each treatment group with missing values.  Multiple datasets (100 datasets) will be 
generated using the logistic regression method in SAS PROC MI. The logistic models for Day 71 
PR-PCSS and Day 71 CR-PCSS will include the ‘core’ variables, baseline value, and value at a 
previous visit. The core variables include age, baseline BMI, Fitzpatrick skin type (I-III versus 
IV-VI), and number of treatments received. A pre-specified seed will be used in SAS procedure 
PROC MI which is listed in Table 11. The imputed primary composite endpoint will be derived 
based on the imputed individual components (Day 71 PR-PCSS and Day 71 CR-PCSS). Each 
imputed dataset will be analyzed via the CMH test, adjusting for analysis center. The values of 
the general association test statistic from the CMH analysis will be transformed using the 
Wilson-Hilferty transformation (2) to create a more normally distributed statistic: 
9
2
9
7
CMH
3




−
=
z
 
The resulting transformed values will be pooled using PROC MIANALYZE in SAS to yield the 
corresponding pooled p value. 
Table 11: 
Initial Seeds for Multiple Imputations 
Order 
Variable 
Initial Seed 
1 
CR-PCSS rating score 
1315377 
2 
PR-PCSS rating score 
4586501 
3 
S-GAIS rating score 
6788473 
4 
SSRS rating score 
9346929 
5 
PR-CIS total score 
5194632 
CR-PCSS=Clinician Reported Photonumeric Cellulite Severity Scale; PR-PCSS=Patient Reported Photonumeric 
Cellulite Severity Scale; S-GAIS=Subject Global Aesthetic Improvement Scale; SSRS=Subject Self-rating Scale; 
PR-CIS=Patient Reported Cellulite Impact Scale 
Key Secondary Endpoints – Binary Responder Endpoints sections 5.9.4, 5.9.5, and 5.9.6:  
  1-level PR-PCSS responders for the target buttock,  
  2-level PR-PCSS responders for the target buttock,  
  1-level SSRS responders,  
  1-level S-GAIS responders for the target buttock and  
  2-level S-GAIS responders for the target buttock 
A similar approach that was used for composite binary responder sensitivity analysis will be used 
for this group of binary responder endpoints. Multiple imputation (MI) will be performed only 

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on the raw reported scales and then the responder variables will be derived based on the imputed 
raw reported scales.  
Key Secondary Endpoints – Continuous Endpoint section 5.9.5 
  Change from baseline in PR-CIS total score 
For this variable, the imputation will be performed on the endpoint directly by using the linear 
regression method in SAS PROC MI within each treatment group with missing data. The 
regression model will include the ‘core’ variables and corresponding baseline value. 
Once all the missing data are imputed, each set of imputed data will be analyzed and the 
resulting statistics from 100 sets will be combined using PROC MIANALYZE for the statistical 
inference from the ANCOVA with factor variables: treatment group and analysis center, and 
covariate variable: baseline PR-CIS total score. The resulting least square means (LSMEANs) 
and standard errors (SEs) of the LSMEANs will be pooled using PROC MIANALYZE to yield 
the corresponding p value. 
5.9.7.2. 
Tipping Point Analysis 
A sensitivity analysis examining the robustness of the results of the primary efficacy analysis to 
assumptions about missing data will be performed using a Tipping Point (TP) analysis. More 
specifically, the TP analysis will examine under what conditions the conclusion of the study 
remains unchanged, even if the missing data mechanism depends on the unobservable missing 
values and the data are Missing Not At Random (MNAR). 
In the TP analysis, missing values of the composite primary efficacy endpoint (2-point composite 
responder for target buttock at Day 71) will be assigned based on treatment group and analysis 
center.   
Define the following values based on the observed data: 
mp = the number of subjects in the placebo group with missing primary efficacy endpoint 
mt = the number of subjects in the EN3835 group with missing primary efficacy endpoint 
The basis of the TP analysis will be an mp -by- mt grid with mt values along the x-axis and mp 
values along the y-axis.  Each grid point (i,j) will contain a summary statistic sij corresponding to 
the result of the primary analysis with random responder assignment of missing data such that 
there are i additional responders in the EN3835 group and j additional responders in the placebo 
group.   
First, the data is analyzed under the “worst case” conditions.  In this step, all subjects in the 
placebo group with missing primary efficacy endpoint are assumed to be responders and all 
subjects in the EN3835 group are assumed to be non-responders. This is a distinct condition from 
that of the data from the main analysis in which all subjects with missing outcome are assumed 
to be non-responders, regardless of treatment group. The “worst case” dataset is analyzed using 
the same methodology as that for the primary endpoint defined in section 5.9.3 (ie, using CMH 
test adjusted for analysis center). If the result of the analysis of the “worst case” dataset supports 
the conclusion of the main study analysis (ie, both analyses provide statistically significant 
evidence for a positive treatment effect), then there is no need to implement the full TP analysis 
and the result of the main study analysis is robust to assumptions about the missing efficacy data.   

