A Phase 3b, Open-Label, Long-Term Study to Evaluate the Safety and Temporal Pattern of Response of EN3835 in the Treatment of Edematous Fibrosclerotic Panniculopathy
Phase: PHASE3
Conditions: Edematous Fibrosclerotic Panniculopathy, Cellulite
Sponsor: Endo Pharmaceuticals

EN3835-304 Protocol Amendment 3 
14 January 2021 
Endo Pharmaceuticals Inc. 
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Endo Pharmaceuticals Inc. 
1400 Atwater Drive 
Malvern, PA 19355 USA 
EN3835 
EN3835-304 
A PHASE 3B, OPEN-LABEL, LONG-TERM STUDY TO 
EVALUATE THE SAFETY AND TEMPORAL PATTERN 
OF RESPONSE OF EN3835 IN THE TREATMENT OF 
EDEMATOUS FIBROSCLEROTIC PANNICULOPATHY 
IND 110077 
NCT03526549 
Amendment 3 
Date: 
Original Protocol: January 31, 2018 
Amendment 1: April 19, 2018 
Amendment 2: November 01, 2018 
Amendment 3: January 14, 2021 
The sponsor of the Investigational New Drug Application (IND) is Endo Global Aesthetics 
Limited (EGAL); however, Endo Pharmaceuticals Inc. (Endo) is authorized to act and to 
communicate on behalf of EGAL. The sponsor is responsible for the conduct of the study, 
analysis of the data, and preparation of the clinical study report.  
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. 
 
NCT #NCT03526549

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2. 
SUMMARY OF CHANGES 
2.1. 
Amendment 3 
EN3835-304 protocol amendment 3 and amended informed consent forms (as necessary) have 
been reviewed and approved by the governing Institutional Review Boards (IRBs) before 
implementation of the amendment at each study center. 
Amendment 3 was incorporated into the protocol on January 14, 2021. The major reason for this 
amendment was that the Sponsor has decided to terminate the EN3835-304 clinical trial at the 
completion of the 3-year time point (Day 1080). The Sponsor will offer voucher(s) for 
commercially approved QwoTM redeemable only for eligible trial participant(s) who will miss 
their potential retreatment due to this decision. The voucher will be offered only for the intended 
benefit to the applicable trial participant, and will cover only the cost of the commercially 
approved QWOTM treatment, applicable for one course of retreatment on the participant’s one or 
two buttocks. This voucher will be offered only if the participant is determined eligible at the 
3-year study visit (Day 1080) following CR-PCSS and PR-PCSS assessments and confirmation 
visit to determine final eligibility. 
Based on the adequate clinical safety and durability data and the long-term safety profile, Endo 
has concluded that the originally proposed 5 year length of the study was overestimated. 
Therefore, Endo has amended the protocol to end the study when all subjects have completed 
their 3 year (Day 1080) visit.  
The major changes to the protocol are outlined below. Revisions in style, minor corrections (such 
as spelling errors, etc), and other minor changes that do not impact content may also have been 
made. 
Section 
Reason for Change/Original Text 
Revision 
Section 3  
Sponsor Contact 
Information 
Updated table to reflect new personnel in 
each role.  
Added contact information for
 
Section 4  
Synopsis 
Updated Study Period. 
Study Period was updated to reflect a new 
estimated date for last subject completed of 
December 2021. 
Section 5.3 
Category I/II 
Subjects – 
Observation 
Assessments 
Updated footnote b. 
Footnote b updated to add new study 
termination date and the opportunity for 
retreatment for study subjects. 
Section 10.1 and 
throughout the 
Protocol 
Study Design 
Updated discussion of observation visits.  
Observation visits have been changed from a 
possible 7 visits to 5 visits to reflect the 
change from a 5-year study to a 3-year study. 
Figure 1 
Study Design 
Study Design Flow Chart was updated.  
Study Design Flow Chart now reflects the 
change from a 5-year study to a 3-year study. 
Section 12 and 
throughout the 
Protocol 
Protocol has been updated to reflect a 3-year 
(36 Month, 1080 Day) design, removing all 
references to study visits or procedures after 
year 3. 
References to year 4 and 5 removed. 

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Section 
Reason for Change/Original Text 
Revision 
Section 18.4 
Study Drug 
Preparation 
Paragraph 2 has been updated. 
Paragraph 2 was reworded to clarify the 
preparation, reconstitution, and storage of 
study drug. 
2.2. 
Amendment 2 
EN3835-304 protocol amendment 2 and amended informed consent forms (as necessary) have 
been reviewed and approved by the governing Institutional Review Boards (IRBs) before 
implementation of the amendment at each study center. 
Amendment 2 was incorporated into the protocol on 01 November 2018. The major reasons for 
this amendment included clarifying entry criteria, clarification of Category II subject 
requirements for retreatment, and to allow subjects who become pregnant to continue in the 
observation portion of the study. The major changes to the protocol are outlined below. 
Revisions in style, minor corrections (such as spelling errors, etc), and other minor changes that 
do not impact content may also have been made. 
Section 
Reason for Change/Original Text 
Revision 
Section 3 
Sponsor Contact 
Information 
 has replaced 
 as 
the Clinical Operations Lead 
 contact information added 
Section 4 
Synopsis 
 
Entire synopsis updated with changes and 
shortened to reduce redundancy. 
Section 5.1 
Schedule of Events 
– Up to 180 Days 
and  
Section 5.2 
Eligible Category 
I/II Subjects – 
Treatment Sessions 
Section 5.3 
Category I/II 
Subjects – 
Observation 
Assessments 
Section 5.4 
Category III 
Subjects-
Assessments,  
Section 12.1 
Study Visits 
Unscheduled visits were removed from all 
Schedules of Events in order to allow the 
investigator to determine the appropriate 
procedures to be done at unscheduled visits 
and to ensure that no photographs or cellulite 
assessments will be done at unscheduled 
visits. 
The Unscheduled visit column has been 
removed from all tables and the statement: 
“Unscheduled visits may be done as deemed 
necessary at any time during the study to 
ensure subject safety; assessments done at 
unscheduled visits are at the discretion of the 
investigator. No photographs or cellulite 
severity assessments will be done at 
unscheduled visits” 
was added to the footnotes for the tables. This 
statement was also added to Section 12.1. 
In addition, the footnotes for each table were 
reordered to ensure consistency and correct 
alphabetical order. 
Section 5.1 
Schedule of Events 
– Up to 180 Days  
Section 12.1.5 
Day 180 Visit 
Visit 1 Day 180b (± 14 days) M6 
Visit 1 Day 180c (± 14 days) M6/Early 
Termination 
The following text was added to footnotec in 
the table and to the text in Section 12.1.5: A 
subject who terminates study participation 
between Day 71 and Day 180 will have an 
Early Termination Visit that includes the 
assessments listed for Visit 1 Day 180. 

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Section 
Reason for Change/Original Text 
Revision 
Section 5.1 
Schedule of Events 
- Up to 180 Days  
Section 14.1.1 
Adverse Events 
 
The following text has been added to footnote 
n in table and to Section 14.1.1: 
Any AE that occurs between the completion 
of studies EN3835-302/303 and the Day 180 
Visit will be reported and evaluated. 
Section 5.4 
Category I/II 
Subjects – 
Observation 
Assessments 
Section 12.2.2.2 
Visits 3-7/ 
EOS/Early 
Termination (Day 
540 – Day 1800/ 
EOS/Early 
Termination 
 
Early Termination was removed from the 
column header for OBS Visit 4 and added to 
the column header for OBS Visit 7 Day 1800 
in the table. Section heading 12.2.2.2 was 
changed to Observation Visits 3-7/EOS/Early 
Termination (Day 540 – Day 1800/ 
EOS/Early Termination 
Section 11.1.1 
Inclusion Criteria – 
All Subjects 
(Through Day 180) 
The following text was deleted: 
5. 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 
 
Section 11.1.2 
Inclusion Criteria - 
Category 1 
Subjects (Post 
Unblinding of 
EN3835-302/303) 
The following text was deleted: 
5. 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. 
The following text was added: 
1. Voluntarily sign and date an informed 
consent agreement. 

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Section 
Reason for Change/Original Text 
Revision 
Section 11.1.3 
Inclusion Criteria - 
Category II 
Subjects (Post 
Unblinding of 
EN3835-302/303) 
1. Received active EN3835 in study 
EN3835-302 or EN3835-303 
2. Maximum composite response at Day 71 
in either or both buttocks in double-blind 
study EN3835-302 or EN3835-303 was at 
least a 2-level composite improvement on 
CR-PCSS/ PR-PCSS 
3. Be willing and able to cooperate with the 
requirements of the study 
4. Be able to read, complete and understand 
the patient reported outcomes rating 
instruments in English 
In order for Category II subjects to continue 
to participate in this study, subjects must: 
1. Voluntarily sign and date an informed 
consent agreement. 
2. Have received active EN3835 in study 
EN3835-302 or EN3835-303. 
3. Have had a composite response at Day 71 
in either or both buttocks in double-blind 
study EN3835-302 or EN3835-303 that was 
at least a 2-level composite improvement on 
CR-PCSS/ PR-PCSS. 
4. Be willing to apply sunscreen to the 
buttocks before each exposure to the sun. 
5. Be judged to be in good health, based upon 
the results of a physical examination, and 
laboratory profile at Screening. 
6. Be willing and able to cooperate with the 
requirements of the study. 
7. Be able to read, complete and understand 
the patient reported outcomes rating 
instruments in English. 
Section 11.1.4 
Inclusion Criteria – 
Category III 
Subjects (Post 
Unblinding of 
EN3835-302/303) 
 
The following text was added: 
1. Voluntarily sign and date an informed 
consent agreement. 
Section 11.1.5 
Inclusion Criteria – 
Category I and 
Category II 
Subjects Who Opt 
for Retreatment 
(Post Unblinding of 
EN3835-302/303) 
1. Voluntarily sign and date an informed 
consent agreement 
2. Subjects who opt for retreatment must 
meet one of the following criterion: 
a. All criteria for Category I subjects; OR 
b. All criteria for Category II subjects, AND 
must have at least one buttock that at Day 71 
in double-blind study EN3835-302 or 
EN3835-303 was at least a 2-level composite 
improvement on CR-PCSS/PR-PCSS that at 
a subsequent visit showed at least a 1-level 
composite reduction of response (ie, a 
reduction in severity by 1-level in both the 
PR-PCSS and CR-PCSS) compared to the 
Day 71 ratings in double-blind study 
EN3835-302/303 in that buttock(s). 
Subjects in Category I and Category II who 
opt for retreatment must meet the following 
additional inclusion criteria to be eligible for 
retreatment. These subjects must: 
1. Voluntarily sign and date an informed 
consent agreement for retreatment. 
2. Be willing to apply sunscreen to the 
buttocks before each exposure to the sun 
while participating in the retreatment portion 
of the study (ie, Treatment Visit 1 through 
Treatment Visit 4). 
3. Be judged to be in good health, based upon 
the results of a physical examination, and 
laboratory profile at Screening.  
4. 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  

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Section 
Reason for Change/Original Text 
Revision 
 
 
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. 
5. Category II subjects must have at least a 1-
level composite response reduction compared 
to Day 71 of the EN3835-302/303 study 
AND no longer maintain a 2-level composite 
response compared to baseline in the 
EN3835-302/303 study on either or both 
buttocks that is confirmed at a Confirmation 
Visit. 
Section 11.2.2 
Exclusion Criteria 
– Category I and 
Category II 
Subjects (Post 
Unblinding of 
EN3835-302/303) 
Original Sections 11.2.2 and 11.2.3 were 
combined and wording updated as outlined 
in revised text. 
A Category I or Category II subject will be 
excluded from study participation if she: 
1. Intends to or has used any of the following 
for the treatment of EFP on a buttock at any 
time during the course of the study: 
a. Liposuction in a buttock. 
b. Injections (eg, mesotherapy); 
radiofrequency device treatments; laser 
treatment; buttock implant treatment; 
cryolipolysis; or surgery (including subcision 
and/or powered subcision) within a buttock. 
c. Any investigational drug or treatment for 
EFP on a buttock (other than treatment in 
study EN3835-302/303). 
d Endermologie or similar treatments within 
a buttock. 
e. Massage therapy within a buttock during 
the 3 month period before observational visit. 
f. Creams (eg, Celluvera, TriLastin) and/or 
home therapies to prevent or mitigate EFP 
within a buttock during the 2-week period 
before observational visit. 
2. Has received any collagenase treatments at 
any time since completion of the double-
blind study 
3. Any other condition(s) that, in the 
Investigator’s opinion, might indicate that the 
subject is unsuitable for the study. 
Section 11.2.4 
Exclusion Criteria 
Category I and II 
Subjects Who Opt 
to Receive 
Retreatment (Post 
Unblinding of 
EN3835-302/303)  
Formerly Section 
11.2.5 
5. Prior to and during the course of 
retreatment (Treatment Visit 1 through 
Treatment Visit 4), is nursing or providing 
breast milk 
6. Prior to and during the course of 
retreatment (Treatment Visit 1 through 
Treatment Visit 4), intends to become 
pregnant during the study 
4. Is nursing or providing breast milk within 
30 days prior to and/or during the course of 
retreatment (Treatment Visit 1 through 
Treatment Visit 4). 
5. Is pregnant or intends to become pregnant 
during the course of retreatment (Treatment 
Visit 1 through Treatment Visit 4). 

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Section 
Reason for Change/Original Text 
Revision 
Section 12.1.2 
Subject Screening 
The following text has been deleted: 
All potential subjects eligible for screening 
in EN3835-304 will be pre-populated in the 
electronic data capture (EDC) system. If the 
Screening Visit for a subject is within 
14 days of the subject’s Day 71 of study 
EN3835-302/303, the Screening Visit 
assessments for a subject will be pre-
populated by a data transfer of the results of 
assessment of Day 71 (and height and 
Fitzpatrick scale rating of Day 1) of study 
EN3835-302/303 for that subject. 
 
Section 12.1.2 
Subject Screening 
If the Screening Visit for a subject is greater 
than 14 days of the subject’s Day 71 of study 
EN3835-302/303, the Screening Visit 
assessments will be performed as detailed in 
Section 5.1 with only the subject ID and 
Fitzpatrick scale rating transferring from 
Day 1 of study EN3835-302/303 and pre-
populating the EDC of study EN3835-304. 
All changes in medical history occurring 
between completion of study 
EN3835-302/303 and the Screening Visit of 
study EN3835-304 will be considered 
adverse events and 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). 
If the Screening Visit for a subject is greater 
than 14 days after the subject’s Day 71 of 
study EN3835-302/303, only the unique 
Screening Visit assessments will be 
performed (informed consent, inclusion and 
exclusion criteria evaluation, height, and 
physical examination). No subject will be 
allowed to enroll in the study if the Screening 
Visit does not occur within 180 days after 
Day 71 of Study EN3835-302/303. All 
changes in medical history occurring between 
completion of study EN3835-302/303 and the 
Screening Visit of study EN3835-304 will be 
considered adverse events and 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). 
Section 12.1.3 
Medical History 
Since this is a long-term rollover study for 
subjects that participated and completed the 
double-blind study (EN3835-302 or 
EN3835-303), in which the subjects’ medical 
history was collected; there will be no 
medical history collected for study 
EN3835-304. 
Since this is a long-term rollover study for 
subjects that participated and completed the 
double-blind study (EN3835-302 or 
EN3835-303), in which the subjects’ medical 
history was collected, only newly discovered 
medical history (events/procedures that 
occurred prior to enrollment in study 
EN3835-302/303) will be collected (eg, a 
subject remembers having an appendectomy 
as a child that was not reported in the medical 
history for EN3835-302/303). 
Section 12.1.5  
Day 180/Early 
Termination Visit 
(Screening B) 
Category II subjects that have lost 1-
composite level of response (ie, at least a 
1-level worsening of both PR-PCSS and 
CR-PCSS in at least one buttock). If there is 
a composite worsening of cellulite severity 
of 1-level (ie, worsening of both the 
PR-PCSS and CR-PCSS by at least 1 
severity levels) detected in a Category II 
subject, the confirmation of loss of response 
will be established during a follow-up visit 
~2 weeks after the loss of response is 
detected at Day 180 as described in 
Section 12.2.2.3 (Confirmation Visit). 
If the subject is categorized to a classification 
and has ratings that qualify for retreatment 
(ie, all Category I subjects will be offered 
retreatment; Category II subjects that have 
lost 1-composite level of response (ie, at least 
a 1-level composite response reduction 
compared to Day 71 of the EN3835-302/303 
study AND no longer maintain a 2-level 
composite response compared to baseline in 
the EN3835-302/303 study on either or both 
buttocks). If there is a composite worsening 
of cellulite severity of 1-level detected in a 
Category II subject, the confirmation of loss 