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If the analysis of the “worst case” dataset reverses the conclusion of the main study analysis, 
then the TP analysis will be performed by performing responder assignment based on treatment 
group and analysis center, and calculating summary statistics sij for additional grid points (i,j).  
Starting at the at grid location corresponding to the “worst case” condition (0, mp) an incremental 
step in both directions will be taken to grid location (1, mp -1).  For the responder assignment, 
the number of datasets Dijz will be generated, taking analysis center into account, depending on 
the number of patients with missing data at specific analysis centers.   
Each dataset Dijz is analyzed using the same methodology as that for the primary endpoint 
defined in section 5.9.3 (ie, using CMH test adjusted for analysis center). The results of the 
analysis over all Dijz are summarized using a pooled p value from the vij datasets, based on the 
method of Wilson-Hilferty transformation. The pooled p  value from this set of datasets will be 
the summary statistic sij for grid location (i,j). If at any point summary statistic sij is not less than 
the critical p value defined in section 5.9.3, and therefore reverses the conclusion of the primary 
analysis of the study, then that point represents one condition of the Tipping Point. 
The TP analysis will continue at grid locations (2, mp -2), (3, mp -3), etc., by repeating the 
process of random responder assignment, analyzing the data, then calculating the pooled p value 
until the first location of the Tipping Point is reached. Once one grid location of the Tipping 
Point is found, all eight adjacent grid locations will be searched to reveal additional Tipping 
Point grid locations. The process will be repeated until all Tipping Point grid locations are found. 
A summary table and a figure will be presented for the TP analysis which will display the 
collection of points identified as the Tipping Points. 
5.9.7.3. 
Missing Data Handled by a Last Observation (Post-dose) Carried Forward 
(LOCF) 
Missing data at Day 71 will be imputed as follows: 
• If the subject has at least one post-dose classification then the last classification will be 
carried forward for Day 71 for the analysis 
• If the subject has no post-dose classification then the baseline value will be carried 
forward for Day 71 for the analysis 
5.9.7.4. 
Other Sensitivity Analyses 
The primary efficacy endpoint and all the key secondary efficacy endpoints will be summarized 
by treatment group with descriptive statistics based on the PP population if the number of 
subjects in the PP population is 90% or less than those in the mITT population, ie, if more than 
10% of subjects are excluded in the PP population compared to those in the mITT population. 
P value will be computed using ANCOVA with factors of treatment group and analysis center 
adjusting for baseline value for change from baseline in the PR-CIS score or CMH test adjusted 
for analysis center for other efficacy endpoints (see section 5.1). In addition, similar summary 
and statistical analysis will be performed based on the observed data at Day 71, ie, using 
observed data without missing data imputed, for the mITT population as well as the 
PP population if more than 10% of subjects are excluded in the PP population compared to those 
in the mITT population. 

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5.9.8. 
Supportive Efficacy Endpoints 
All the supportive efficacy endpoints for the target buttock or the non-target buttock or 
two buttocks (see section 3.5) will be analyzed based on the mITT population at all the visits 
where missing values will not be imputed (observed data only). In addition, all the supportive 
efficacy endpoints with missing data handled using the LOCF approach will be performed at 
Day 71. If no classification post the initial treatment is available then the subject will be 
excluded in the analyses. 
Analysis summaries will be performed by either the target buttock, the non-target buttock, at 
least one buttock, or both buttocks in the same individual subject. 
If the number of subjects in the PP population is 90% or more than those in the mITT population, 
all the supportive efficacy endpoint analyses will also be analyzed based on the PP population. 
5.9.8.1. 
Endpoints Based on Subject PR-PCSS Rating 
The subject PR-PCSS ratings for the target buttock will be summarized by treatment group at 
baseline (Day 1), Day 22, Day 43, Day 71, and Day 71 (LOCF) with counts and percentages at 
each severity rating and with means and standard deviations, respectively.  
The subject PR-PCSS ratings for the non-target buttock will be summarized by treatment group 
at baseline (Day 1), Day 22, Day 43, Day 71, and Day 71 (LOCF) with counts and percentages at 
each severity rating and with means and standard deviations, respectively. 
The change from baseline rating of PR-PCSS rating for the target buttock will be summarized by 
treatment group at Day 22, Day 43, Day 71, and Day 71 (LOCF) with counts at each rating 
change and with means and standard deviations, respectively. The change from baseline rating 
can vary from -4 (change from severe [rating = 4] to none [0]) to +1 (change from moderate [3] 
to severe [4]). P values will be computed for change from baseline rating at each visit with 
Wilcoxon rank sum test. 
The change from baseline rating of PR-PCSS rating for the non-target buttock will be 
summarized by treatment group at Day 22, Day 43, Day 71, and Day 71 (LOCF) with counts at 
each rating change and with means and standard deviations, respectively. The change from 
baseline rating can vary from -4 (change from severe [rating = 4] to none [0]) to +1 (change from 
moderate [3] to severe [4]). P values will be computed for change from baseline rating at each 
visit with Wilcoxon rank sum test. 
The subject 2-level PR-PCSS responder and 1-level PR-PCSS responder for the target buttock 
will be summarized by treatment group at Day 22, Day 43, Day 71, and Day 71 (LOCF) with 
counts and percentages, respectively. P values will be computed at each visit using a CMH test 
adjusted for analysis center. 
The subject 2-level PR-PCSS responder and 1-level PR-PCSS responder for the non-target 
buttock will be summarized by treatment group at Day 22, Day 43, Day 71, and Day 71 (LOCF) 
with counts and percentages, respectively. P values will be computed at each visit using a CMH 
test adjusted for analysis center. 

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The subject 2-level PR-PCSS responder and 1-level PR-PCSS responders for at least one buttock 
will be summarized by treatment group at Day 22, Day 43, Day 71, and Day 71 (LOCF) with 
counts and percentages, respectively. P values will be computed at each visit using a CMH test 
adjusted for analysis center. 
The subject 2-level PR-PCSS responder and 1-level PR-PCSS responders for the two buttocks in 
the same individual subject will be summarized by treatment group at Day 22, Day 43, Day 71, 
and Day 71 (LOCF) with counts and percentages, respectively. P values will be computed at 
each visit using a CMH test adjusted for analysis center. 
5.9.8.2. 
Endpoints Based on Subject S-GAIS Rating 
The subject S-GAIS ratings (-3 to +3) for the target buttock will be summarized by treatment 
group at Day 22, Day 43, Day 71, and Day 71 (LOCF) with counts and percentages at each 
rating and with means and standard deviations, respectively. P values will be computed for 
change from baseline ratings at each visit with Wilcoxon rank sum test. 
The subject S-GAIS ratings (-3 to +3) for the non-target buttock will be summarized by 
treatment group at Day 22, Day 43, Day 71, and Day 71 (LOCF) with counts and percentages at 
each rating and with means and standard deviations, respectively. P values will be computed for 
change from baseline ratings at each visit with Wilcoxon rank sum test. 
The subject 1-level S-GAIS responder for the target buttock will be summarized by treatment 
group at Day 22, Day 43, Day 71, and Day 71 (LOCF) with counts and percentages, 
respectively. P values will be computed at each visit using a CMH test adjusted for analysis 
center. 
The subject 1-level S-GAIS responder for the non-target buttock will be summarized by 
treatment group at Day 22, Day 43, Day 71, and Day 71 (LOCF) with counts and percentages, 
respectively. P values will be computed at each visit using a CMH test adjusted for analysis 
center. 
The subject 1-level S-GAIS responder for at least one buttock will be summarized by treatment 
group at Day 22, Day 43, Day 71, and Day 71 (LOCF) with counts and percentages, 
respectively. P values will be computed at each visit using a CMH test adjusted for analysis 
center. 
The subject 1-level S-GAIS responders for the two buttocks in the same individual subject will 
be summarized by treatment group at Day 22, Day 43, Day 71, and Day 71 (LOCF) with counts 
and percentages, respectively. P values will be computed at each visit using a CMH test adjusted 
for analysis center. 
5.9.8.3. 
Endpoints Based on Subject PR-CIS Ratings 
The subject PR-CIS score of each individual item, total score or abbreviated total score will be 
summarized by treatment group at baseline (Day 1), Day 71 and Day 71 (LOCF) with n, mean, 
SD, median, minimum and maximum.  

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The change from baseline in subject PR-CIS score of each individual item, total score or 
abbreviated total score will be summarized by treatment group at Day 71 and Day 71 (LOCF) 
with n, mean, SD, median, minimum and maximum. P values will be computed for change from 
baseline in subject PR-CIS score of each individual item, total score or abbreviated total score at 
Day 71 and Day 71 (LOCF) with ANCOVA with factors of treatment group and analysis center 
adjusted for baseline values. 
The subject PR-CIS responder for each individual item will be summarized by treatment group at 
Day 71 and Day 71 (LOCF) with counts and percentages, respectively. P values will be 
computed at each visit using a CMH test adjusted for analysis center. 
The subject PR-CIS responder for total score will be summarized by treatment group at Day 71 
and Day 71 (LOCF) with counts and percentages, respectively. P values will be computed at 
each visit using a CMH test adjusted for analysis center. 
The subject PR-CIS responder for abbreviated total score will be summarized by treatment group 
at Day 71 and Day 71 (LOCF) with counts and percentages, respectively. P values will be 
computed at each visit using a CMH test adjusted for analysis center. 
5.9.8.4. 
Endpoints Based on SSRS Ratings 
The subject SSRS ratings (0 to 6) will be summarized by treatment group at Baseline, Day 71 
and Day 71 (LOCF), ie, Day 71/Early Termination, with counts and percentages at each rating 
and with means and standard deviations. P values will be computed using Wilcoxon rank sum 
test.  
The subject 1-level SSRS responders will be summarized by treatment group at Day 71, and 
Day 71 (LOCF) with counts and percentages, respectively. P values will be computed using a 
CMH test adjusted for analysis center. 
5.9.8.5. 
Endpoints Based on Subject Satisfaction With Cellulite Treatment 
The subject satisfaction ratings with cellulite treatment (-2 to +2) will be summarized by 
treatment group at Day 71 and Day 71 (LOCF), ie, Day 71/Early Termination, with counts and 
percentages at each rating and with means and standard deviations. P values will be computed 
using Wilcoxon rank sum test.  
The subject satisfied responders will be summarized by treatment group at Day 71, and Day 71 
(LOCF) with counts and percentages, respectively. P values will be computed using a CMH test 
adjusted for analysis center. 
5.9.8.6. 
Endpoints Based on Investigator CR-PCSS Rating 
The investigator CR-PCSS ratings for the target buttock will be summarized by treatment group 
at baseline (Day 1), Day 22, Day 43, Day 71, and Day 71 (LOCF) with counts and percentages at 
each severity rating and with means and standard deviations, respectively.  
The investigator CR-PCSS ratings for the non-target buttock will be summarized by treatment 
group at baseline (Day 1), Day 22, Day 43, Day 71, and Day 71 (LOCF) with counts and 
percentages at each severity rating and with means and standard deviations, respectively.  