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Section 
Reason for Change/Original Text 
Revision 
 
 
of response will be established during a 
follow-up visit ~2 weeks after the loss of 
response is detected at Day 180 as described 
in Section 12.2.2.3 (Confirmation Visit). 
Section 12.1.5  
Day 180/Early 
Termination 
(Screening B) 
 
The following text has been added to allow 
for multiple screening B visits: 
If a subject does not meet Screening B 
criteria (eg, positive pregnancy test, elevated 
liver enzymes, etc), the subject maybe 
rescreened at a later date. 
Section 12.2 
Category I Subjects 
and Category II 
Subject Visits (Post 
Unblinding of 
EN3835-302/303) 
Category II subjects who have shown a 
1-level composite reduction of response 
compared to their Day 71 from 
EN3835-302/302 improvement will be 
offered a course of retreatment;… 
Category II subjects who have had at least a 
1-level composite response reduction 
compared to Day 71 of the EN3835-302/303 
study AND no longer maintain a 2-level 
composite response compared to baseline in 
the EN3835-302/303 study will be offered a 
course of retreatment; 
Section 12.2.1.2 
Selecting and 
Marking Dimples 
During Treatment 
Visits 
Category I subjects and Category II subjects 
eligible for retreatment can receive up to 3 
retreatment visits of study drug as outlined in 
Section 5.2 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. 
Category I subjects and Category II subjects 
eligible for retreatment can receive up to 3 
retreatment visits of study drug as outlined in 
Section 5.2 unless the buttock is dimple-free 
(score of 0 on CR-PCSS as reported by the 
Investigator) at Treatment Visit 1, Treatment 
Visit 2 and/or Treatment Visit 3. 
Section 13.1.2.4 
Subject Satisfaction 
with Cellulite 
Treatment 
Assessment 
 
The following text was added: 
The subject will view each of their 
pretreatment Day 1 digital images from the 
double-blind study (EN3835-302/303) 
alongside their current study visit digital 
images of their buttocks to aid in the 
assessment. 
Section 14.6.3 
Pregnancy 
A subject who becomes pregnant must be 
withdrawn from the study. 
A subject who becomes pregnant must be 
withdrawn from study treatment (if 
applicable) and will not be eligible for 
retreatment while pregnant, but may remain 
in the study for observational purposes and 
may be considered for retreatment, if eligible, 
when no longer pregnant or breastfeeding. 
Section 17.2.3 
Time to Reduction 
of Response (TRR) 
Population 
 
The following text has been added: 
TRR will be evaluated separately for subjects 
who had a 1-level and 2-level composite 
improvement in CR-PCSS and PR-PCSS 
during studies EN3835-302/303 in each 
buttock. 
Section 17.4 
Demographic and 
Other Baseline 
Characteristics 
The following text has been deleted: 
These data will be transferred from 
EN3835-302 and EN3835-303 and will pre-
populate the relevant fields of the database 
for this open-label study. 
 

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2.3. 
Amendment 1 
EN3835-304 protocol amendment 1 and amended informed consent forms (as necessary) have 
been reviewed and approved by the governing Institutional Review Boards (IRBs) before 
implementation of the amendment at each study center. 
Amendment 1 was incorporated into the protocol on April 19, 2018. The major reasons for this 
amendment were the need to revise the eligibility criteria and the need to revise the timing for 
retreatment of Category I and eligible Category II subjects (ie, 1-level and 2-level responders at 
Day 71 of the double-blind studies, respectively), adding the potential of an unscheduled visit, 
conducting additional cellulite assessments, and eliminating reclassification of subjects. 
Section 
Original Text 
Revised Text 
Title Page 
EN3835-304: A Phase 3b, Open-label, 
Long-term Study to Evaluate the Safety and 
Durability of Response of EN3835 in the 
Treatment of Edematous Fibrosclerotic 
Panniculopathy 
EN3835-304: A Phase 3b, Open-label, 
Long-term Study to Evaluate the Safety and 
Temporal Pattern of Response of EN3835 in 
the Treatment of Edematous Fibrosclerotic 
Panniculopathy 
Section 3 
Sponsor Contact 
Information, 
Clinical 
Development Lead 
 
, Clinical Development  
Office: 
 
Cell:  
 
Email: 
 
 
, Clinical Development 
Office: 
 
Cell:  
 
Email: 
 
Section 3 
Sponsor Contact 
Information, 
Medical Monitor 
 
Office:  
 
Cell:  
 
Email: 
 
 
 Clinical Development 
Office: 
  
Cell: 
 
Email: 
 
Section 4  
Synopsis, Title of 
Study 
A Phase 3b, Open-Label, Long-Term Study 
To Evaluate The Safety And Durability of 
Response of EN3835 in the Treatment of 
Edematous Fibrosclerotic Panniculopathy 
A Phase 3b, Open-label, Long-Term Study to 
Evaluate the Safety and Temporal Pattern of 
Response of EN3835 in the Treatment of 
Edematous Fibrosclerotic Panniculopathy 
Section 4 
Synopsis, Study 
Period 
Estimated date last subject completed: 
October-2023 (est) 
Estimated date last subject completed: 
October-2023 
Section 4 
Synopsis, Objective 
To assess the safety, long-term 
immunogenicity profile, and durability of 
response of EN3835 in the treatment of 
edematous fibrosclerotic panniculopathy 
(EFP), commonly known as cellulite, in 
adult women 
To assess the safety, long-term 
immunogenicity profile, and TRR of EN3835 
in the treatment of edematous fibrosclerotic 
panniculopathy (EFP), commonly known as 
cellulite, in adult women 
Section 4 
Synopsis, Study 
Design 
This study is a Phase 3b rollover, long-term 
study to assess the safety and duration of 
efficacy of EN3835 in the treatment of EFP. 
To be eligible, a subject must have 
participated in and completed the previous 
Phase 3 cellulite study EN3835-302 or 
EN3835-303. Subjects will be screened for 
study eligibility during the Day 71 Visit of 
their respective double-blind trial and will be 
offered enrollment into the trial for 
continued durability of response and/or 
safety for a period of up to 5 years. 
This study is a Phase 3b rollover, long-term 
study to assess the safety and TRR of 
EN3835 in the treatment of EFP. To be 
eligible, a subject must have participated in 
and completed the previous Phase 3 cellulite 
study EN3835-302 or EN3835-303. Subjects 
will be screened for study eligibility during 
the Day 71 Visit of the respective 
double-blind trial in which the subject 
participated. Subjects will be offered 
enrollment into this trial to observe and 
record continued evaluation of response to 

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Section 
Original Text 
Revised Text 
Following unblinding of the double-blind 
studies, subjects who received placebo 
during the double-blind study will be 
discontinued, and subjects who received 
active EN3835 will be stratified into 
3 categories: 
EN3835 and/or safety for a period of up to 
5 years after their initial injection in the 
double-blind study EN3835-302 or 
EN3835-303. Following unblinding of the 
double-blind studies, subjects who received 
placebo during the double-blind study will be 
discontinued, and subjects who received 
active EN3835 will be classified into one of 
three categories: 
Category I: 1-level Composite Responders 
Category I: 1-Level Composite Responders 
Category I subjects will be eligible for one 
additional retreatment course in up to two 
buttocks in the current open-label study, 
beginning on Day 360 (ie, approximately 
1 year after Day 71 of the double-blind 
studies). 
Category I subjects will be eligible for one 
additional retreatment course in up to two 
buttocks concurrently in this open-label 
study, retreatment can begin after 
assessments on Day 180 (ie, approximately 
6 months after Day 71 of the double-blind 
studies) and after unblinding of the 
double-blind studies confirms the subject 
received active EN3835. Operationally, 
eligible subjects who qualify for Category I 
status but choose NOT to receive additional 
retreatment will be followed with 
observational assessments. 
Category II will include subjects who 
showed an improvement in cellulite severity 
of at least two levels in at least one buttock 
in both the PR-PCSS and the CR-PCSS 
(ie, 2-level composite responder) in 
EN3835-302 or EN3835-303. These subjects 
will be observed for continued durability of 
response (defined below) approximately 
every 6 months, and will be observed for 
safety annually for up to 5 years (Day 1800). 
Category II subjects will not be eligible for 
retreatment. In the event a Category II 
subject shows a composite loss of efficacy 
back to baseline severity levels observed 
prior to treatment in the double-blind study, 
they will be re-categorized as Category III 
for continued safety assessments. 
Category II will include subjects who showed 
an improvement in cellulite severity of at 
least two levels in at least one buttock in both 
the PR-PCSS and the CR-PCSS (ie, 2-level 
composite responder) in EN3835-302 or 
EN3835-303. These subjects will be 
observed for continued response to EN3835 
and safety approximately every 6 months 
during the first two years and thereafter 
annually for up to 5 years (Day 1800). In the 
event a Category II subject shows a 
composite loss of efficacy of 1-level 
(ie, reduction of response by 1-level in the 
PR-PCSS and 1-level in the CR-PCSS 
compared to Day 71 ratings in the 
double-blind study), they will be offered 
retreatment. Operationally, Category II 
subjects who show a 1-level composite 
reduction in CR-PCSS and PR-PCSS, but 
chose NOT to receive additional retreatment, 
will be followed for observational 
assessments. 
Subjects will be assessed for safety on each 
day of injection during retreatment, and at 
71 days after initiation of retreatment, and 
assessed for cellulite severity 22, 43, and 
71 days following initiation of retreatment. 
Subjects will be assessed for safety on each 
day of injection during retreatment, and at 
Treatment Visit 4 (Day 71) and assessed for 
cellulite severity on Treatment Visits 1, 2, 3, 
and 4 (Treatment Phase Days 1, 22, 43, and 
71). Subjects will be offered one and only 
one retreatment course in up to 2 eligible 
buttocks concurrently during this 5-year 
long-term study. 

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Operationally, eligible subjects who qualify 
for Category I status but choose NOT to 
receive additional retreatment will be 
followed as Category III subjects, with 
annual safety assessments. 
Deleted 
Category III subjects will include all other 
subjects who received active EN3835 in 
study EN3835-302 or EN3835-303 but did 
not meet criteria to be included in Category I 
or II (ie, non-composite responders) at the 
time of categorical assignment. These 
subjects will be observed annually for safety 
for up to 5 years (Day 1800), and will not be 
eligible for retreatment during the study. As 
noted above, Category III will also include 
any subjects originally designated as 
Category II, but show a composite loss of 
efficacy back to baseline levels during the 
course of the study. 
Category III subjects will include all other 
subjects who received active EN3835 in 
study EN3835-302 or EN3835-303 but did 
not meet criteria to be included in Category I 
or II (ie, non-composite responders) at the 
time of categorical assignment. These 
subjects will be observed for safety every 
6 months for two years and then annually for 
up to 5 years (Day 1800), and will not be 
eligible for retreatment during the study.  
For study purposes, durability of response 
will be assessed as the continuation of at 
least a 2-level composite improvement in 
cellulite severity compared to the baseline 
level established during the double-blind 
study as assessed by both the PR-PCSS and 
the CR-PCSS until loss of response. Loss of 
response is defined as a composite 
worsening of cellulite severity back to 
baseline levels (on both the PR-PCSS and 
CR-PCSS), and confirmation of loss of 
response will be established during a 
follow-up visit ~2 weeks after the loss of 
response is first detected. The duration of 
response for composite 1-level responders 
(ie, Category I) will also be assessed at 
180 days after the Day 71 Visit of the 
double-blind study. 
For study purposes, reduction of response is 
defined as a composite worsening of cellulite 
severity improvement, and confirmation of 
reduction of response will be established 
during a follow-up visit (Durability 
Confirmation Visit) ~2 weeks after the 
reduction of response is first detected. TRR is 
defined as the time from assessing efficacy 
(Day 71 of double-blind study) to the study 
visit at which a composite 1-level loss of 
response in both PR-PCSS and CR-PCSS is 
observed. Durability of response is defined as 
a complete loss of response in which cellulite 
severity returns back to baseline levels (on 
both the PR-PCSS and CR-PCSS). 
Section 4 
Synopsis, Number 
of Subjects 
(Planned) 
Up to approximately 420 
Up to approximately 420 active subjects 
Section 4 
Synopsis, 
Diagnosis and 
Inclusion/ 
Exclusion Criteria, 
All Subjects 
(Through 
Day 180): Inclusion 
Criteria 
2. Have participated in and completed the 
double-blind Phase 3 study EN3835-302 or 
EN3835 303 
2. Have participated in and completed the 
double-blind Phase 3 study EN3835-302 or 
EN3835-303 (ie, assessed safety and 
obtained PR-PCSS and CR-PCSS ratings at 
Day 71/EOS of the double-blind study; does 
not include early termination subjects). 
3. Be willing to apply sunscreen to any 
treated area before each exposure to the sun 
while participating in the study during this 
period 
3. Be willing to apply sunscreen to both 
buttocks before each exposure to the sun 
while participating in the study during this 
period 

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4. Be judged to be in good health, based 
upon the results of a medical history, 
physical examination, and laboratory profile 
at Screening 
4. Be judged to be in good health, based 
upon the results of a physical examination, 
and laboratory profile at Screening 
Section 4 
Synopsis, 
Diagnosis and 
Inclusion/ 
Exclusion Criteria, 
All Subjects 
(Through 
Day 180): 
Exclusion Criteria  
1. Intends to or has used any of the 
following for the treatment of EFP on a 
buttock at any time during the course of the 
study, including (but not limited to): 
1. Intends to or has used any of the following 
for the treatment of EFP on a buttock at any 
time during the time period from Day 71 of 
double-blind study EN3835-302 or 
EN3835-303 through Day 180 Visit in study 
EN3835-304 (approximately 6 months after 
Day 71 of study EN3835-302 or 
EN3835-303, including (but not limited to): 
a.  Liposuction in a buttock during the 
12-month period before injection of study 
drug 
a.  Liposuction in a buttock  
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 
b. Injections (eg, mesotherapy); 
radiofrequency device treatments; laser 
treatment; buttock implant treatment; 
cryolipolysis; or surgery (including subcision 
and/or powered subcision) within a buttock  
c.  Any investigational treatment for EFP on 
a buttock during the 12-month period before 
injection of study drug 
c.  Any investigational treatment for EFP on 
a buttock, other than the treatment received 
in study EN3835-302/303 
d.  Endermologie™ or similar treatments 
within a buttock during the 6-month period 
before injection of study drug 
d.  Endermologie™ or similar treatments 
within a buttock 
e.  Massage therapy within a buttock during 
the 3-month period before injection of study 
drug 
e.  Massage therapy within a buttock  
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 
f.  Creams (eg, Celluvera™, TriLastin®) 
and/or home therapies to prevent or mitigate 
EFP within a buttock  
3.  Has received an investigational drug or 
treatment within 30 days before injection of 
study drug 
3.  Has received or intends to receive an 
investigational drug or treatment, other than 
the treatment received in study EN3835-
302/303 during this period 
 
NOTE: After unblinding of EN3835-302/ 
303, subjects who received EN3835 in 
EN3835-302 or EN3835-303 will be placed 
into one of 3 categories based on their 
responder status. For each category, the 
following Inclusion and Exclusion Criteria 
apply beyond Day 180: 
NOTE: After Day 180 Visit assessments are 
completed in study EN3835-304 and 
unblinding of EN3835-302/303, subjects who 
received EN3835 in EN3835-302 or 
EN3835-303 will be placed into one of three 
categories based on their responder status of 
each of their buttocks at Day 71 in study 
EN3835-302 or EN3835-303. Investigators, 
subjects and all site personnel will be blinded 
to the treatment that the subjects received in 
the double-blind studies until assessments at 
the Day 180 visit of study EN3835-304 are 
completed; even if this visit occurs after the 
EN3835-302/303 studies are unblinded by 