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The change from baseline investigator CR-PCSS rating for the target buttock will be summarized 
by treatment group at Day 22, Day 43, Day 71, and Day 71 (LOCF) with counts at each rating 
change and with means and standard deviations, respectively. The change from baseline rating 
can vary from -4 (change from severe to none) to +1 (change from moderate to severe). P values 
will be computed for change from baseline ratings at each visit with Wilcoxon rank sum test. 
The change from baseline investigator CR-PCSS rating for the non-target buttock will be 
summarized by treatment group at Day 22, Day 43, Day 71, and Day 71 (LOCF) with counts at 
each rating change and with means and standard deviations, respectively. The change from 
baseline rating can vary from -4 (change from severe to none) to +1 (change from moderate to 
severe). P values will be computed for change from baseline ratings at each visit with Wilcoxon 
rank sum test. 
The investigator 2-level CR-PCSS responder and 1-level CR-PCSS responder for the target 
buttock will be summarized by treatment group at Day 22, Day 43, Day 71, and Day 71 (LOCF) 
with counts and percentages, respectively. P values will be computed at each visit using a CMH 
test adjusted for analysis center. 
The investigator 2-level CR-PCSS responder and 1-level CR-PCSS responder for the non-target 
buttock will be summarized by treatment group at Day 22, Day 43, Day 71, and Day 71 (LOCF) 
with counts and percentages, respectively. P values will be computed at each visit using a CMH 
test adjusted for analysis center. 
The investigator 2-level CR-PCSS responder and 1-level CR-PCSS responders for at least one 
buttock will be summarized by treatment group at Day 22, Day 43, Day 71, and Day 71 (LOCF) 
with counts and percentages, respectively. P values will be computed at each visit using a CMH 
test adjusted for analysis center. 
The investigator 2-level CR-PCSS responder and 1-level CR-PCSS responders for the two 
buttocks in the same individual subject will be summarized by treatment group at Day 22, 
Day 43, Day 71, and Day 71 (LOCF) with counts and percentages, respectively. P values will be 
computed at each visit using a CMH test adjusted for analysis center. 
5.9.8.7. 
Endpoints Based on Investigator I-GAIS Rating 
The investigator I-GAIS ratings (-3 to +3) for the target buttock will be summarized by treatment 
group at Day 22, Day 43, Day 71, and Day 71 (LOCF) with counts and percentages at each 
rating and with means and standard deviations, respectively. P values will be computed for 
change from baseline ratings at each visit with Wilcoxon rank sum test. 
The investigator I-GAIS ratings (-3 to +3) for the non-target buttock will be summarized by 
treatment group at Day 22, Day 43, Day 71, and Day 71 (LOCF) with counts and percentages at 
each rating and with means and standard deviations, respectively. P values will be computed for 
change from baseline ratings at each visit with Wilcoxon rank sum test. 
The investigator 1-level I-GAIS responder for the target buttock will be summarized by 
treatment group at Day 22, Day 43, Day 71, and Day 71 (LOCF) with counts and percentages, 
respectively. P values will be computed at each visit using a CMH test adjusted for analysis 
center. 

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The investigator 1-level I-GAIS responder for the non-target buttock will be summarized by 
treatment group at Day 22, Day 43, Day 71, and Day 71 (LOCF) with counts and percentages, 
respectively. P values will be computed at each visit using a CMH test adjusted for analysis 
center. 
The investigator 1-level I-GAIS responder for at least one buttock will be summarized by 
treatment group at Day 22, Day 43, Day 71, and Day 71 (LOCF) with counts and percentages, 
respectively. P values will be computed at each visit using a CMH test adjusted for analysis 
center. 
The investigator 1-level I-GAIS responder for the two buttocks in the same individual subject 
will be summarized by treatment group at Day 22, Day 43, Day 71, and Day 71 (LOCF) with 
counts and percentages, respectively. P values will be computed at each visit using a CMH test 
adjusted for analysis center. 
5.9.8.8. 
Endpoints Based on Subject PR-PCSS Rating and Investigator CR-PCSS Rating 
The subject/investigator 2-level composite responder and 1-level composite responder for the 
target buttock will be summarized by treatment group at Day 22, Day 43, Day 71, and Day 71 
(LOCF) with counts and percentages, respectively. P values will be computed at each visit using 
a CMH test adjusted for analysis center. 
The subject/investigator 2-level composite responder and 1-level composite responder for the 
non-target buttock will be summarized by treatment group at Day 22, Day 43, Day 71, and 
Day 71 (LOCF) with counts and percentages, respectively. P values will be computed at each 
visit using a CMH test adjusted for analysis center. 
The subject/investigator 2-level composite responder and 1-level composite responder for at least 
one buttock will be summarized by treatment group at Day 22, Day 43, Day 71, and Day 71 
(LOCF) with counts and percentages, respectively. P values will be computed at each visit using 
a CMH test adjusted for analysis center. 
The subject/investigator 2-level composite responder and 1-level composite responder for the 
two buttocks in the same individual subject will be summarized by treatment group at Day 22, 
Day 43, Day 71, and Day 71 (LOCF) with counts and percentages, respectively. P values will be 
computed at each visit using a CMH test adjusted for analysis center. 
5.9.8.9. 
Change from Baseline in PR-PCSS by S-GAIS Rating at Day 71 
The change from baseline (or severity improvement) in PR-PCSS at Day 71 will be summarized 
by S-GAIS rating grouped by: 
• Treatment group and buttock 
• Treatment group and two buttocks combined 
• Buttock and two treatments combined 
• Overall 

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5.9.8.10. By-center Exploratory Analyses 
By-center summaries will be based on the mITT population.  
The following treatment related variables will be summarized by analysis center and treatment 
group and by each of the two buttocks: 
• Percentage of subjects given full treatment exposure for that buttock (12 injections) at 
each treatment session 
• Average number of injections given, average numbers of dimples treatment, and 
average number of injections per dimple 
The following efficacy variables will be summarized by analysis center and treatment group: 
• Subject PR-PCSS rating at baseline, Day 71 (LOCF), and change from baseline for 
the target buttock 
• Subject PR-PCSS rating at baseline, Day 71 (LOCF), and change from baseline for 
the non-target buttock 
• Subject PR-PCSS responder analysis of 2-level responders and 1-level responders at 
Day 71 (LOCF) for the target buttock 
• Subject PR-PCSS responder analysis of 2-level responders and 1--level responders at 
Day 71 (LOCF) for the non-target buttock 
• Subject PR-PCSS responder analysis of 2-level responders and 1-level responders at 
Day 71 (LOCF) for at least one buttock 
• Subject PR-PCSS responder analysis of 2-level responders and 1-level responders at 
Day 71 (LOCF) for the two buttocks in the same individual subject 
• Investigator CR-PCSS rating at baseline, Day 71 (LOCF), and change from baseline 
for the target buttock 
• Investigator CR-PCSS rating at baseline, Day 71 (LOCF), and change from baseline 
for the non-target buttock 
• Investigator CR-PCSS responder analysis of 2-level responders and 1-level 
responders at Day 71 (LOCF) for the target buttock 
• Investigator CR-PCSS responder analysis of 2-level responders and 1-level 
responders at Day 71 (LOCF) for the non-target buttock 
• Investigator CR-PCSS responder analysis of 2-level responders and 1-level 
responders at Day 71 (LOCF) for at least one buttock 
• Investigator CR-PCSS responder analysis of 2-level responders and 1-level 
responders at Day 71 (LOCF) for the two buttocks in the same individual subject 
• Two-level composite responder and 1-level composite responder at Day 71 (LOCF) 
for the target buttock 
• Two-level composite responder and 1-level composite responder at Day 71 (LOCF) 
for the non-target buttock 

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• Two-level composite responder and 1-level composite responder at Day 71 (LOCF) 
for at least one buttock 
• Two-level composite responder and 1-level composite responder at Day 71 (LOCF) 
for the two buttocks in the same individual subject 
• Subject 1-level S-GAIS responders at Day 71 (LOCF) for the target buttock 
• Subject 1-level S-GAIS responders at Day 71 (LOCF) for the non-target buttock 
• Subject 1-level S-GAIS responders at Day 71 (LOCF) for at least one buttock 
• Subject 1-level S-GAIS responders at Day 71 (LOCF) for the two buttocks in the 
same individual subject 
• Investigator 1-level I-GAIS responders at Day 71 (LOCF) for the target buttock 
• Investigator 1-level I-GAIS responders at Day 71 (LOCF) for the non-target buttock 
• Investigator 1-level I-GAIS responders at Day 71 (LOCF) for at least one buttock 
• Investigator 1-level I-GAIS responders at Day 71 (LOCF) for the two buttocks in the 
same individual subject 
• PR-CIS total score at baseline, Day 71 (LOCF), and change from baseline 
• PR-CIS abbreviated total score at baseline, Day 71 (LOCF), and change from 
baseline 
• SSRS rating score at baseline and Day 71 (LOCF) 
• One-level SSRS Responders at Day 71 (LOCF) 
• Mean subject global satisfaction with cellulite treatment and percentage of subjects 
with ratings of satisfied and very satisfied 
5.10. 
Safety Evaluation 
5.10.1. 
Adverse Events 
The following listings will be provided based on all AEs: 
• Listing of deaths 
• Listing of non-fatal SAEs 
• Listing of non-serious AEs leading to discontinuation from study 
• Listing of non-serious AEs leading to interruption or discontinuation of study drug 
The following summary tables of AEs will be presented by treatment group: 
• TEAEs 
− Overall summary 
− By preferred term (overall, ≥5% and ≥2%, respectively)  
− By preferred term and severity 

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− By frequency of SAEs 
− By frequency of most common non-SAE 
• Treatment-related AEs  
− Overall summary 
− By preferred term (overall, ≥5% and ≥2%, respectively) 
− By preferred term and severity 
− By preferred term and treatment session 
− Duration of AEs 
• AEs of special interest 
− By preferred term  
The overall summary will consist of the following items:  
• Total number of AEs 
− All AEs 
− Mild AEs 
− Moderate AEs 
− Severe AEs 
• Total number of subjects with 
− At least 1 AE 
− At least 1 SAE  
− At least 1 severe AE  
− No severe AEs but at least 1 moderate AE 
− No severe/moderate AEs but at least 1 mild AE 
− At least 1 AE leading to discontinuation from study 
− At least 1 AE leading to interruption or discontinuation of study drug 
• Total number of subjects who died (treatment-emergent only) 
Percentages for the total number of mild, moderate, and severe AEs will be based on the total 
number of all AEs in the treatment group. 
The by frequency summaries will also include the total number of occurrences the AE preferred 
term was reported as well the number of subjects with at least 1 report of the AE. Most common 
non-SAEs are any preferred term AE that at least 5% of the subjects in 1 treatment group report 
at least once. Adverse events that are classified as most common in at least 1 treatment group 
will be reported in all treatment groups. 