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Endo. Investigator, subjects and site 
personnel will be unblinded on Day 180 of 
study EN3835-304 after Day 180 
assessments are completed or at an 
Unscheduled Visit, pending when database 
lock and unblinding of studies EN3835-302/ 
303 occurs relative to Day 180 of this current 
study EN3835-304. For each category, the 
following Inclusion and Exclusion Criteria 
apply beyond the day that the investigator, 
subject, and site personnel are unblinded: 
Section 4 
Synopsis, 
Diagnosis and 
Inclusion/ 
Exclusion Criteria, 
Category I 
Subjects: Inclusion 
Criteria 
2. Maximum composite response in either 
or both buttocks in double-blind study 
EN3835-302 or EN3835-303 was ONLY a 
1-level improvement on CR-PCSS/ 
PR-PCSS 
2. Maximum composite response at Day 71 
in either or both buttocks in double-blind 
study EN3835-302 or EN3835-303 was 
ONLY a 1-level improvement on 
CR-PCSS/PR-PCSS 
3. Prior to retreatment, at least one buttock 
having: 
a. a score of ≥2 (mild) as reported by the 
subject (PR-PCSS) and 
b. a score of ≥2 (mild) as reported by the 
Investigator (CR-PCSS) 
Deleted 
4. Be willing to apply sunscreen to the 
buttocks before each exposure to the sun 
while participating in the retreatment portion 
of the study (ie, Visit 2 through Visit 6) 
3. Be willing to apply sunscreen to the 
buttocks before each exposure to the sun 
while participating in the retreatment portion 
of the study (ie, Treatment Visit 1 through 
Treatment Visit 4) 
5. Be judged to be in good health, based 
upon the results of a medical history, 
physical examination, and laboratory profile 
at Screening 
4. Be judged to be in good health, based 
upon the results of a physical examination, 
and laboratory profile at Screening 
Section 4 
Synopsis, 
Diagnosis and 
Inclusion/ 
Exclusion Criteria, 
Category I 
Subjects: Exclusion 
Criteria 
Added 
Exclusion Criteria for Subjects Whom opt for 
Observations Only (ie, no retreatment): None 
A Category I subjects will not receive 
additional treatments and will be 
re-categorized to Category III status if she: 
1. Is unwilling to receive one additional 
course of open-label retreatment (3 treatment 
visits) for EFP with EN3385 
2. 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 
Deleted 

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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 
3. 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. Requires the following concomitant 
medications before or during participation in 
retreatment portion 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 
5. 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 since completion 
of the double-blind study 
b. Injections (eg, mesotherapy); 
radiofrequency device treatments; laser 
treatment; buttock implant treatment; 
cryolipolysis; or surgery (including 
subcision and/or powered subcision) within a 
buttock since completion of the double-blind 
study 
c. Any investigational treatment for EFP on 
a buttock since completion of the double-
blind study 
d. Endermologie™ or similar treatments 
within a buttock since completion of the 
double-blind study 
 

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e. Massage therapy within a buttock during 
the 3-month period before retreatment with 
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 retreatment with study drug  
6. Prior to and during the course of 
retreatment (Visit 2 through Visit 6), is 
presently nursing or providing breast milk 
7. Prior to and during the course of 
retreatment (Visit 2 through Visit 6), intends 
to become pregnant during the study 
8. Prior to and during the course of 
retreatment (Visit 2 through Visit 6), intends 
to use tanning spray or tanning booths during 
the study 
9. Has received an investigational drug or 
treatment within 30 days before retreatment 
with study drug 
10. Has a known systemic allergy to 
collagenase or any other excipient of study 
drug 
11. Has received any collagenase treatments 
at any time since completion of the double-
blind study 
12. Any other condition(s) that, in the 
Investigator’s opinion, might indicate the 
subject to be unsuitable for Category I 
retreatment 
Section 4 
Synopsis, 
Diagnosis and 
Inclusion/ 
Exclusion Criteria, 
Category II 
Subjects: Inclusion 
Criteria 
2. Maximum composite response in either 
or both buttocks in double-blind study 
EN3835-302 or EN3835-303 was at least a 
2-level composite improvement on 
CR-PCSS/PR-PCSS 
2. Maximum composite response at Day 71 
in either or both buttocks in double-blind 
study EN3835-302 or EN3835-303 was at 
least a 2-level composite improvement on 
CR-PCSS/PR-PCSS 
Section 4 
Synopsis, 
Diagnosis and 
Inclusion/ 
Exclusion Criteria, 
Category II 
Subjects: Exclusion 
Criteria 
Added 
Exclusion Criteria for Subjects Whom opt for 
Observation Only (ie, no retreatment):  
1.  Intends to or has used any of the 
following for the treatment of EFP on a 
buttock at any time during the course of the 
study: 
1.  Intends to or has used any of the following 
for the treatment of EFP on a buttock at any 
time during the course of the study: 
a.  Liposuction in a buttock during the 
12-month period before injection of study 
drug 
a.  Liposuction in a buttock  
b.  Injections (eg, mesotherapy); 
radiofrequency device treatments; laser 
treatment; buttock implant treatment; 
cryolipolysis; or surgery (including 
subcision and/or powered subcision) within a 
b.  Injections (eg, mesotherapy); 
radiofrequency device treatments; laser 
treatment; buttock implant treatment; 
cryolipolysis; or surgery (including subcision 
and/or powered subcision) within a buttock  

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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 
c.  Any investigational drug or treatment for 
EFP on a buttock (other than treatment in 
study EN3835-302/303) 
d.  Endermologie™ or similar treatments 
within a buttock during the 6-month period 
before injection of study drug 
d.  Endermologie™ or similar treatments 
within a buttock  
e.  Massage therapy within a buttock during 
the 3-month period before injection of study 
drug 
e.  Massage therapy within a buttock during 
the 3-month period before observational visit 
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 
f.  Creams (eg, Celluvera™, TriLastin®) 
and/or home therapies to prevent or mitigate 
EFP within a buttock during the 2-week 
period before observational visit 
2.  Has received an investigational drug or 
treatment within 30 days before injection of 
study drug 
2.  Has received an investigational drug or 
treatment (other than treatment in study 
EN3835-302/303) 
3.  Any other condition(s) that, in the 
Investigator’s opinion, might indicate the 
subject to be unsuitable for the study 
3.  Any other condition(s) that, in the 
Investigator’s opinion, might indicate the 
subject to be unsuitable for the study 
Section 4 
Synopsis, 
Diagnosis and 
Inclusion/ 
Exclusion Criteria, 
Retreatment 
Subjects (Eligible 
Subjects Whom opt 
to Receive 
Retreatment): 
Inclusion Criteria 
Added 
Retreatment Subjects (Eligible Subjects 
Whom opt to Receive Retreatment):  
Inclusion Criteria: 
1. Voluntarily sign and date an informed 
consent agreement 
2. Subjects who opt for retreatment must 
meet one of the following criterion:  
a.  All criteria for Category I subjects; OR 
b. All criteria for Category II subjects, AND 
must have at least one buttock that at Day 71 
in double-blind study EN3835-302 or 
EN3835-303 was at least a 2-level composite 
improvement on CR-PCSS/PR-PCSS that at 
a subsequent visit showed at least a 1-level 
composite reduction of response (ie, a 
reduction in severity by 1-level in both the 
PR-PCSS and CR-PCSS) compared to the 
Day 71 ratings in double-blind study 
EN3835-302/303 in that buttock(s). 
Section 4 
Synopsis, 
Diagnosis and 
Inclusion/ 
Exclusion Criteria, 
Retreatment 
Subjects (Eligible 
Subjects Whom opt 
to Receive 
Retreatment): 
Exclusion Criteria 
Added 
Retreatment Subjects (Eligible Subjects 
Whom opt to Receive Retreatment): 
Exclusion Criteria: 
1.  Has any of the following systemic 
conditions: 
a.  Coagulation disorder 
b.  Evidence or history of malignancy (other 
than excised basal-cell or squamous-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 
retreatment portion the trial: 
a. Anticoagulant or antiplatelet medication or 
has received anticoagulant or antiplatelet 
medication (except for ≤150 mg aspirin 
daily) within 7 days before or 7 days after 
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 since completion 
of the double-blind study 
b. Injections (eg, mesotherapy); 
radiofrequency device treatments; laser 
treatment; buttock implant treatment; 
cryolipolysis; or surgery (including subcision 
and/or powered subcision) within a buttock 
since completion of the double-blind study 
c. Any investigational treatment for EFP on 
a buttock since completion of the 
double-blind study 
d. Endermologie™ or similar treatments 
within a buttock since completion of the 
double-blind study 

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e. Massage therapy within a buttock during 
the 3-month period before retreatment with 
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 retreatment with study drug 
5. Prior to and during the course of 
retreatment (Treatment Visit 1 through 
Treatment Visit 4), is nursing or providing 
breast milk 
6. Prior to and during the course of 
retreatment (Treatment Visit 1 through 
Treatment Visit 4), intends to become 
pregnant during the study 
7. Prior to and during the course of 
retreatment (Treatment Visit 1 through 
Treatment Visit 4), intends to use tanning 
spray or tanning booths during the study 
8. Has received an investigational drug or 
treatment, other than treatment in study EN-
3835-302/303, within 30 days before 
retreatment with study drug 
9. Has a known systemic allergy to 
collagenase or any other excipient of study 
drug 
10. Has received any collagenase treatments 
at any time since completion of the double-
blind study 
11. Any other condition(s) that, in the 
Investigator’s opinion, might indicate the 
subject to be unsuitable for retreatment 
Section 4 
Synopsis, 
Investigational 
Product, Dosage 
and Mode of 
Administration 
EN3835, up to 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 
qualifying buttock, for a total dose of up to 
1.68 mg and a total volume of up to 7.2 mL 
(3.6 mL per buttock). Total number of 
injections will be up to 24 injections per 
treatment visit in up to two buttocks (ie, up 
to 12 injections per buttock). For subjects 
that qualify for retreatment, there will be 
3 treatment visits at 21 days intervals, 
beginning 1 year after initial exposure to 
EN3835 in their respective double-blind 
study (EN3835-302/303). 
EN3835, up to 1.68 mg, subcutaneous. A 
dose of 0.84 mg of EN3835 per buttock will 
be administered as 12 subcutaneous 
injections (0.3-mL injections administered as 
three 0.1-mL aliquots per injection) in each 
qualifying buttock, for a total dose of up to 
1.68 mg and a total volume of up to 7.2 mL 
(3.6 mL per buttock). Total number of 
injections will be up to 24 injections per 
treatment visit in up to two buttocks 
(ie, 12 injections per buttock). For subjects 
that qualify for retreatment, there will be 
3 treatment visits at 21 day intervals, 
beginning 6 months after Day 71in their 
respective double-blind study 
(EN3835-302/303). 
Section 4 
Synopsis, Duration 
of Study 
For subjects rolling over from EN3835-302/ 
303: Up to sixty (60) months from first 
exposure to EN3835 in study 
EN3835-302/303. 
Screening Phase: Up to 14 days 
For subjects rolling over from EN3835-302/ 
303: Up to sixty (60) months from Day 71 
(approximately 28 days after their last 
exposure to EN3835) of the study 
EN3835-302/303. 

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Screening Phase: Up to 14 days 
Observational Phase: Subjects completing 
double-blind studies EN3835-302 or 
EN3835-303 will be assessed at visits that 
occur approximately every 6 months 
following their last visit in the double-blind 
study. Following unblinding of studies 
EN3835-302/EN3835-303, subjects who 
received placebo will be discontinued after 
Day 180. The durability of response in 
subjects with a ≥1-level composite 
PR-PCSS/CR-PCSS improvement will be 
assessed at 180 days, however durability of 
response beyond Day 180 will be assessed in 
subjects that received active EN3835 in one 
of the double-blind studies and showed at 
least a 2-level composite PR-PCSS/ 
CR-PCSS improvement (ie, reduction) in 
cellulite severity. All subjects who received 
active EN3835 in the double-blind study will 
be assessed for safety for up to 5 years 
(1800 days). 
Observational Phase: Subjects completing 
double-blind studies EN3835-302 or 
EN3835-303 will be assessed at visits that 
occur approximately every 6 months for two 
years and thereafter annually for up to 
5 years following their last visit in the 
double-blind study. Following unblinding of 
studies EN3835-302/EN3835-303 and after 
Day 180 assessments have been completed in 
study EN3835-304, subjects who received 
placebo will be discontinued. The TRR in 
subjects with a ≥1-level composite 
PR-PCSS/CR-PCSS improvement will be 
assessed at Day 180 in study EN3835-304, 
however TRR beyond Day 180 will be 
assessed in subjects that received active 
EN3835 in one of the double-blind studies or 
in the open-label study EN3835-304 and 
showed at least a 1-level composite 
PR-PCSS/CR-PCSS improvement 
(ie, reduction) in cellulite severity. All 
subjects who received active EN3835 in the 
double-blind study will be assessed for safety 
for up to 5 years (1800-days) after Day 71 of 
the double-blind studies (EN3835-302 or 
EN3835-303). 
Section 4 
Synopsis, Criteria 
for Evaluation 
PR-CIS: a subject reported scale to 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 
from 0 (not at all) to 10 (extremely). A 
PR-CIS total score and an abbreviated 
PR-CIS score (excluding question 5) will be 
derived from these 6 individual questions. 
PR-CIS: Patient Reported Cellulite Impact 
Scale to assess 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 
from 0 (not at all) to 10 (extremely). A 
PR-CIS total score and an abbreviated 
PR-CIS score (excluding question 5) will be 
derived from these 6 individual questions. 
Added text 
Subject Global Aesthetic Improvement Scale 
(S-GAIS): 7-level scale ranging from 3 (very 
much improved) to −3 (very much worse) 
Subject Satisfaction with Cellulite Treatment 
Assessment: 5-level scale ranging from 2 
(very satisfied) to −2 (very dissatisfied) for 
both the target and non-target buttocks 
Subject Satisfaction with Cellulite Treatment 
Assessment: 5-level scale ranging from 2 
(very satisfied) to −2 (very dissatisfied) 
Section 4 
Synopsis, Criteria 
for Evaluation 
Durability of 2-Level Composite Response: 
• For the purposes of this study, treatment of 
EFP with EN3835 is considered 2-level 
composite responder once subjects show an 
improvement of at least 2 levels on each 
assessment scale (CR-PCSS/PR-PCSS) at 
the same visit during the double-blind study 
at or before Day 71 in either or both 
buttocks. The duration of response is 
Time to Reduce a 2-Level Composite 
Response: 
• For the purposes of this study, a subject 
treated with EN3835 is considered a 2-level 
composite responder once an improvement of 
at least 2 levels on each assessment scale 
(PR-PCSS/CR-PCSS) is shown at the same 
visit during the double-blind study at or 
before Day 71 in either or both buttocks. The 

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considered to end once a subject’s cellulite 
severity returns to baseline on both the CR-
PCSS and PR-PCSS. 
All cellulite assessments will be done by 
treated areas. Each treatment area 
(eg, left/right buttock) will be evaluated 
separately. 
time until a reduction of response has 
occurred is considered to end once a 
subject’s cellulite severity improvement 
reduces a composite 1-level, ie, a reduction 
in severity by 1-level in both the PR-PCSS 
and CR-PCSS. 
Cellulite assessments of PR-PCSS, 
CR-PCSS, and S-GAIS will be performed on 
each buttock. Each buttock will be evaluated 
separately. Cellulite assessment of PR-CIS, 
Subject satisfaction with cellulite treatment 
assessment, and SSRS will be performed on 
both buttocks.  
Section 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; and local adverse events 
associated with the injection site, including 
bruising, pain, nodules/mass, ulceration, 
erythema, pruritus, swelling, and/or 
induration) 
• Clinical laboratory tests (at retreatment 
visits and 28 days after last dose) 
• 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, and/or any 
hypersensitivity reactions, including 
anaphylaxis; and local adverse events 
associated with the injection site, including 
acute (eg, erythema, bruising, pain, 
nodules/mass, ulceration, blistering, pruritus, 
swelling, and/or induration) and/or chronic 
(eg, skin thickening, fibrosclerosis, peau 
d’orange changes) cutaneous adverse events 
• Clinical laboratory tests (prior to 
retreatment visits and 28 days after last 
retreatment dose) 
Section 4 
Synopsis, 
Statistical Methods: 
Analysis 
Population 
For subjects entering open-label study 
period, subjects who received active EN3835 
in their double-blind studies (EN3835-302/ 
303) will be classified into 3 categories: 
Category I: 1-level Composite Responders 
Category II: 2-Level Composite Responders 
Category III: Non-Composite Responders 
Based on subject category, two (2) 
populations are considered in the statistical 
analysis of the study: overall safety 
population and durability population. 
For subjects entering the open-label study 
period, subjects who received active EN3835 
in the double-blind studies (EN3835-302/ 
303) will be classified into 3 categories: 
Category I: 1-Level Composite Responders 
Category II: 2-Level Composite Responders 
Category III: Non-Composite Responders 
Based on subject category, two (2) 
populations are considered in the statistical 
analysis of the study: overall safety 
population and TRR population. 
Section 4 
Synopsis, 
Statistical Methods: 
Overall Safety 
Population 
The overall safety population is defined as 
all rollover subjects who enter the open-label 
study period. This population will include all 
Category I, II, and III subjects. In addition, 
the safety data will be summarized by 
treatment period for those re-treated subjects 
with EN3835. 
The overall safety population is defined as all 
subjects who enter the open-label study 
period and received EN3835 in study 
EN3835-302 or EN3835-303. This 
population will include all Category I, II, and 
III subjects. All safety analyses will be based 
on this population. 
Section 4 
Synopsis, 
Statistical Methods: 
Day-180 
Observational 
Population 
Added 
Day-180 Observational Population:  
The Day-180 observational population will 
include all rollover subjects from studies 
EN3835-302/303. The safety analysis for the 
data obtained from Screening to Day 180 will 
be based on this population. 