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5.10.1.1. Adverse Event Conventions 
The following conventions will be followed: 
• Table by preferred term - If an AE preferred term occurred multiple times within a 
body system for the same subject, the preferred term will only be counted once for the 
subject for the summary of preferred terms. If an AE body system occurred multiple 
times for the same subject, the body system will only be counted once for the subject 
for the summary of body systems. If a subject has any AE, the subject will be counted 
once in the summary of subjects with at least 1 AE. 
• Table by preferred term and severity - If an AE preferred term occurred multiple 
times within a body system for the same subject, only the most severe one will be 
used. If the most severe preferred term of an AE occurred multiple times within a 
body system for the same subject, only 1 will be counted. In addition, this summary 
will also contain the total number of subjects with at least 1 mild, 1 moderate, or 
1 severe. If a subject has at least 1 severe AE, then the subject will be counted in the 
severe category. If the subject has no severe AEs, but at least 1 moderate AE, then the 
subject will be counted in the moderate category, and if the subject has no severe and 
no moderate AEs, but has at least 1 mild AE, then the subject will be counted in the 
mild category. 
• Table by preferred term and treatment session – If an AE preferred term occurred 
multiple times within a body system for the same subject within a treatment session, 
the preferred term will only be counted once for the subject in the treatment session 
for the summary of preferred terms. If an AE preferred term occurred multiple times 
within a body system for the same subject in different treatment sessions, the 
preferred term will be counted at each treatment session. If an AE body system 
occurred multiple times for the same subject within a treatment session, the body 
system will only be counted once for the subject in the treatment session for the 
summary of body systems. If an AE body system occurred multiple times for the 
same subject in different treatment sessions, the body system will be counted at each 
treatment session for the summary of body systems. If a subject has any AE within a 
treatment session, the subject will be counted once in the treatment session in the 
summary of subjects with at least 1 AE. If a subject has any AE in different treatment 
sessions, the subject will be counted in each treatment session in the summary of 
subjects with at least 1 AE. 
• Table of treatment-related AEs by duration category – This summary will be based on 
individual events rather than subjects. Each related AE will be classified into one of 
duration categories (1-4 days, 5-7 days, 8-14 days, 14-21 days, or >21 days) based on 
its duration. If an AE preferred term occurred within a body system multiple times for 
the same subject, each occurrence will be counted in the summary. In addition, all 
related AEs by treatment will also be included in this summary. If the AE is reported 
as ongoing or the AE stop date is missing or incomplete, the AE duration will not be 
computed and the AE will not be included in the duration analysis. 

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• Table of frequency of preferred terms – Preferred terms will be ordered by their 
descending frequency within the EN3835 treatment group. If 2 or more preferred 
terms are tied in their frequency, then the preferred terms will be ordered 
alphabetically. 
5.10.2. 
Weight and BMI 
Weight and BMI at baseline, visit (Day 22, Day 43, and Day 71) and change from baseline will 
be summarized by treatment group.  
5.10.3. 
Vital Signs 
Vital signs at baseline (Day 1 pre-injection), all study visits (Day 22 pre-injection, Day 43 
pre-injection, and Day 71) and change from baseline (study baseline) will be summarized by 
treatment group. P values for change from baseline will be based on the ANOVA with a factor of 
treatment group. 
Vital signs on injection day will be summarized at baseline (pre-injection), all post-injection time 
points (15 minutes and 30 minutes) and change from baseline by treatment group. The baseline 
value will be based on the pre-injection measurement at each treatment session. 
The incidence of subjects with sponsor-defined PCI vital sign values (see Table 9) at any time 
during the study (including post-30-minute measurements) will be presented by treatment group. 
P values for the incidence of subjects with sponsor-defined PCI vital sign values will be based on 
the Fisher exact test. 
Any subject with at least 1 PCI vital sign will have all vital sign values listed. 
5.10.4. 
Clinical Laboratory 
Clinical laboratory results (hematology and chemistry only) at baseline, Day 71, and change 
from baseline will be summarized by treatment group. Routine urinalysis results will not be 
summarized. Any hematology or chemistry lab result not reported as a continuous value will not 
be included in the summaries. P values for change at Day 71 from baseline will be based on the 
ANOVA with a factor of treatment group. 
All post-injection laboratory values (Day 71 and unscheduled labs taken on Day 1 or later) will 
be used to determine the incidence of PCI laboratory values. The incidence of subjects with 
sponsor-defined PCI laboratory values (see Table 8) will be presented. P values for the incidence 
of subjects with sponsor-defined PCI laboratory values will be based on the Fisher exact test. 
Any subject with at least 1 PCI laboratory value will have all the values for that analyte listed. 
5.10.5. 
Immunogenicity 
Anti-AUX-I and anti-AUX-II antibody titer levels will be analyzed at Day 1, Day 22, Day 43, 
and Day 71 by treatment group. The immunogenicity analysis will summarize the number of 
subjects with an immunogenicity sample tested, the percent of subjects with a positive sample, 
and the average titer level of the positive samples. The titer levels will be log 10 transformed 
prior to being summarized. 