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Section 4 
Synopsis, 
Statistical Methods: 
Time to Reduction-
in Response 
Population 
Durability Population: The durability 
population is defined as all subjects who 
have at least 1-level/2-level improvement in 
both CR-PCSS and PR-PCSS score/rating 
during the double-blind study for either/both 
treated buttocks. This population will 
include Category I and II subjects. The 
durability data will be collected up to 6 
months for Category I subjects and up to 5 
years for Category I and II subjects. 
Time to Reduction in Response Population: 
The time to reduction in response (TRR) 
population is defined as all subjects who 
have at least 1-level/2-level improvement in 
both CR-PCSS and PR-PCSS ratings during 
the double-blind study for either/both treated 
buttocks. This population will include 
Category I and II subjects. The TRR data will 
be collected up to 6 months for Category I 
subjects and up to 5 years for Category I and 
II subjects. 
Section 4 
Synopsis, 
ANALYSES: 
The analyses of cellulite assessments will be 
based on durability population. The 
durability of response will be defined from 
the time of assessing the efficacy (Day 71) to 
the loss of response study visit.  
The analyses of cellulite assessments will be 
based on the TRR population. The TRR will 
be defined from the time of assessing the 
efficacy (Day 71) in the double-blind study 
(EN3835-302/303) until the study visit in 
study EN3835-304 at which a composite 1-
level loss of response in both PR-PCSS and 
CR-PCSS is observed.  
The defined endpoints will include: 
The defined endpoints will include: 
• Proportion of subjects who lose their 
Reponses 
• Proportion of subjects with reduction of 
response 
- Proportion of subjects that both CR-PCSS 
and PR-PCSS scores/ratings are back to their 
baseline or worse 
- Proportion of subjects with both CR-PCSS 
and PR-PCSS ratings worsening 1-level 
compared to their corresponding score at Day 
71 in the double-blind study (EN3835-
302/303)  
 
- Proportion of subjects with both CR-PCSS 
and PR-PCSS ratings back to their baseline 
or worse 
- Proportion of subjects that both CR-PCSS 
and PR-PCSS scores/ratings are worsening 
2-levels comparing to their corresponding 
score at Day 71 in the double-blind studies 
(EN3835-302/303) 
- Proportion of subjects with both CR-PCSS 
and PR-PCSS ratings worsening 2-levels 
compared to their corresponding score at Day 
71 in the double-blind study (EN3835-
302/303) 
- Proportion of subjects that either CR-PCSS 
or PR-PCSS scores/ratings are worsening 
2-levels comparing to their corresponding 
score at Day 71 in the double-blind studies 
(EN3835-302/303) 
- Proportion of subjects with either CR-PCSS 
or PR-PCSS ratings worsening 2-levels 
compared to their corresponding score at Day 
71 in the double-blind study (EN3835-
302/303) 
 
- Proportion of subjects that both CR-PCSS 
and PR-PCSS scores/ratings are worsening 
1-level comparing to their corresponding 
score at Day 71 in the double-blind studies 
(EN3835-302/303) 
Moved to top of this bullet list 
• Changes in the PR-CIS total scores from 
baseline 
•Changes in the PR-CIS total scores from 
baseline 
 
•Proportion of subjects at each level of 
improvement in the S-GAIS 
•Proportion of subjects at each level of 
improvement in the subject self-rating scale 
•Proportion of subjects at each level of 
improvement in the SSRS 

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All results for each endpoint based on the 
collection time points as schedule at 
Section 5.1, Section 5.2, and Section 5.3 will 
be derived and be summarized by treated 
area , subject category, and study visit (day) 
using appropriate descriptive statistics. The 
baseline or reference data point will be 
detailed in the SAP. 
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). 
All results for each endpoint based on the 
collection time points will be derived and be 
summarized by treated area, treatment 
exposure category, and study visit (day) 
using descriptive statistics.  
In addition, local AEs associated with the 
injection site, including acute (eg, erythema, 
bruising, pain, nodules/mass, ulceration, 
blistering, pruritus, swelling, and/or 
induration) and/or chronic (eg, skin 
thickening, fibrosclerosis, peau d’orange 
changes) cutaneous adverse events will be 
recorded and evaluated for seriousness and 
severity. 
Section 4 
Synopsis, 
ANAYLSES: 
Immunogenicity 
Anti-AUX-I and anti-AUX-II antibody 
levels and a subset of neutralizing Anti-
AUX-I and anti-AUX-II antibody will be 
summarized using appropriate descriptive 
statistics. 
Anti-AUX-I and anti-AUX-II antibody levels 
and a subset of subjects’ samples anti-AUX-I 
and anti-AUX-II neutralizing antibodies will 
be summarized using descriptive statistics. 
Section 5.1 
Schedule of Events, 
Up to 180 Days 
Column crossing all rows stating 
(EN3835-302/303 Study Unblind) 
Deleted 
Column heading: Screening (≥Day 71 Visit 
of Double-blind Study)(±14 days) 
Column heading: Screening (≥Day 71 Visita 
of Double-blind Study)(±14 days) 
Column heading: Visit 1 Day 180 (±14 d) 
Column heading: Visit 1 Day 180b (±14 
days) M6 
Added 
Column: Durability Confirmation Visit l 
Digital Photography: X 
Review assessments’ training and use 
materials: X 
Patient Reported Photonumeric Cellulite 
Severity Scale (PR-PCSS): X f,g 
Review assessment’s training and use 
materials: X 
Clinician Reported Photonumeric Cellulite 
Severity Scale (CR-PCSS): X h 
Local Safety assessments: X k  
Adverse Events: Monitored throughout study 
Added 
Column: Unscheduled Clinic Visit c 
Digital Photography: X 
Prior/concomitant medications/procedures a: 
X 
Body weight: X 
Vital signs: X 
Clinical Laboratory: X 
Pregnancy testing b: X 
Unblinding of Investigator, subject and site 
to subjects’ treatments in EN3835-302/303: 
X i 
Assignment of Subject to Category I, II, or 
III: X j 

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Local Safety assessments: X k  
Adverse Events: Monitored throughout study 
Informed consent: Screening: X 
Informed consent m Screening: X; Day 180 
Visit: X 
Medical history including previous EFP 
treatments; and associated Visit X’s 
Deleted row 
Added row 
Review assessments’ training and use 
materials, Screening: X; Visit 1 Day 180: X 
Added row 
Subject Global Aesthetic Improvement 
(S-GAIS) , Screening: X d; Visit 1 Day 180: 
X d 
Subject Self Reporting Scale 
Subject Self-Rating Scale 
Added row 
Review assessment’s training and use 
materials, Screening: X; Visit 1 Day 180: X 
Added row 
Local Safety assessments: Screening: Xk;  
Visit 1 Day 180: X k; Unscheduled Clinic 
Visit: X k 
Adverse Events: X 
Adverse events: Monitored throughout study 
a 
Including Xiaflex 
d Including XIAFLEX as a possible 
concomitant medications; the use of the word 
‘prior’ refers to the period between the last 
visit from the previous Phase 3 clinical study 
through the signing of informed consent in 
the EN3835-304 study. 
b 
Serum pregnancy test occurs on 
Screening visit (carried over from 
Day 71/EOS visit of EN3835-302/303); 
Urine pregnancy test on Day 180 Visit 
e Serum pregnancy test occurs on Screening 
visit (carried over from Day 71/EOS visit of 
EN3835-302/303); urine pregnancy test on 
Day 180 Visit and, if deemed necessary, at an 
Unscheduled Visit.  
Added  
b Visit 1 Day 180 is in study EN3835-304; 
approximately 180 days after Day 71 of 
double-blind study. 
c 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). 
i Depending on the date of unblinding of 
subject’s treatment in EN3835-302/303; 
investigators, subjects, and site personnel 
may be unblinded at Day 180 Visit after 
assessments are completed or at a time 
thereafter during an unscheduled visit. If 
database lock occurs prior to Day 180, the 
investigator, subjects, and site personnel will 
remained blinded until Day 180 Visit 
assessments are completed. 
j Assignment of subjects to Categories will 
occur after unblinding of investigators, 
subject and site personnel to subjects’ 
treatment in EN3835-302/303 and will 

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depend on treatment and Day 71 cellulite 
severity improvements. Depending on the 
date of the database lock of the double-blind 
studies, assignments may occur at Day 180 
Visit after assessments are completed or at a 
time thereafter during an unscheduled visit. 
k Local adverse events associated with the 
injection site, including acute (eg, erythema, 
bruising, pain, nodules/mass, ulceration, 
blistering, pruritus, swelling, and/or 
induration) and/or chronic (eg, skin 
thickening, fibrosclerosis, peau d’orange 
changes) cutaneous adverse events, will be 
recorded and evaluated for seriousness and 
severity 
l  If the composite (CR-PCSS and 
PR-PCSS) ratings worsen by at least 1-level 
composite response ratings at Day 180 Visit 
for a subject that had a 2-level composite 
improvement at Day 71 of the double-blind 
study, an additional visit should be scheduled 
14 days (± 5 days) later to confirm reduction 
of response, via re-assessment with the 
CR-PCSS and PR-PCSS. 
m  Informed consent at Screening will 
address activities up through Day 180 Visit. 
Informed consent at Day 180 Visit will 
address the classification of subjects into 
Categories I, II, and III and activities and 
assessments that they will undergo. 
d=Days; EFP=Edematous fibrosclerotic 
panniculopathy; EOS=End of Study 
EFP=Edematous fibrosclerotic 
panniculopathy; EOS=End of Study; 
M=Month 
Section 5.2 
Schedule of Events, 
Eligible Category 
I/II Subjects – 
Treatment Session 
Assessments 
5.2 Category I Subjects 
5.2 Eligible Category I/II Subjects – 
Treatment Session Assessments 
Column headings:  
Procedures a ;Visit 2 Screen B Day 360 
(±7 d); Visit 3 Day 374 (±3 d); Visit 4 Day 
395 (±3 d); Visit 5 Day 416 (±3 d): Visit 6 
Day 444 (±5 d); Visit 7 Day 540 (±30 d); 
Visit 8 Day 720 (±30 d); Visit 9 Day 1080 
(±30 d), Visit 10 Day 1440 (±30 d); Visit 11 
Day 1800/EOS (±30 d) 
Column headings:  
Procedures a; Screening B b (Day -14 to -1 
relative to Tx Visit 1); Tx Visit 1 Tx 
Session 1 Day 1; Tx Visit 2 Tx Session 2; 
Day 22 (±3 days); Tx Visit 3 Tx Session 3 
Day 43 (±3 days); Tx Visit 4 End of 
Treatment/ Early Termination Day 71 
(+5 days) c; Unscheduled Clinic Visit a 
Added 
Column: Unscheduled Clinic Visit c 
Digital Photography: X 
Prior/concomitant medications/procedures a: 
X 
Body weight: X 
Vital signs: X 
Clinical Laboratory: X 
Pregnancy testing: X j 

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Injection site reactions/local tolerability in 
the buttocks p: X  
Adverse Events: Monitored throughout study 
Informed consent: Screening B b: X X q 
Informed consent: Screening B b: X q 
Medical history/EFP history including 
previous treatments: Screening B b: X 
Deleted row 
Height; Visit 6 Day 444: X 
Height; Screening B b: X 
Added row 
ECG; Screening B b: Xi 
Added row 
Review assessments’ training and use 
materials, Screening B b: X; Tx Visit 4 
Day 71: X 
Added row 
Subject Global Aesthetic Improvement 
(S-GAIS) l, Screening B b: X; Tx Visit 4 Day 
71: X  
Patient Reported Cellulite Impact Scale 
(PR-CIS)  
Subject Satisfaction With Cellulite 
Treatment Assessment  
Subject Self Reporting Scale (SSRS) 
Subject Global Aesthetic Improvement Scale 
(S-GAIS) l 
Patient Reported Cellulite Impact Scale 
(PR-CIS) l 
Subject Satisfaction With Cellulite Treatment 
Assessment l 
Subject Self-Rating Scale (SSRS) 
Added row 
Review assessment’s training and use 
materials, Screening B b: X; Tx Visit 4 
Day 71: X 
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). 
a During unscheduled visits, the 
Investigator or designee may perform any 
study procedure, except study drug 
administration, that they deem clinically 
necessary (eg, vital signs, clinical lab 
assessments, and and/or pregnancy test). 
Added 
b After the study drug treatment blind is 
broken in study EN3835-302/303 and 
subjects have been classified based on Day 
71 composite responses in study EN3835-
302/303, Category and Category II subjects 
that qualify for treatment may elect to receive 
one and only one course of EN3835 
retreatment (ie, 3 treatment sessions) in up to 
2 buttocks. 
 
c Upon completion of treatment, subject 
will be followed at intervals as in 
Section 5.3; if the 71-day treatment period 
overlaps with an Observation Visit in 
Section 5.3 for a subject, that particular 
Observation visit will be skipped and the 
subject will be assessed at the next scheduled 
Observation Visit in Section 5.3 
d Only includes the areas receiving 
retreatment 
Deleted 
e 
Including Xiaflex 
f Including XIAFLEX as a possible 
concomitant medication; the use of the word 

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‘prior’ refers to the period between the last 
visit from the previous Phase 3 clinical study 
through the signing of informed consent in 
the EN3835-304 study. 
h 
Urine pregnancy test 
j Serum pregnancy test on Screening visit 
and Day 71/EOS visit; urine pregnancy test 
on Day 1, Day 22, and Day 43 visits and 
Unscheduled Visit. 
l 
Each of the subject’s buttocks receiving 
retreatment must have scores/ratings of at 
least 2 in both the CR-PCSS and PR-PCSS. 
o Each buttock of Category I subjects are 
eligible to receive retreatment; at least one of 
Category II subject’s buttocks must have loss 
a 1-level composite rating in both CR-PCSS 
and PR-PCSS compared to double-blind 
study Day 71 ratings to be eligible to receive 
retreatment. 
Added 
p Local adverse events associated with the 
injection site, including acute (eg, erythema, 
bruising, pain, nodules/mass, ulceration, 
blistering, pruritus, swelling, and/or 
induration) and/or chronic (eg, skin 
thickening, fibrosclerosis, peau d’orange 
changes) cutaneous adverse events, will be 
recorded and evaluated for seriousness and 
severity.  
 
q  Informed consent for Category I and 
eligible Category II subjects who opt to 
receive retreatment. 
NOTE: Subjects who qualify for Category I 
status who choose NOT to receive additional 
retreatment will be considered Category III 
subjects. 
Deleted 
d=Days; EFP=Edematous fibrosclerotic 
panniculopathy; EOS=End of study 
ECG=Electrocardiogram; EFP=Edematous 
fibrosclerotic panniculopathy; EOS=End of 
study; Tx=Treatment 

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Section 5.3 
Schedule of Events, 
Category I/II 
Subjects –
Observation 
Assessments 
5.3 Category II Subjects 
5.3 Category I/II Subjects – Observation 
Assessments 
Column headings; Procedures; Visit 2 Day 
360 (±30 d); Visit 3 Day 540 (±30 d); Visit 4 
Day 720 (±30 d);  Visit 5 Day 900 (±30 d); 
Visit 6 Day 1080 (±30 d); Visit 7 Day 1260 
(±30 d); Visit 8 Day 1440 (±30 d); Visit 9 
Day 1620 (±30 d); Visit 10 Day 1800/EOS 
(±30 d) Durability Confirmation Visit a 
Column headings: Procedures; Visit 2 Day 
360 (±30 d) (M12); Visit 3 Day 540 (±30 d) 
(M18); Visit 4 Day 720 (±30 d) (M24); Visit 
5 Day 1080 (±30 d) (M36); Visit 6 Day 1440 
(±30 d) (M48); Visit 7 Day 1800/EOS (±30 
d) (M60); Durability Confirmation Visit a; 
Unscheduled Clinic Visit b 
Added 
Column: Unscheduled Clinic Visit b 
Digital Photography: X 
Prior/concomitant medications/procedures a: 
X 
Local safety assessments g: X  
Adverse Events: Monitored throughout study 
Informed consent: Visit 2: X 
Verification of informed consent: Visit 2: X 
Medical history/EFP history including 
previous treatments: Screening B b: X 
Deleted row 
Added row 
Review assessments’ training and use 
materials, Visits 2 – 7: X 
Added row 
Subject Global Aesthetic Improvement 
(S-GAIS) l,  Visits 2 – 7: X 
Patient Reported Cellulite Impact Scale 
(PR-CIS)  
Subject Satisfaction With Cellulite 
Treatment Assessment  
Subject Self Reporting Scale (SSRS) 
Subject Global Aesthetic Improvement Scale 
(S-GAIS) e 
Patient Reported Cellulite Impact Scale 
(PR-CIS) e 
Subject Satisfaction With Cellulite Treatment 
Assessment e 
Subject Self-Rating Scale (SSRS) 
Added row 
Review assessment’s training and use 
materials, Visits 2 – 7: X 
Local safety assessments g: all Visits: Xs 
a 
If the composite (CR-PCSS and 
PR-PCSS) score/rating for cellulite severity 
goes back to baseline values for a subject, an 
additional visit should be scheduled 14 days 
later to confirm durability, via re-assessment 
with CR-PCSS and PR-PCSS. If loss of 
response is confirmed, subjects will continue 
with annual visits only  
(ie, Days 720, 1080, 1440, and 1800).  
a If the composite (CR-PCSS and 
PR-PCSS) ratings worsen by at least 1 level 
composite response ratings for a subject, an 
additional visit should be scheduled 14 days 
later to confirm reduction of response, via re-
assessment with the CR-PCSS and PR-PCSS. 
If reduction of response is confirmed, 
subjects will be offered one course of 
retreatment (one and only one course of 
retreatment in up to 2 buttocks concurrently 
will be offered to an individual subject 
during this open-label study from Visit 1 to 
Visit 6 (approximately 6 to 48 months after 
Day 71 of the double-blind study, 
respectively) after which they will continue 
with observation visits only. 
b 
Photography and assessment should be 
limited to the regions that show a 2-level 
composite improvement (ie, if only one 
Deleted 