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The Day 71 LOCF anti-AUX-I and anti-AUX-II antibody titer levels will be summarized by 
treatment session cohorts (subjects with 1, 2, or 3 treatment cycles) and treatment group. 
The number and percentage of assayed serum samples that will detect the presence or absence of 
neutralizing antibodies (positive/negative) to AUX-I and AUX-II will be summarized by anti-
drug antibody quartiles for the EN3835-treated subjects with descriptive statistics (number and 
percentage) at Day 1 and Day 71. 
5.10.6. 
Concomitant Medications 
Concomitant medications will be summarized for preferred term (generic name from WHO 
dictionary) by treatment group. If 2 medications are coded to the same preferred term, it will be 
counted only once for a subject. Medications will be ordered alphabetically by drug class and 
preferred term within drug class.  
6. 
DERIVED VARIABLES 
6.1. 
Subject Level Variables 
The following variables will be determined for each subject (see Table 12). 
Table 12: 
Subject Level Derived Dataset Variables 
Variable 
Definition 
Age Group 
<35 years 
35 – <45 years 
45 – <65 years 
≥65 years 
Height (cm) 
If height unit is inches, then height is equal to the recorded value multiplied 
by 2.54 and then rounded to 1 decimal point. 
Weight (kg) 
If weight unit is pounds, then weight is equal to the recorded value multiplied 
by 0.454 and then rounded to 1 decimal point. 
BMI (kg/m2) 
Weight/(Height/100)2 
BMI Group 
Underweight (<18.5 kg/m2) 
Normal Weight (18.5 – <25.0 kg/m2) 
Overweight (25.0 – <30.0 kg/m2) 
Obese (≥30.0 kg/m2) 
Date of First Injection 
Day 1 visit date 
Last Date in Study 
Date of last visit where subject was seen by the investigator. 
If subject was lost to follow-up, then last date of contact. If the subject had 
contact with the site after the final visit (eg, to follow-up on an AE), the last 
visit date will still be used as last date in the study. 
Time in Study 
Last Date in Study – Date of First Injection + 1 
Age at EFP Symptom Onset 
Start Date of EFP Symptom Onset (from medical history) – Date of 
Birth/365.25, truncated to integer value. See section 6.2.2 for handling of 
partial or unknown EFP symptom onset dates. 
AE=Adverse event; BMI=Body mass index; EFP=Edematous fibrosclerotic panniculopathy 

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6.2. 
Safety Variables 
6.2.1. 
Adverse Events 
Adverse events will be organized in 2 different ways: by event and by subject. The by event 
dataset will include all the characteristics of the event obtained on the eCRF plus the derived 
variables presented in Table 13. A second by event dataset will be created for the AE duration 
analysis. This duration dataset will contain only the subject number, treatment session, body 
system classification, preferred term, and duration. 
Table 13: 
Adverse Event Variables by Event 
Variable 
Values/Definition 
Treatment-Emergent 
AE with a start date after the first dose of study medication 
Treatment-Related 
If relationship to study medication is reported as possible, probable or missing; ‘unlikely 
related’ AE will be classified as not a treatment-related AE. 
Onset Day 
AE Start Date - Date of First Injection + 1 
Duration 
AE Stop Date - AE Start Date + 1 
Treatment Session 
The number of the treatment session immediately preceding the AE onset date 
AE=Adverse event 
The by-subject dataset will summarize all the AE events for a subject and will include the 
variables presented in Table 14. The same variables will be computed for TEAEs and treatment-
related AEs. 
Table 14: 
Adverse Event Variables by Subject 
Variable 
Values/Definition 
Total AEs 
Sum of number of AEs the subject reported 
Total Mild AEs 
Sum of number of mild AEs the subject reported 
Total Moderate AEs 
Sum of number of moderate AEs the subject reported 
Total Severe AEs 
Sum of number of severe AEs the subject reported 
Had AE 
Flag (Y/N) to indicate subject had at least 1 AE 
Had Severe AE 
Flag (Y/N) to indicate subject had at least 1 AE of moderate or severe severity 
Had SAE 
Flag (Y/N) to indicate subject had at least 1 serious AE 
Had AE Leading to 
Discontinuation 
Flag (Y/N) to indicate subject had at least 1 AE that lead to discontinuation from the study 
AE=Adverse event; SAE=Serious adverse event; Y/N=Yes/No 
6.2.2. 
Laboratory Variables 
Laboratory variable, Creatinine clearance (eCrCl), will be derived by Endo using the 
Cockcroft-Gault formula (3) as follows: 
eCrCl (mL/min) = {[(140-age) × weight]/[72 × Scr]} × 0.85 for female, 
where age is expressed in years (y), weight is expressed in kilograms (kg), and serum creatinine 
concentration (Scr) is expressed in milligrams per deciliter (mg/dL). 