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buttock showed a 2-level composite 
response, only that buttock should be 
photographed. 
e 
Including Xiaflex 
c Including XIAFLEX as a concomitant 
medication; the use of the word ‘prior’ refers 
to the period between the last visit from the 
previous Phase 3 clinical study through the 
signing of informed consent in the EN3835-
304 study. 
Added 
b During unscheduled visits, the 
Investigator or designee may perform any 
study procedure that they deem clinically 
necessary (eg, vital signs and/or clinical lab 
assessments). 
f 
Before injection. 
Deleted 
h 
Urine pregnancy test 
Deleted 
j 
Assessment made via photographs (if 
treatment visit, use photographs taken before 
marking dimples and injection sites). 
e Assessment made via photographs.  
k Assessment of each re-treated buttock 
(independently if both buttocks received 
retreatment). 
f 
Assessment of each of the 2 buttocks is to 
be made independently. 
l 
Each of the subject’s buttocks receiving 
retreatment must have scores/ratings of at 
least 2 in both the CR-PCSS and PR-PCSS. 
NOTE: Subjects who qualify for Category I 
status who choose NOT to receive additional 
retreatment will be considered Category III 
subjects. 
Deleted 
Added 
g Local adverse events associated with the 
injection site, including acute (eg, erythema, 
bruising, pain, nodules/mass, ulceration, 
blistering, pruritus, swelling, and/or 
induration) and/or chronic (eg, skin 
thickening, fibrosclerosis, peau d’orange 
changes) cutaneous adverse events, will be 
recorded and evaluated for seriousness and 
severity. 
d=Days; EFP=Edematous fibrosclerotic 
panniculopathy; EOS=End of study 
d=Days; EFP=Edematous fibrosclerotic 
panniculopathy; EOS=End of study; 
M=Month(s) 
Section 5.4 
Schedule of Events, 
Category III 
Subjects - 
Assessments 
5.4 Category III Subjects 
5.4 Category III Subject Assessments 
Column headings: Procedures; Visit 2 Day 
360 (±30 d); Visit 3 Day 720 (±30 d); Visit 4 
Day 1080 (±30 d); Visit 5 Day 1440 (±30 d); 
Visit 6 Day 1800/EOS (±30 d)  
Procedures; Visit 2 Day 360 (±30 d) (M12); 
Visit 3 Day 540 (±30 d) (M18); Visit 4 Day 
720 (±30 d) (M24); Visit 5 Day 1080 (±30 d) 
(M36); Visit 6 Day 1440 (±30 d) (M48); 
Visit 7 Day 1800/EOS (±30 d) (M60) 
Added column 
Visit 3 Day 540 (±30 d) (M18): 
Prior/concomitant medications/procedures a: 
X 
Anti-AUX-I/anti-AUX-II antibody level: X 
Local safety assessments b: X 

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Adverse events: Monitored throughout study 
Added column 
Unscheduled Clinic Visit c  
Prior/concomitant medications/procedures a: 
X 
Local safety assessments b: X 
Adverse events: Monitored throughout study 
Informed consent: Visit 2: X 
Verification of informed consent: Visit 2: X 
Medical history including previous EFP 
treatments; Visit 2 Day 360: X; Visit 3 Day 
720:X; Visit 4 Day 1080: X; Visit 5 Day 
1440: X; Visit 6 Day 1800/EOS: X 
Deleted row 
Added spacer row 
Collection of samples: 
a 
Including Xiaflex 
a Including XIAFLEX as a concomitant 
medication; the use of the word ‘prior’ refers 
to the period between the last visit from the 
previous Phase 3 clinical study through the 
signing of informed consent in the EN3835-
304 study. 
Added 
b Local adverse events associated with the 
injection site, including acute (eg, erythema, 
bruising, pain, nodules/mass, ulceration, 
blistering, pruritus, swelling, and/or 
induration) and/or chronic (eg, skin 
thickening, fibrosclerosis, peau d’orange 
changes) cutaneous adverse events, will be 
recorded and evaluated for seriousness and 
severity 
c During unscheduled visits, the 
Investigator or designee may perform any 
study procedure that they deem clinically 
necessary. 
NOTE: Subjects who qualify for Category I 
status who choose NOT to receive additional 
retreatment will be considered Category III 
subjects 
Deleted 
d=Days; EFP=Edematous fibrosclerotic 
panniculopathy; EOS=End of study 
d=Days; EOS=End of study; M=Month 
Section 7  
List of 
Abbreviations 
Added 
TRR Time to reduction of response 
Section 9.2 
Secondary 
Objectives 
The secondary objective of this study is to 
assess the durability of response of EN3835 
in the treatment of edematous fibrosclerotic 
panniculopathy (EFP) in adult women. 
The secondary objective of this study is to 
assess the TRR to EN3835 in the treatment of 
edematous fibrosclerotic panniculopathy 
(EFP) in adult women. 

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Section 10.1 
Study Design 
This open-label extension study will be 
performed at multiple centers currently 
participating in the double-blind, 
placebo-controlled, parent trial 
(EN3835-302/ EN3835-303) in the United 
States. 
Following completion of safety and cellulite 
assessments at Day 71 of the double-blind 
study (EN3835-302/303), subjects will be 
asked to continue in the open-label extension 
to the double-blind study (ie, EN3835-304, 
the current study). Assessments made at 
Day 71/EOS of the double-blind study will 
serve as initial screening for the current 
open-label extension study. At the time of 
entry into the open-label study, subjects and 
Investigators will remain blinded to study 
drug. Until the EN3835-302/303 study drug 
blind is broken by the Sponsor, subjects will 
undergo observation-only visits at 6 months 
± 14 days, where both safety and cellulite 
severity assessments of the treated quadrant 
will be made. Upon completion and 
unblinding of the double-blind studies 
EN3835-302/303, subjects who received 
placebo during the double-blind studies will 
be discontinued, and subjects who received 
active EN3835 will be stratified into 
3 Categories: 
Category I: 1-level Composite Responders 
Category II: 2-Level Composite Responders 
Category III: Non-Composite Responders 
Category I subjects will be eligible for one 
additional retreatment course in up to two 
buttocks in the current open-label study, 
beginning on Day 360. Only buttocks with a 
composite 1-level improvement will be 
retreated. Assessment of open-label efficacy 
will be determined for up to 71 Days 
following retreatment, after which subjects 
will be observed annually for safety for up to 
5 years (Day 1800). Eligible subjects who 
qualify for Category I status who choose 
NOT to receive additional retreatment will 
operationally be treated as Category III 
subjects. 
Category II will include subjects who 
showed an improvement in cellulite severity 
of at least two levels in at least one buttock 
in both the PR-PCSS and the CR-PCSS 
(ie, 2-level composite responder) in 
EN3835-302 or EN3835-303. These subjects 
will be observed for continued durability of 
This open-label extension study will be 
performed at multiple centers currently 
participating in the double-blind, 
placebo-controlled, parent trials 
(EN3835-302/EN3835-303) in the United 
States. 
Following completion of safety and cellulite 
assessments (at least PR-PCSS and 
CR-PCSS) at Day 71 of the double-blind 
study (EN3835-302/303), subjects will be 
asked to continue in the open-label extension 
to the double-blind study (ie, EN3835-304, 
the current study). Assessments made at 
Day 71/EOS of the double-blind study will 
serve as initial screening for the current 
open-label extension study. At the time of 
entry into the open-label study and at Visit 1 
at Day 180 of study EN3835-304 
(approximately 6 months after Day 71 of 
study EN3835-302/302, subjects and 
Investigators and site personnel will remain 
blinded to study drug treatment received in 
the double-blind study. Even if the 
EN3835-302/303 study drug blind is broken 
by the Sponsor; subjects, Investigators and 
site personnel in study EN3835-304 will 
remain blinded until after Day 180 safety and 
cellulite severity assessments of each 
treatment area are completed. Upon 
completion and unblinding of the double-
blind studies EN3835-302/303 (which may 
occur immediately after Day 180 Visit 
assessments are completed if the study drug 
blind has been broken by Sponsor, or may 
occur during an visit (Unscheduled Visit) 
after Day 180 of the blind is not broken by 
Sponsor until sometime after Day 180), 
subjects who received placebo during the 
double-blind studies will be discontinued, 
and subjects who received active EN3835 
will be classified into one of 
three Categories:  
Category I: 1-Level Composite Responders 
Category II: 2-Level Composite Responders 
Category III: Non-Composite Responders 
Category I subjects will be eligible for one 
additional retreatment course in up to two 
buttocks in the current open-label study. 
Retreatment may begin on Day 180 if the 
study drug blind from the double-blind study 
(EN3835-302/303) has been broken. Only 
buttocks with a composite 1-level 
improvement or less will be retreated. 
Assessment of open-label efficacy following 

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response (defined below) approximately 
every 6 months, and will be observed for 
safety annually for up to 5 years (Day 1800). 
Category II subjects will not be eligible for 
retreatment. 
Category III subjects will include all other 
subjects who received active EN3835 in 
study EN3835-302 or EN3835-303 but did 
not meet criteria to be included in Category I 
or II (ie, non-composite responders). These 
subjects will be observed annually for safety 
for up to 5 years (Day 1800), and will not be 
eligible for retreatment during the study. 
The retreatment course for Category I 
subjects will consist of 3 treatment sessions 
separated by 21 days. Each retreatment 
session will consist of up to 12 injections 
(0.07 mg/0.3 mL per injection) of EN3835 
for a dose of 0.84 mg and volume of 3.6 mL 
(identical to the treatment course 
administered in the double-blind study), in 
each qualifying buttock (Table 3). Subjects 
will be assessed for safety on each day of 
injection during retreatment, and at 71 days 
after initiation of retreatment, and assessed 
for cellulite severity 22, 43, and 71 days 
following initiation of retreatment. 
For study purposes, durability of response is 
defined as the duration, until loss of 
response, of composite improvement in 
cellulite severity compared to the baseline 
level established during the double-blind 
study as assessed by both the PR-PCSS and 
the CR-PCSS until loss of response. Loss of 
response is defined as a composite 
worsening of cellulite severity back to 
baseline (for Category I), or of at least two 
levels (ie, worsening of 2 levels on both the 
PR-PCSS and CR-PCSS) for Category II. 
For open-label assessment of durability in 
Category II subjects, confirmation of loss of 
response will be established during a 
follow-up visit ~2 weeks after the loss of 
response is first detected. 
Once enrolled in the current open-label 
study, subjects will again receive 
instructions for use of the PR-PCSS and will 
subsequently use the scale to rate the 
severity of their cellulite in each of the 
treated areas on standardized computer 
monitors with the PR-PCSS instrument. 
Both the Investigator and the subject will 
remain blinded to each other’s assessments 
retreatment will be determined up to 
Treatment Visit 4 (Day 71 + 5 days), after 
which subjects will be observed, depending 
when during the 5 year period the subject 
receives retreatment, for every 6 months for 
2 years and then annually for up to 5 years 
(Day 1800) after Day 71 of study 
EN3835-302/303. Eligible subjects who 
qualify for Category I status who choose 
NOT to receive additional retreatment will 
have observation visits (Visits 2-7) as 
detailed in Section 5.3. 
Category II will include subjects who showed 
an improvement in cellulite severity of at 
least two levels in at least one buttock in both 
the PR-PCSS and the CR-PCSS (ie, 2-level 
composite responder) in EN3835-302 or 
EN3835-303. These subjects will be 
observed for TRR (defined below) and safety 
approximately every 6 months for 2 years 
and will be observed annually for up to 5 
years (Day 1800) from Day 71 of the double-
blind studies. Category II subjects who lose 
1-level composite response in at least one 
buttock relative to the composite 
improvement (at least one composite level) at 
Day 71 of the double-blind study will be 
eligible for retreatment as detailed in Section 
5.2; after which they will be observed at 
observation visits as detailed in Section 5.3. 
Category I and Category II subjects who in 
the observational phase of the study, will 
have cellulite assessments completed during 
the observational visits at Months 12, 18, 24, 
36, 48, and 60. At Months 12, 18, 24, 36, and 
48, if the ratings indicate that the buttock(s) 
is eligible for retreatments and the subject 
has not received EN3835 previously in study 
EN3835-304, the subject will be offered one 
course of treatment for the eligible 
buttock(s); one course of concurrent 
treatment for up to two eligible buttocks.  
Category III subjects will include all other 
subjects who received active EN3835 in 
study EN3835-302 or EN3835-303 but did 
not meet criteria to be included in Category I 
or II (ie, non-composite responders). These 
subjects will be observed for safety every 
6 months for 2 years and annually for up to 
5 years (Day 1800) as detailed in Section 5.4, 
and will not be eligible for retreatment during 
the study. 
The retreatment course for Category I 
subjects and for eligible Category II subjects 

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for the duration of the open-label study, even 
after the blind is broken for each double-
blind study by the Sponsor. 
The Schedule of Events for all subjects up 
through 180 days following studies 
EN3835-302/303 is provided in Section 5.1. 
Beyond Day 180, the Schedule of Events for 
Category I, II, and II subjects are provided in 
Section 5.2, Section 5.3, and Section 5.4, 
respectively.  
will consist of 3 treatment sessions separated 
by 21 days. Each retreatment session will 
consist of 12 injections (0.07 mg/0.3 mL per 
injection) of EN3835 for a dose of 0.84 mg 
and volume of 3.6 mL (identical to the 
treatment course administered in the 
double-blind study), in each qualifying 
buttock (Table 3) in up to two buttocks 
treated concurrently. One and only one 
retreatment course in up to 2 qualifying 
buttocks concurrently will be offered to 
Category I and eligible Category II subjects 
during this 5 year study. After initiation of 
retreatment (on Treatment Visit 1; Treatment 
Day 1), subjects will be assessed for safety 
on each day of injection during retreatment, 
and assessed for safety and cellulite severity 
on Treatment Visit 2 (Day 22), Treatment 
Visit 3 (Day 43) and Treatment Visit 4 
(Day 71). 
For study purposes; reduction of response 
(ie, lessening of response or loss of response) 
is defined as a 1-level composite worsening 
of cellulite severity improvement observed at 
Day 71 of the double-blind studies 
(EN3835-302/303) on both the PR-PCSS and 
CR-PCSS. TRR is defined as the time from 
assessing efficacy (Day 71 of double-blind 
study) to the study visit at which a composite 
1-level loss of response in both PR-PCSS and 
CR-PCSS is observed. Durability of response 
is defined as a complete loss of response in 
which cellulite severity returns back to 
baseline levels (on both the PR-PCSS and 
CR-PCSS on Day 1 of the double-blind 
studies). Confirmation of reduction of 
response and/or complete loss of response 
will be established during a follow-up visit 
~2 weeks after a composite reduction of 
response is first detected. 
Once enrolled in the current open-label 
study, subjects will again receive instructions 
for use of the PR-PCSS and will 
subsequently use the scale to rate the severity 
of their cellulite in each of the treatment 
areas on a standardized computer monitor 
with the PR-PCSS instrument. 
Both the Investigator and the subject will 
remain blinded to each other’s assessments 
for the duration of the open-label study, even 
after the study drug treatment blind is broken 
for each double-blind study by the Sponsor. 
Throughout the study, subjects and 
Investigators will be provided training 