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6.3. 
Imputation of Partial Dates 
Study visit dates, birthdates, informed consent date, injection dates/times, all assessment dates, 
all lab dates, and date of completion/last contact date must be complete dates; no imputations 
will be done. No imputations will be done for partial medical history onset/resolution dates 
(except EFP onset date), partial alcohol/tobacco stop dates, partial AEs onset/end dates and 
partial concomitant medication/procedure start/stop dates. All AEs with a missing onset day will 
be considered treatment-emergent except if the onset month/year is prior to the first injection 
date. All medications/procedures with a missing onset and stop day will be considered 
concomitant except if the stop month/year is prior to the first injection date.  
For EFP onset date and prior EFP medications/treatment dates, missing onset days will be 
imputed with the first day of the month and missing onset month will be imputed with January. If 
the EFP onset date is indicated as completely unknown but starting less than 5 years ago, the 
EFP onset date will be imputed as the informed consent date minus 5 years. If the EFP onset date 
is indicated as completely unknown but starting more than 5 years ago, the EFP onset date will 
not be imputed. Missing EFP medication/treatment end days will be imputed with the last day of 
the month and missing end months will be imputed with December, except if the end year is 
equal to the date of injection year and then the EFP medication/treatment end date will be 
imputed with the first injection date. 
6.4. 
Relative Study Day/Treatment Session Study Day 
Relative study day will be computed for each visit and for each AE. For visits or events 
occurring on or after the Day 1 visit, relative study day will be the date of visit (event) minus the 
date of first injection + 1. For visits or events that occur prior to the Day 1 visit, the relative study 
day will be the date of visit (event) minus the date of first injection.  
Adverse events will have a treatment session study day, computed as the date of event minus the 
date of preceding injection + 1. 
6.5. 
Conventions and Algorithms 
6.5.1. 
Summary Tables/Subject Listings Conventions 
Summary tables, subject listings, graphs and any supportive SAS output will include a “footer” 
of explanatory notes that will indicate, when applicable:  
• Date of data extraction  
• Date and time of output generation 
• SAS program name, including the path, that generates the output 
Null summary tables will be presented with a note stating that “No Subjects Met Criteria.”  
The summary tables will clearly indicate the effective sample size per treatment group. All 
summary tables involving percentages will round the percentages off to 1 decimal place. All 
summary tables involving descriptive statistics of continuous variables will round the mean and 
median to 1 decimal place more than the variable’s standard form and round the standard 

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Table 15: 
Previous Results as Bases for Sample Size 
Efficacy Endpoint 
EN3835 
Placebo 
Power 
1-level PR-PCSS responders of the target buttock 
 
 
 
2-level PR-PCSS responders of the target buttock 
 
 
 
1-level composite responders of the target buttock 
 
 
 
2-level composite responders of the non-target buttock 
 
 
 
Proportion of subjects with SSRS rating ≥4 
 
 
 
Change in PR-CIS Score (Mean (SD)  
 
 
 
1-level S-GAIS responders of the target buttock 
 
 
 
 
2-level S-GAIS responders of the target buttock 
 
 
 
* Rates are estimated based on the reported results from the pooled pivotal studies of a drug approved for an 
aesthetic indication. 
PR-CIS=Patient Reported Cellulite Impact Scale; PR-PCSS=Patient Reported Photonumeric Cellulite Severity 
Scale; SD=Standard deviation; S-GAIS=Subject Global Aesthetic Improvement Scale; SSRS=Subject Self-rating 
Scale 
9. 
TABLES, LISTINGS, AND GRAPH SHELLS 
The layouts of the summary tables, subject listings, and graphs are presented in SAP Module 2. 
These layouts incorporate all the appropriate table titles, table numbers, and footnotes.  
10. 
CHANGE FROM PROTOCOL 
Table 16 lists any significant changes in the SAP from what is proposed in the protocol. 
Table 16: 
Changes from Protocol 
Text in Protocol 
Change in SAP 
Justification 
 
 
 

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11. 
REVISION HISTORY 
Non-editorial changes made to any of the sections of this SAP will be recorded in Table 17. All 
significant changes require a new signature page be completed. 
Table 17: 
Revision History 
Description of Change/Reason for Change 
Document 
Version Number 
Before Change 
Date of Change 
Original 
N/A 
N/A 
Section 4.4, Per-protocol (PP) population: Modified the exclusion 
criteria from the mITT population to the per-protocol population so 
that the per-protocol population is unambiguously defined 
1 
05-Jun-2018 
Section 5.2, Analysis Center: Modified the pooling procedure so that 
the analysis centers are uniquely formed. In addition, add the Breslow-
Day test to assess site to site variability and analysis center to center 
variability. 
1 
05-Jun-2018 
Section 5.9.7, Sensitivity Analyses: Added tipping point analysis for 
the primary and key secondary endpoints 
1 
05-Jun-2018 
Section 6.1, Subject Level Variables: modified the definition of age 
groups in Table 12 
1 
05-Jun-2018 
Section 5.9.7.1, Multiple Imputation (MI) for Missing Data: Re-
organize primary endpoint and key secondary endpoints into different 
groups in which how multiple imputations for missing data are 
implemented.  
2 
20-Aug-2018 
Section 5.9.7.2, Tipping Point Analysis: Original tipping point 
paragraph in Section 5.9.7.1 is extended to a new section. More 
detailed methodology and implementation as well terminology are 
given in the section. 
2 
20-Aug-2018 
Section 5.9, Efficacy Evaluation: Pre-specified analyses of the primary 
and key secondary endpoints have been added based on integrated data 
from two design-identical, double-blind, placebo-controlled, phase 3 
studies, EN3835-302 and EN3835-303. 
2.1 
30-Aug-2018 
N/A=Not applicable 

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12. 
REFERENCES 
1. US Food and Drug Administration. Guidance for Industry, E9 Statistical Principles for 
Clinical Studies (ICH E9); 1998:30. 
2. Wilson EB, Hilferty MM. The Distribution of Chi-Square. Proc Natl Acad Sci U S A. 
1931. 17(12):684-8. 
3. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. 
Nephron. 1976; 16(1):31-41.