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materials and will refresh on training prior to 
the use of each cellulite assessment at each 
visit. 
The Schedule of Events for all subjects up 
through 180 days following studies 
EN3835-302/303 is provided in Section 5.1. 
Beyond Day 180, the Schedule of Events for 
subjects classified as categories I and II and 
who are eligible and opt to receive 
retreatment is provided in Section 5.2 and in 
observational phase of study Section 5.3. The 
Schedule of Events for subjects in 
Category II who are not eligible for 
retreatment, or are in Category I and II and 
who are eligible but opt not to have 
retreatment, is provided in Section 5.3. The 
Schedule of Events for Category III subjects 
is shown in Section 5.4.  
Figure 1  
Study Design 
[Flow chart] 
[Revised flow chart] 
Table 3  
Study Retreatment (Category I Subjects 
Only) 
Dose (mg) at Each Treatment Visit 
0.84 mg per buttock × 2 buttocks = 1.68 mg 
(12 injections per buttock × 0.07 
mg/injection × up to 2 buttocks) 
Study Retreatment (Category I Subjects and 
Eligible Category II Subjects Only) 
Dose (mg) at Each Treatment Visit 
0.84 mg per buttock × up to 2 buttocks = 
1.68 mg (12 injections per buttock × 
0.07 mg/injection × up to 2 buttocks) 
Section 10.2 
Selection of Doses 
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 
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 (0.84 mg/buttock; total dose 
of 1.68 mg) supports the proposed dose to 
evaluate EN3835 in treatment of one or both 
buttocks. 
Section 10.3 
Study Drug 
Administration 
(Category I 
Subjects and 
Eligible Category II 
Subjects) 
Study Drug Administration (Category I 
Subjects) 
Study Drug Administration (Category I 
Subjects and Eligible Category II Subjects) 
Added 
Position B should be towards the head 
(cephalad) of the subject. 
Position C should be towards the feet 
(caudal) of the subject. 
In most cases, the plane containing injection 
points A, B, and C will be parallel to the long 
axis of the subject’s body. 
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 
NOTE: EN3835 is a foreign protein and 
Investigators must 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, 

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available with the Investigator and site staff 
must be familiar with their use. 
and the Investigator and site staff must be 
familiar with their use. 
Section 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 safety and 
durability of response of EN3835 0.84 mg 
per buttock in the concurrent treatment (total 
dose of up to 1.68 mg) of 2 bilateral buttocks 
with EFP in adult women. The study is being 
conducted as a multi-center, open-label 
extension study. 
Safety data and immunogenicity after repeat 
exposure (retreatment) and monitoring of 
previously EN3835 treated subjects for up to 
5 years (1800 days following Day 71 of 
double-blind), and Durability of the response 
to EN3835 (cellulite severity assessments) 
will be assessed at various time points. 
This study is a long-term follow-up study of 
subjects who received EN3835 0.84 mg per 
buttock in the concurrent treatment (total 
dose of up to 1.68 mg) of 2 bilateral buttocks 
with EFP in adult women in a 71-day 
double-blind, placebo-controlled study 
(EN3835-302 or EN3835-303). After 
completion in one of the aforementioned 
studies, subjects will be followed for up to 
5 years from the Day 71 of the double-blind 
study (EN3835-302/303), which is 
approximately 28 days after the last exposure 
of EN3835 in study EN3835-302/303. Study 
EN3835-304 is being conducted as a 
multi-center, open-label extension study. 
• Safety data, immunogenicity, and 
responsiveness after repeat exposure 
(retreatment) and monitoring of previously 
EN3835 treated subjects for up to 5 years 
(1800 days following Day 71 of double-
blind), 
• Safety data, immunogenicity and 
responsiveness after repeat exposure 
(retreatment) in subjects that show a 
reduction from the improvement observed at 
Day 71 of the double-blind studies and 
• Time to reduction in the response to 
EN3835 using cellulite severity assessments 
will be evaluated at various time points. 
Section 11.1.1  
All Subjects 
(Through Day 180) 
For the period prior to unblinding of 
EN3835-302/303, in order to be eligible to 
participate in the study, subjects must meet 
the following inclusion criteria:  
In order to be eligible to participate in the 
study, subjects must meet the following 
inclusion criteria:  
2. Have participated in and completed the 
double-blind Phase 3 study EN3835-302 or 
EN3835-303 
2. Have participated in and completed the 
double-blind Phase 3 study EN3835-302 or 
EN3835-303 (ie, assessed safety and 
obtained PR-PCSS and CR-PCSS ratings at 
Day 71/EOS of the double-blind study; does 
not include early termination subjects). 
4. Be judged to be in good health, based 
upon the results of a medical history, 
physical examination, and laboratory profile 
at Screening 
4. Be judged to be in good health, based 
upon the results of a physical examination, 
and laboratory profile at Screening 
NOTE: After unblinding of EN3835-302/ 
303, subjects who received active EN3835 
will be placed into one of 3 categories based 
on their responder status (Section 10.1). For 
each category, the following Inclusion 
Criteria apply beyond Day 180. 
NOTE: After Day 180 Visit assessments are 
completed in study EN3835-304 and 
unblinding of EN3835-302/303, subjects who 
received EN3835 in EN3835-302 or 
EN3835-303 will be placed into one of three 
categories based on their responder status of 
each of their buttocks at Day 71 in study 
EN3835-302 or EN3835-303 (Section 10.1). 

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Investigators, subjects and all site personnel 
will be blinded to the treatment that the 
subjects received in the double-blind studies 
until assessments at the Day 180 visit of 
study EN3835-304 are completed; even if 
this visit occurs after the EN3835-302/303 
studies are unblinded by Endo. Investigator, 
subjects and site personnel will be unblinded 
on Day 180 of study EN3835-304 after 
Day 180 assessments are completed or at an 
Unscheduled Visit, pending when database 
lock and unblinding of studies EN3835-302/ 
303 occurs relative to Day 180 of this current 
study EN3835-304. For each category, the 
following Inclusion and Exclusion Criteria 
apply beyond the day that the investigator, 
subject, and site personnel are unblinded: 
Section 11.1.2 
Category I Subjects 
(Post Unblinding of 
EN3835-302/303) 
3. At least one buttock having: 
a. a score of ≥2 (mild) as reported by the 
subject (PR-PCSS), and 
b. a score of ≥2 (mild) as reported by the 
Investigator (CR-PCSS) 
Deleted 
4. Be willing to apply sunscreen to the 
buttocks before each exposure to the sun 
while participating in the retreatment portion 
of the study (ie, Visit 2 through Visit 6) 
3. Be willing to apply sunscreen to the 
buttocks before each exposure to the sun 
while participating in the retreatment portion 
of the study (ie, Treatment Visit 1 through 
Treatment Visit 4) 
5. Be judged to be in good health, based 
upon the results of a medical history, 
physical examination, and laboratory profile 
at Screening 
4. Be judged to be in good health, based 
upon the results of a physical examination, 
and laboratory profile at Screening 
Section 11.1.3 
Category II 
Subjects (Post 
Unblinding of 
EN3835-302/303) 
2. Maximum composite response in either 
or both buttocks in double-blind study 
EN3835 302 or EN3835-303 was at least a 
2-level composite improvement on CR 
PCSS/PR PCSS 
2. Maximum composite response at Day 71 
in either or both buttocks in double-blind 
study EN3835-302 or EN3835-303 was at 
least a 2-level composite improvement on 
CR-PCSS/PR-PCSS 
Section 11.1.5 
Retreatment 
Subjects (Eligible 
Subjects Whom opt 
to Receive 
Retreatment) 
Added 
1. Voluntarily sign and date an informed 
consent agreement  
2. Subjects who opt for retreatment must 
meet one of the following criterion: 
a. All criteria for Category I subjects; OR 
b. All criteria for Category II subjects, AND 
must have at least one buttock that at Day 71 
in double-blind study EN3835-302 or 
EN3835-303 was at least a 2-level composite 
improvement on CR-PCSS/ PR-PCSS that at 
a subsequent visit showed at least a 1-level 
composite reduction of response (ie, a 
reduction in severity by 1-level in both the 
PR-PCSS and CR-PCSS) compared to the 
Day 71 ratings in double-blind study 
EN3835-302/303 in that buttock(s). 

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Section 11.2.1  
All Subjects 
(Through Day 180) 
For the period prior to unblinding of 
EN3835-302/303, in order to be eligible to 
participate in the study, subjects must meet 
the following exclusion criteria: 
A subject will be excluded from study 
participation if she: 
For the period from completing Day 71 of the 
double-blind study (EN3835-302 or 
EN3835-303) through Day 180 (Visit 1) of 
study EN3835-304, in order to be eligible to 
participate in the study, subjects must meet 
the following exclusion criteria: 
A subject will be excluded from study 
participation if she: 
1. Intends to or has used any of the 
following for the treatment of EFP on a 
buttock at any time during the course of the 
study, including (but not limited to): 
1. Intends to or has used any of the 
following for the treatment of EFP on a 
buttock at any time during the time period 
from Day 71 of double-blind study EN3835-
302 or EN3835-303 through Day 180 Visit in 
study EN3835-304 (approximately 6 months 
after Day 71 of study EN3835-302 or 
EN3835-303, including (but not limited to): 
a. Liposuction in a buttock during the 
12-month period before injection of study 
drug 
a. Liposuction in a buttock 
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 
b. Injections (eg, mesotherapy); 
radiofrequency device treatments; laser 
treatment; buttock implant treatment; 
cryolipolysis; or surgery (including subcision 
and/or powered subcision) within a buttock 
c. Any investigational treatment for EFP on 
a buttock during the 12 month period before 
injection of study drug 
c. Any investigational treatment for EFP on 
a buttock, other than the treatment received 
in study EN3835-302/303  
d. Endermologie™ or similar treatments 
within a buttock during the 6-month period 
before injection of study drug 
d. Endermologie™ or similar treatments 
within a buttock  
e. Massage therapy within a buttock during 
the 3-month period before injection of study 
drug 
e. Massage therapy within a buttock and/or 
home therapies to prevent or mitigate EFP 
within a buttock 
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 
f. Creams (eg, Celluvera™, TriLastin®) 
2. Intends to use tanning spray or tanning 
booths during the study 
2. Intends to use tanning spray or tanning 
booths during this period 
3. Has received an investigational drug or 
treatment within 30 days before injection of 
study drug 
 
3. Has received or intends to receive an 
investigational drug or treatment, other than 
the treatment received in study EN3835-
302/303 during this period 
4. Any other condition(s) that, in the 
Investigator’s opinion, might indicate the 
subject to be unsuitable for the study 
4. Any other condition(s) that, in the 
Investigator’s opinion, might indicate the 
subject to be unsuitable for the study 
NOTE: After unblinding of EN3835-302/ 
303, subjects who received active EN3835 
will be placed into one of 3 categories based 
on their responder status (Section 10.1). For 
NOTE: After Day 180 Visit assessments are 
completed in study EN3835-304 and 
unblinding of EN3835-302/303, subjects who 
received EN3835 in EN3835-302 or 

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each category, the following Exclusion 
Criteria apply beyond Day 180. 
EN3835-303 will be placed into one of three 
categories based on their responder status of 
each of their buttocks at Day 71 in study 
EN3835-302 or EN3835-303 (Section 10.1). 
Investigators, subjects and all site personnel 
will be blinded to the treatment that the 
subjects received in the double-blind studies 
until assessments at the Day 180 visit of 
study EN3835-304 are completed; even if 
this visit occurs after the EN3835-302/303 
studies are unblinded by Endo. Investigator, 
subjects and site personnel will be unblinded 
on Day 180 of study EN3835-304 after 
Day 180 assessments are completed or at an 
Unscheduled Visit, pending when database 
lock and unblinding of studies EN3835-302/ 
303 occurs relative to Day 180 of this current 
study EN3835-304. For each category, the 
following Inclusion and Exclusion Criteria 
apply beyond the day that the investigator, 
subject, and site personnel are unblinded: 
Section 11.2.2 
Category I Subjects 
(Post Unblinding of 
EN3835-302/303) 
Added 
Exclusion Criteria for Subjects Whom opt for 
Observations Only (ie, no retreatment): None 
A Category I subject will not receive 
additional treatments and will be moved to 
Category III status if she: 
1. Is unwilling to receive one additional 
course of open-label retreatment (3 treatment 
visits) for EFP with EN3385 
2. 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 
3. Has any of the following local conditions 
in the areas to be treated: 
a. History of lower extremity thrombosis or 
post-thrombosis syndrome 
Deleted 

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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. Requires the following concomitant 
medications before or during participation in 
retreatment portion 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 
5. 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, including (but not 
limited to): 
a. Liposuction in a buttock since completion 
of the double-blind study 
b. Injections (eg, mesotherapy); 
radiofrequency device treatments; laser 
treatment; buttock implant treatment; 
cryolipolysis; or surgery (including 
subcision and/or powered subcision) within a 
buttock since completion of the double-blind 
study. 
c. Any investigational treatment for EFP on 
a buttock since completion of the 
double-blind study 
d. Endermologie™ or similar treatments 
within a buttock since completion of the 
double-blind study 
e. Massage therapy within a buttock during 
the 3-month period before retreatment with 
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 retreatment with study drug 
6. Prior to and during the course of 
retreatment (Visit 2 through Visit 6), is 
presently nursing or providing breast milk 
7. Prior to and during the course of 
retreatment (Visit 2 through Visit 6), intends 
to become pregnant during the study 
8. Prior to and during the course of 
retreatment (Visit 2 through Visit 6), intends 

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to use tanning spray or tanning booths during 
the study 
9. Has received an investigational drug or 
treatment within 30 days before retreatment 
with study drug 
10. Has a known systemic allergy to 
collagenase or any other excipient of study 
drug 
11. Has received any collagenase treatments 
at any time since completion of the double-
blind study 
12. Any other condition(s) that, in the 
Investigator’s opinion, might indicate the 
subject to be unsuitable for Category I 
retreatment. 
Section 11.2.3 
Category II 
Subjects (Post 
Unblinding of 
EN3835-302/303) 
Added 
Exclusion Criteria for Subjects Whom opt for 
Observation Only (ie, no retreatment): 
1. Intends to or has used any of the 
following for the treatment of EFP on a 
buttock at any time during the course of the 
study, including (but not limited to): 
1. Intends to or has used any of the 
following for the treatment of EFP on a 
buttock at any time during the course of the 
study: 
a. Liposuction in a buttock during the 
12-month period before injection of study 
drug 
a. Liposuction in a buttock 
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 
b. Injections (eg, mesotherapy); 
radiofrequency device treatments; laser 
treatment; buttock implant treatment; 
cryolipolysis; or surgery (including subcision 
and/or powered subcision) within a buttock 
c. Any investigational treatment for EFP on 
a buttock during the 12-month period before 
injection of study drug 
c. Any investigational drug or treatment for 
EFP on a buttock (other than treatment in 
study EN3835-302/303) 
d. Endermologie™ or similar treatments 
within a buttock during the 6-month period 
before injection of study drug 
d. Endermologie™ or similar treatments 
within a buttock 
e. Massage therapy within a buttock during 
the 3-month period before injection of study 
drug 
e. Massage therapy within a buttock during 
the 3-month period before observational visit 
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 
f. Creams (eg, Celluvera™, TriLastin®) 
and/or home therapies to prevent or mitigate 
EFP within a buttock during the 2-week 
period before observational visit 
2. Has received an investigational drug or 
treatment within 30 days before injection of 
study drug 
2. Has received an investigational drug or 
treatment (other than treatment in study 
EN3835-302/303) 
3. Any other condition(s) that, in the 
Investigator’s opinion, might indicate the 
subject to be unsuitable for the study 
3. Any other condition(s) that, in the 
Investigator’s opinion, might indicate the 
subject to be unsuitable for the study 

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Section 11.2.5 
Retreatment 
Subjects (Eligible 
Subjects Whom opt 
to Receive 
Retreatment) 
Added 
Exclusion Criteria for Subjects Whom opt to 
Receive Retreatment: 
1. Has any of the following systemic 
conditions: 
a. Coagulation disorder 
b. Evidence or history of malignancy (other 
than excised basal-cell or squamous-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 
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 
retreatment portion the trial: 
a. Anticoagulant or antiplatelet medication 
or has received anticoagulant or antiplatelet 
medication (except for ≤150 mg aspirin 
daily) within 7 days before or 7 days after 
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 since completion 
of the double-blind study 
b. Injections (eg, mesotherapy); 
radiofrequency device treatments; laser 
treatment; buttock implant treatment; 

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cryolipolysis; or surgery (including subcision 
and/or powered subcision) within a buttock 
since completion of the double-blind study 
c. Any investigational treatment for EFP on 
a buttock since completion of the 
double-blind study 
d. Endermologie™ or similar treatments 
within a buttock since completion of the 
double-blind study 
e. Massage therapy within a buttock during 
the 3-month period before retreatment with 
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 retreatment with study drug 
5. Prior to and during the course of 
retreatment (Treatment Visit 1 through 
Treatment Visit 4), is nursing or providing 
breast milk 
6. Prior to and during the course of 
retreatment (Treatment Visit 1 through 
Treatment Visit 4), intends to become 
pregnant during the study 
7. Prior to and during the course of 
retreatment (Treatment Visit 1 through 
Treatment Visit 4), intends to use tanning 
spray or tanning booths during the study 
8. Has received an investigational drug or 
treatment, other than treatment in study 
EN3835-302/303, within 30 days before 
retreatment with study drug 
 
 
9. Has a known systemic allergy to 
collagenase or any other excipient of study 
drug 
10. Has received any collagenase treatments 
at any time since completion of the double-
blind study 
11. Any other condition(s) that, in the 
Investigator’s opinion, might indicate the 
subject to be unsuitable for retreatment 
Section 12.1  
Study Visits 
The Schedule of Events to be performed at 
each visit prior to unblinding of studies 
EN3835-302/303 is shown in Section 5.1. 
Following completion and unblinding of 
EN3835-302/303, subjects will be placed 
into one of 3 categories based on their 
treatment and responder status (Section 
10.1), and the Schedule of Events for subject 
categories I, II, and III are shown in Section 
5.2, Section 5.3, and Section 5.4, 
respectively. 
The Schedule of Events for all subjects up 
through 180 days following studies 
EN3835-302/303 is provided in Section 5.1. 
Beyond Day 180, the Schedule of Events for 
subjects classified as categories I and II and 
who are eligible and opt to receive 
retreatment is provided in Section 5.2 and in 
observational phase of study Section 5.3. The 
Schedule of Events for subjects in 
Category II who are not eligible for 
retreatment, or are in Category I and II and 
who are eligible but opt not to have 

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retreatment, is provided in Section 5.3. The 
Schedule of Events for Category III subjects 
is shown in Section 5.4. 
Section 12.1.2 
Subject Screening 
Added  
If the Screening Visit for a subject is within 
14 days of the subject’s Day 71 of study 
EN3835-302/303, the Screening Visit 
assessments for a subject will be 
pre-populated by a data transfer of the results 
of assessment of Day 71 (and height and 
Fitzpatrick scale rating of Day 1) of study 
EN3835-302/303 for that subject. 
If the Screening Visit for a subject is greater 
than 14 days of the subject’s Day 71 of study 
EN3835-302/303, the Screening Visit 
assessments will be performed as detailed in 
Section 5.1 with only the subject ID and 
Fitzpatrick scale rating transferring from 
Day 1 of study EN3835-302/303 and 
pre-populating the EDC of study 
EN3835-304. All medical history occurring 
between completion of study 
EN3835-302/303 and the Screening Visit of 
study EN3835-304 will be considered 
adverse events and 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). 
Section 12.1.3 
Medical History 
During the screening period, the Day 360 
Visit, and at all Visits at or beyond Day 540, 
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). 
Since this is a long-term rollover study for 
subjects that participated and completed the 
double-blind study (EN3835-302 or 
EN3835-303), in which the subjects’ medical 
history was collected; there will be no 
medical history collected for study 
EN3835-304. 
Section 12.1.5  
Day 180 Visit 
Subjects will return at 180 days (±14 days) 
following initial injection of EN3835 in one 
of the double-blind studies for cellulite 
severity evaluation visits of the open-label 
study. Assessments to be completed at these 
visits are detailed in Section 5.1. Following 
unblinding of EN3835-302/303, subjects 
who received placebo will be discontinued, 
and subjects who received active EN3835 
will be classified into 3 categories based on 
responder status. 
Subjects will return at 180 days (±14 days) 
following their Screening Visit (Day 71 of 
the double-blind studies (EN3835-302 or 
EN3835-303)) for cellulite severity 
assessments. All assessments will be 
completed as detailed in Section 5.1 prior to 
unblinding of the subject’s treatment 
assignment in the double-blind study. Local 
safety assessments (Section 14.6.1) and 
adverse events will be monitored 
(Section 14). 
If unblinding of drug treatment in EN3835 
302/303 occurs by the Sponsor prior to a 
subject’s Day 180 visit, Investigators, 
subjects and site personnel will remain 
blinded to the subject’s drug treatment in the 
double-blind studies until after the Day 180 

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assessment have been completed. After 
assessments are completed, unblinding will 
occur at the site and subjects who received 
placebo will be discontinued, and subjects 
who received active EN3835 will be 
classified into one of three categories based 
on responder status of each of their buttocks 
in the double-blind study (Section 10.1). If 
the subject is classified to a classification and 
has ratings that qualify for retreatment (ie, all 
Category I subjects will be offered 
retreatment; Category II subjects that have 
lost 1-composite level of response (ie, at least 
a 1-level worsening of both PR-PCSS and 
CR-PCSS in at least one buttock). If there is 
a composite worsening of cellulite severity of 
1-level (ie, worsening of both the PR-PCSS 
and CR-PCSS by at least 1 severity levels) 
detected in a Category II subject, the 
confirmation of loss of response will be 
established during a follow-up visit ~2 weeks 
after the loss of response is detected at 
Day 180 as described in Section 12.2.2.3 
(Confirmation Visit). If a Category I subject 
accepts the offer of retreatment at the 
Day 180 visit, Screening B of the Treatment  
Phase of the protocol may occur on the same 
day as the Day 180 Visit. If the loss of 
response in a Category II subject is 
confirmed and the subject accepts the offer of 
retreatment at the Confirmation Visit, 
Screening B of the Treatment Phase may 
occur on the same day as the Confirmation 
Visit. If the loss of response is not confirmed, 
the subject will be considered to not have lost 
response and will not be offered retreatment. 
If the unblinding has not occurred by a 
subject’s Day 180 visit, an Unscheduled Visit 
will be arranged after unblinding has 
occurred (see Section 12.4) and the subjects 
will be classified at this Unscheduled Visit 
or, if received placebo, will be discontinued. 
If a Category I subject decides to accept the 
offer of retreatment, the subject may be 
screened (Screening B Visit of the Treatment 
Phase) during the Unscheduled Visit. If there 
is a composite worsening of cellulite severity 
of 1-level (ie, worsening of both the 
PR-PCSS and CR-PCSS by at least 1 severity 
levels) detected in a Category II subject 
during the Unscheduled Visit, the 
confirmation of loss of response will be 
established during a follow-up visit ~2 weeks 
after the loss of response is detected as 

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described in Section 12.2.2.3 (Confirmation 
Visit). If the loss of response in a Category II 
subject is confirmed and the subject accepts 
the offer of retreatment at the Confirmation 
Visit, Screening B of the Treatment Phase 
may occur on the same day as the 
Confirmation Visit. If the loss of response is 
not confirmed, the subject will be considered 
to not have lost response and will not be 
offered retreatment.  
As stated in Section 10.1, either on Day 180 
Visit after assessments have been completed 
or at an Unscheduled Visit, once the study 
blind is broken, the EN3835-302/303 placebo 
subjects will be discontinued, and subjects 
who received active EN3835 in their 
respective double-blind study will be 
classified into one of three categories based 
on their response in the double-blind study. 
Section 12.2  
Study Visits (Post 
Unblinding of 
EN3835-302/ 303) 
Once the study blind is broken, the 
EN3835-302/303 placebo subjects will be 
discontinued, and subjects who received 
active EN3835 in their respective double-
blind study will be classified into one of 
three categories (Section 10.1), based on 
their response in the double-blind study. 
Deleted 
Section 12.2 
Category I Subjects 
and Category II 
Subjects Visits 
(Post Unblinding of 
EN3835-302/ 303 
Assessments to be completed at these visits 
are detailed in Section 5.2. Subjects are to 
return for a course of retreatment one year 
after the Day 71 Visit of the double-blind 
study, and will be assessed at regular 
intervals thereafter for cellulite severity and 
safety until they have completed 
approximately 5 years (1800 days) from 
Day 71 of the double-blind study. At these 
visits, the region previously treated with 
EN3835 in the double-blind EN3835-302/ 
303 study will be evaluated (Section 5.2). 
The duration of response for composite 
1-level responders (ie, Category I) will also 
be assessed at 180 days after the Day 71 
Visit of the double-blind study. Loss of 
response is defined as a composite 
worsening of cellulite severity back to 
baseline levels (on both the PR-PCSS and 
CR-PCSS). 
Assessments to be completed at these visits 
are detailed in Section 5.2 (Treatment 
Assessments) and in Section 5.3 
(Observation Assessments). 
Added 
Beginning at Day 180 (ie, approximately 
6 months after Day 71 Visit of the 
double-blind study); after Day 180 
assessments have been completed in a 
blinded fashion, all Category I subjects will 
be offered a course of retreatment. Category 
II subjects who have shown a 1-level 
composite reduction of response compared to 

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their Day 71 from EN3835-302/302 
improvement will be offered a course of 
retreatment; and assessments to be completed 
at these Treatment Assessments are detailed 
in Section 5.2. After completing Day 71 of 
the retreatment in this open-label study, the 
subjects will be assessed at intervals for 
cellulite severity and safety as detailed in 
Section 5.3 until they have completed 
approximately 5 years (1800 days) from 
Day 71 of the double-blind study. Category II 
subjects that have not shown a 1-level 
composite reduction (ie, have maintained a 
successful response), and/or Category I 
and/or Category II subjects who are eligible 
for a retreatment course but opt not to receive 
retreatment will be assessed at intervals 
(Section 5.3) for cellulite severity and safety 
until they have completed approximately 
5 years from Day 71 of the double-blind 
study. If the subject’s buttocks become 
eligible for retreatment based on the ratings 
of an observational visit and if they have not 
already received a course of retreatment, they 
will be offered retreatment up to including 
Observational Visit 6 (Month 48); no 
retreatments will be offered after Visit 6. The 
TRR for composite 1-level responders(ie, 
Category I) will also be assessed at 180 days 
after the Day 71 Visit of the double-blind 
study as well as after Treatment Visit 4 
(Retreatment Day 71) of this open-label 
study for those buttocks that are retreated. 
Buttocks not retreated will be assessed at 
each of the observation visits as shown in 
Section 5.3. TRR is defined as a 1-level 
composite worsening of cellulite severity 
levels (on both the PR-PCSS and CR-PCSS). 
If a treatment period eclipses (or overlaps) a 
scheduled observational visit, the 
observational visit will be skipped and the 
subject will re-enter the observational 
schedule at the next interval visit. For 
example, if a subject initiated retreatment on 
Day 351 (which would then be Treatment 
Visit 1), the treatment period would proceed 
for approximately 71 days until Day 421 
(Treatment Visit 4) and the Observational 
Visit at Day 360 would be skipped; the 
subject’s next observational visit would be 
Day 540. 
Treatments will not be offered to any subject 
after Visit 6 (Day 1440 ±30 days; Month 48 
± 1 month). 

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Section 12.2.1 
Treatment 
Assessments 
(Treatment is 
Optional for 
Eligible Subjects) 
12.2.1.1. Visit 2 (Screening B) 
12.2.1.1. Screening B (Days -14 to -1 
Relative to Treatment Visit 1) 
The following procedures will be performed 
and documented during Visit 2: 
The following procedures will be performed 
and documented during Screening B: 
4. Subjects will get instruction on the use of 
the PR-PCSS (Section 13.1.2.1) 
4. Subjects will get instruction on the use of 
the PR-PCSS (Section 13.1.2.1) and review 
training and use materials. 
6. Patient Reported Cellulite Impact Scale 
(PR-CIS) assessment (Section 13.1.2.2); note 
this assessment is of both left and right 
buttocks rather than each individual buttock 
6. Subjects will review subject cellulite 
assessment training and use materials prior to 
use of the S-GAIS, PR-CIS, Subject 
Satisfaction with Cellulite Treatment 
Assessment, and the SSRS. 
9. 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 eligibility of the 
buttocks for retreatment (to be eligible, a 
buttock must have a composite score of at 
least 2 on the PR-PCSS and CR-PCSS). 
7. Subject Global Aesthetic Improvement 
Scale (S-GAIS) (Section 13.1.2.2); subjects 
will rate each of their two buttocks while 
viewing pretreatment images from Day 1 of 
the double-blind study (EN3835-302/303) 
10. Medical history including EFP history 
(Section 12.1.3) 
8. 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 
12. Physical examination including 
measurement of body weight (Section 14.11) 
11. After the subject has completed the 
PR-PCSS ratings and after the Investigator 
has reviewed the training and use material for 
the CR-PCSS, 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 eligibility of the buttocks for 
retreatment 
13. Physical examination including 
measurement of body weight and height 
(Section 14.11) 
Section 12.2.1.1 
Screening B (Days 
-14 to -1 Relative 
to Treatment 
Visit 1) 
Added 
15. 12-lead ECG (Section 14.10) 
17. Injection site reactions/local tolerability 
in the buttocks (Section 14.6.1) 
Section 12.2.1.2 
Selecting and 
Marking Dimples 
during Treatment 
Visits 
Category I subjects eligible for retreatment 
can receive up to 3 retreatment visits of 
study drug as outlined in Section 5.2 unless 
the buttock is dimple-free (score of 0 on 
CR-PCSS as reported by the Investigator) at 
Visit 4 (Day 395) and/or Visit 5 (Day 416). 
Category I subjects and Category II subjects 
eligible for retreatment can receive up to 
3 retreatment visits of study drug as outlined 
in Section 5.2 unless the buttock is 
dimple-free (score of 0 on CR-PCSS as 

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reported by the Investigator) at Treatment 
Visit 2 and/or Treatment Visit 3. 
 
If no injections in a particular buttock (right 
or left) are given at Visit 4, subjects will still 
be assessed for retreatment in the 
contralateral buttock at Visit 4 if the buttock 
was retreated at Visit 3, and when they 
return for Visit 5, 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 Visit 5 should be given. 
If no injections in a particular buttock (right 
or left) are given at Treatment Visit 2, 
subjects will still be assessed for retreatment 
in the contralateral buttock at Treatment Visit 
2 if the buttock was retreated at Treatment 
Visit 1, and when they return for Treatment 
Visit 3, 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. 
Section 12.2.1.3 
Digital 
Photography during 
Treatment Visits 1, 
2, and 3 
12.2.1.3. Digital Photography during Visits 
3, 4, 5 
During each retreatment visit, each of the 
eligible buttocks to be retreated 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. 
In addition, a buttock that is not retreated 
will be photographed and monitored. 
12.2.1.3. Digital Photography during 
Treatment Visits 1, 2, and 3 
During each retreatment visit, each of the 
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. 
Section 12.2.1.4.1 
Treatment Visit 1: 
Pre-Injection 
12.2.1.4. Visit 3 (Day 374) 
12.2.1.4. Treatment Visit 1 
12.2.1.4.1. Visit 3: Pre-Injection 
12.2.1.4.1. Treatment Visit 1: Pre-Injection 
For each subject, the areas eligible for 
retreatment will be determined via IWRS 
based on the PR-PCSS/CR-PCSS scores 
obtained during Visit 2. Both buttocks will 
be photographed during the retreatment 
visits. 
For each subject, the areas eligible for 
retreatment will be confirmed via the IWRS 
based on the PR-PCSS/CR-PCSS ratings 
obtained during Treatment Visit 1. Each 
buttock will be photographed during the 
retreatment visits. 
2. Subjects will get instruction on the use of 
the PR-PCSS (Patient Instructions for Use of 
PR-PCSS) 
2. Subjects will get instruction on the use of 
the PR-PCSS (Patient Instructions for Use of 
PR PCSS) and review training and use 
materials 
Added 
4.The Investigator will review training and 
materials for the use of the CR-PCSS 
Section 12.2.1.4.2 
Treatment Visit 1: 
Injection and Post-
injection 
12.2.1.4.2. Visit 3: Injection and 
Post-injection 
12.2.1.4.2. Treatment Visit 1: Injection and 
Post-injection 
Section 12.2.1.5.1 
Treatment Visits 2 
and 3: Pre-injection 
12.2.1.5. Visits 4 and 5 (Day 395 and 
Day 416)  
12.2.1.5. Treatment Visits 2 and 3 (Day 22 ± 
3 days and Day 43 ± 3 days) 
12.2.1.5.1. Visits 4 and 5: Pre-injection 
12.2.1.5.1. Treatment Visits 2 and 3: 
Pre-injection 
6. Subject Cellulite Assessments of each of 
the buttocks receiving retreatment using the 
photographic image of each buttock before 
marking dimples and injection sites 
6. Subject Cellulite Assessments, after 
review of training and use materials, of each 
of the buttocks using the photographic image 
of each buttock before marking dimples and 
injection sites 

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7. Investigator Cellulite Assessments live of 
each of the buttocks receiving retreatment 
prior to marking dimples and injection sites 
using: 
7. Investigator Cellulite Assessments 
conducted, after review of training and use 
material, of each of the buttocks receiving 
retreatment prior to marking dimples and 
injection sites using 
Section 12.2.1.6 
Treatment Visit 4 
(Day 71+ 5 days) 
12.2.1.6. Visit 6 (Day 444) 
12.2.1.6. Treatment Visit 4 (Day 71+ 5 days) 
The following procedures will be performed 
at Visit 6: 
The following procedures will be performed 
at Visit 4: 
2. Measurement of body weight and height 
2. Measurement of body weight 
Added 
6. Subject will review training and use 
materials for the PR-PCSS, S-GAIS, PR-CIS, 
Subject Satisfaction with Cellulite Treatment 
Assessment, and SSRS 
b. Patient Reported Cellulite Impact Scale 
(PR-CIS) assessment (Section 13.1.2.2); note 
this assessment is of both left and right 
buttocks rather than each individual buttock. 
b. Subject Global Aesthetic Improvement 
Scale (S-GAIS) (Section 13.1.2.2); subjects 
will rate each of their two buttocks while 
viewing pretreatment images from Day 1 of 
the double-blind study (EN3835-302/303) 
7. Subject will complete the 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. 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 
while viewing images from Treatment Visit 4 
(Day 71) of EN3835-304.  
8. Subject will complete the Subject 
Self-Rating Scale (SSRS) (Section 13.1.2.4); 
note this assessment is of both left and right 
buttocks rather than each individual buttock.  
8. Subject will complete the 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 and is 
conducted while viewing images from 
Treatment Visit 4.  
9. Investigator Cellulite Assessments of 
each of the buttock(s) receiving retreatment 
live using: 
9. Subject will complete the Subject 
Self-Rating Scale (SSRS) (Section 13.1.2.5); 
note this assessment is of both left and right 
buttocks rather than each individual buttock. 
a. Clinician Reported Photonumeric 
Cellulite Severity Scale (CR-PCSS) live 
assessment of subject (Section 13.1.2.6) 
10. Investigator Cellulite Assessments will 
be conducted, after the review of training and 
use material for the CR-PCSS, of each of the 
buttock(s) receiving retreatment using: 
a. Clinician Reported Photonumeric 
Cellulite Severity Scale (CR-PCSS) live 
assessment of subject (Section 13.1.2.6) 
After Treatment Visit 4, retreated subjects 
enter/re-enter the observational phase of the 
study with assessments of safety and TRR. If 
an observational visit was scheduled to occur 
during a Treatment Phase visit (Screening B 
through Treatment Visit 4), the observational 
visit would be skipped and the subject would 
enter/re-enter the Observation Phase visits at 
the next interval visit. 

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12.2.1.7.  
Visits 7-11/EOS 
Visits 7-11/EOS and all text in this Section 
Deleted 
Section 12.2.2.1 
Visit 2 (Day 360 
relative to Day 71 
of the double-blind 
study) 
12.2.2.1. Visit 2 (Day 360) 
12.2.2.1. Visit 2 (Day 360 relative to Day 71 
of the double-blind study) 
4. Subjects will get instruction on the use of 
the PR-PCSS (Section 13.1.2.1) 
4. Subjects will get instruction on the use of 
the PR-PCSS (Section 13.1.2.1) and review 
training and use materials for the PR-PCSS, 
the PR-CIS, the SSRS and the Subject 
Satisfaction with Cellulite Treatment 
assessments 
Added 
6. Subject Global Aesthetic Improvement 
Scale (S-GAIS) (Section 13.1.2.2); subjects 
will rate each of their two buttocks while 
viewing pretreatment image from Day 1 of 
the double-blind study (EN3835-302/303) 
9. 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 to remain blinded to these ratings 
10. After the subject has completed the PR 
PCSS ratings and after the Investigator 
reviews the training and use materials for the 
CR-PCSS, 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 to remain 
blinded to these ratings 
Added 
13. Local safety assessments (Section 
14.6.1) 
10. Medical history including EFP history 
(Section 12.1.3) 
Deleted 
Section 12.2.2.2 
Visits 3-7/EOS 
(Day 540-Day 1800 
/EOS) 
12.2.2.2. Visits 3-10/EOS (Day 540 – Day 
1800/EOS) 
12.2.2.2. Visits 3-7/EOS (Day 540 – Day 
1800/EOS) 
Added 
4. Subjects will get instruction on the use of 
the PR-PCSS (Section 13.1.2.1) and review 
training and use materials for the PR-PCSS, 
S-GAIS, PR-CIS, SSRS and the Subject 
Satisfaction with Cellulite Treatment 
assessments 
5.b. Subject Global Aesthetic Improvement 
Scale (S-GAIS) (Section 13.1.2.2); subjects 
will rate each of their two buttocks while 
viewing pretreatment image from Day 1 of 
the double-blind study (EN3835-302/303) 
7. Medical history including EFP history 
(Section 12.1.3) 
Deleted 
Added 
11. Check ePRO for a potential requirement 
for a confirmation visit. 
12. Local safety assessments (Section 14.6.1) 
Section 12.2.2.3 
Confirmation Visits 
Durability of a ≥2-level composite 
improvement in cellulite severity compared 
to the baseline level established during the 
double-blind study will be assessed by both 
the PR-PCSS and the CR-PCSS. If, during 
the study, there is a composite worsening of 
cellulite severity back to baseline levels 
Time to reduction of a ≥1 level and/or 
≥2-level composite improvement in cellulite 
severity compared to the level at Day 71 of 
the double-blind study will be assessed by 
both the PR-PCSS and the CR-PCSS. If, 
during the study, there is a composite 
worsening of cellulite severity of 1-level 

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(ie, worsening of both the PR-PCSS and 
CR-PCSS back to baseline levels), the 
confirmation of loss of response will be 
established during a follow-up visit ~2 
weeks after the loss of response is first 
detected.  
(ie, worsening of both the PR-PCSS and 
CR-PCSS by 1 severity levels), the 
confirmation of loss of response will be 
established during a follow-up visit ~2 weeks 
after the loss of response is first detected. 
2. Subject Cellulite Assessment of each of 
the two buttocks using the photographic 
image (NOTE: complete subject cellulite 
assessments before Investigator cellulite 
assessments) using: 
2. Subject Cellulite Assessment of each of 
the two buttocks, after reviewing the training 
and use materials, using the photographic 
image (NOTE: complete subject cellulite 
assessments before Investigator cellulite 
assessments) using: 
3. Investigator Cellulite Assessments of 
each of the buttocks live using: 
3. Investigator Cellulite Assessments of each 
of the buttocks, after reviewing the training 
and use material, using: 
NOTE: Subjects showing a confirmed 
composite worsening of cellulite severity 
back to baseline levels will no longer require 
efficacy assessments, but should continue 
with annual safety and immunogenicity 
assessments as a Category III subject 
(Days 360, 720, 1080, 1440, and 1800). 
NOTE: Subjects showing a confirmed 
composite worsening of cellulite severity of 
1-level will be offered retreatment and will 
continue with annual safety and 
immunogenicity assessments for up to 
5 years after Day 71. Subjects who do NOT 
show a confirmed composite worsening of 
cellulite will be considered to not have a 
worsening, will not be offered retreatment, 
and will continue with annual safety and 
immunogenicity assessment for up to 5 years 
after Day 71. 
Section 12.3 
Category III 
Subjects Visits 
(Post Unblinding of 
EN3835-302/ 303) 
12.2.3. Category III Subjects 
12.3. Category III Subjects Visits (Post 
Unblinding of EN3835-302/303) 
Category III subjects are to return every 360 
days until they have completed 1800 days 
(5 years) following completion of the 
double-blind study for safety evaluations. 
Category III subjects are to return every 
6 months during the first two years and then 
annually until they have completed 1800 
days (5 years) following Day 71 of the 
double-blind study for safety evaluations. 
3. Medical history including EFP history 
(Section 12.1.3) 
Deleted 
Added 
3. Local safety assessments (Section 14.6.1) 
Section 12.4 
Unscheduled Visit 
Added 
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. 
If unblinding of Investigator, subject and site 
personnel to the treatment that the subject 
received in the double-blind study 
EN3835-302/303 does not occur on Day 180 
Visit after all assessments are completed, 
then an unscheduled visit may be arranged to 
unblind the subject to the treatment received. 
Following unblinding of EN3835 302/303, 
subjects who received placebo will be 
discontinued, and subjects who received 
active EN3835 will be classified into one of 

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three categories based on responder status 
(Section 10.1) and proceed as described in 
Section 12.1.  
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. Any prior use of 
XIAFLEX should also be recorded. 
All prior medications will be recorded; the 
word ‘prior’ refers to the period from the last 
visit from the double-blind study through the 
signing of the informed consent in the 
EN3835-304 study. All concomitant 
medications (including over-the-counter 
medications) including those to treat EFP, 
taken by the subject during the course of the 
EN3835-304 study (ie, after informed 
consent for EN3835-304 is signed) will be 
recorded. 
Section 12.5.1 
Prohibited 
Medications or 
Procedures 
For Category I subjects, the following 
medications are prohibited between Day 360 
and Day 444 (ie, the retreatment phase of the 
study, Table 4): 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. 
For Category I subjects and eligible Category 
II subjects who opt for retreatment, the 
following medications are prohibited during 
the retreatment phase of the study (Table 4): 
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. 
Procedures listed in exclusion criterion #5 
for Category I subjects, and exclusion 
criterion #1 for Category II subjects are 
prohibited for Category I and Category II 
subjects during the study, respectively. 
Procedures listed in exclusion criterion #1 for 
all subjects up through Day 180 Visit, 
exclusion criterion #4 for Category I 
subjects, and exclusion criterion #1for 
Category II subjects are prohibited for all 
subjects up through Day 180 visit, Category I 
and Category II subjects during the study, 
respectively. 
For Category II and Category III subjects, 
this is an observational study to assess 
long-term safety and/or durability of 
response. Since no additional treatments are 
administered, there are no prohibited 
medications. Note that the use of creams, 
procedures, etc as outlined in the exclusion 
criteria (Section 11.2) is prohibited for the 
duration of the study. 
For Category I, Category II and Category III 
subjects, this is an observational study to 
assess long-term safety and/or TRR. The use 
of creams, procedures, etc as outlined in the 
exclusion criteria (Section 11.2) is prohibited 
for the duration of the study. There are no 
additional prohibited medications. 
Section 12.6 
Treatment 
Compliance 
Category I subjects will receive study drug 
administered by an Investigator at the 
Investigator’s site. 
Category I subjects and/or eligible Category 
II subjects may receive study drug 
administered by an Investigator at the 
Investigator’s site. 
For Category II and Category III subjects, 
this study is observational in nature, and no 
additional treatments are to be administered. 
For Category III subjects and Category I and 
Category II subjects that opt not to receive 
treatment, this study is observational in 
nature, and no additional treatments are to be 
administered. 
Section 13.1.1 
Digital 
Photography 
After unblinding of the double-blind studies 
EN3835-302/303, photography will be 
limited to Category I and Category II 
subjects. 
After Day 180 Visit and unblinding of the 
double-blind studies EN3835-302/303, 
photography will be limited to Category I 
and Category II subjects. 

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Section 13.1.2.1 
Patient Reported 
Photonumeric 
Cellulite Severity 
Scale (PR-PCSS) 
The scale is a 5-level photonumeric scale 
developed specifically for patients and used 
by the subject to assess the severity of their 
cellulite by viewing digital images of each of 
their buttocks (or thighs, as applicable) 
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.  
At Screening (eg, Day 71/EOS of the 
double-blind study) and at the beginning of 
each visit where photography is to be 
captured, subjects will have digital 
photographs taken of each of their buttock(s) 
and/or thigh. 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 targeted areas (Appendix B). 
While viewing the digital images of each of 
their buttocks/thigh on a standardized 
computer monitor and using the appropriate  
PR-PCSS for buttock or thigh, subjects will 
be instructed to answer the following 
question for each 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 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.  
At Screening (eg, Day 71/EOS of the 
double-blind study) and at the beginning of 
each visit where photography is to be 
captured, subjects will have digital 
photographs taken of each of their buttock(s). 
Subjects will be given instructions in the 
proper use (Patient Instructions for Use of 
PR-PCSS) of the PR-PCSS, will review 
training and use material, and then perform 
the PR-PCSS for each of the targeted areas 
(Appendix B). While viewing the digital 
images of each of their buttocks on a 
standardized computer monitor and using the  
PR-PCSS for buttock, subjects will be 
instructed to answer the following question 
for each buttock: 
Section 13.1.2.2 
Subject Global 
Aesthetic 
Improvement Scale 
(S-GAIS) 
Added 
13.1.2.2. Subject Global Aesthetic 
Improvement Scale (S-GAIS) 
At each of the visits designated to capture the 
S-GAIS in Section 5.1, Section 5.2, and 
Section 5.3, subjects will review training and 
use materials for S-GAIS, and complete the 
S-GAIS for each of the buttocks as described 
below using the pretreatment Day 1 digital 
image (Baseline) from the double-blind 
studies (EN3835-302/303) 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 pretreatment 
Day 1 digital images from the double-blind 
study (EN3835-302/303) alongside their 
current 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.  

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This variable will be entered directly into the 
ePRO 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. 
−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. 
Section 13.1.2.3  
Patient Reported 
Cellulite Impact 
Scale (PR-CIS) 
At each of the visits designated to capture 
the PR-CIS in Section 5.1, Section 5.2, and 
Section 5.3, 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). 
At each of the visits designated to capture the 
PR-CIS in Section 5.1, Section 5.2, and 
Section 5.3; subjects will review training and 
use materials, and 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-conscience, embarrassed, 
looking older or looking overweight or out 
of shape) using a 6-question survey, with 
each question rated from 0 (not at all) to 
10 (extremely). 
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 from 0 (not at all) to 
10 (extremely). 
Added 
This variable will be entered directly into the 
ePRO system, thus the electronic database 
will serve as the direct point of data capture 
and will serve as source for this variable 
Section 13.1.2.4 
Subject Satisfaction 
with Cellulite 
Treatment 
Assessment 
At the designated visits, 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 5). 
At the designated visits, subjects will review 
training and use materials and 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). 
This variable will be entered directly into the 
EDC system, thus the electronic database 
This variable will be entered directly into the 
ePRO system, thus the electronic database 

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will serve as the direct point of data capture 
and will serve as source for this variable. 
will serve as the direct point of data capture 
and will serve as source for this variable. 
Section 13.1.2.5 
Subject Self-Rating 
Scale (SSRS) 
The patient will be asked to respond to the 
question related to the satisfaction with 
appearance of the cellulite on their buttocks. 
The subject will review training and use 
materials for the SSRS. The subject will be 
asked to respond to the question related to the 
satisfaction with appearance of the cellulite 
on their buttocks 
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. 
This variable will be entered directly into the 
ePRO system, thus the electronic database 
will serve as the direct point of data capture 
and will serve as source for this variable. 
Section 13.1.2.6 
Clinician Reported 
Photonumeric 
Cellulite Severity 
Scale (CR-PCSS) 
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 (or thigh, where applicable) 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 Day 71 visit during the double-blind 
study (which also serves as the Screening 
visit for the current study), 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 (Appendix C). 
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. Investigators will review 
training and use materials at each visit prior 
to the use of the CR-PCSS. 
At the Day 71 visit during the double-blind 
study (which also serves as the Screening 
visit for the current study), the Investigator 
will determine severity of cellulite of each of 
the two buttocks via live assessment of the 
subject using the CR PCSS for the buttock 
(Appendix C) after the subject has completed 
her self-assessment using the PR-PCSS for 
the buttock (Appendix B). 
Section 14.5.1 
Reporting Adverse 
Events 
Conditions existing prior to screening will be 
recorded as part of the subject’s medical 
history. 
Deleted 
Section 14.6.1 
Adverse Events of 
Special Interest 
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) 
In addition, local AEs associated with the 
injection site (whether the site was injected in 
the double-blind study (EN3835/302/303) or 
in this open-label study (EN3835-304)), 
including acute (eg, erythema, bruising, pain, 
nodules/mass, ulceration, blistering, pruritus, 
swelling, and/or induration) and/or chronic 
(eg, skin thickening, fibrosclerosis, peau 
d’orange changes) cutaneous adverse events, 
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). 
Section 14.7 
Clinical Laboratory 
Determinations 
For women of childbearing potential, a 
serum pregnancy test will be performed at 
the Day 71 visit from the double-blind study 
(EN3835-302 or EN3835-303), and urine 
pregnancy tests will be performed at the 
For women of childbearing potential, a serum 
pregnancy test will be performed at the Day 
71 visit from the double-blind study 
(EN3835-302 or EN3835-303), the results of 
which will be data transferred to the 

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other study visits (refer to Section 5.1 and 
Section 5.2). 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. 
Screening Visit of this open-label study if the 
Screening Visit occurs within 14 days of the 
Day 71 visit of the double-blind study. 
Additionally, a serum pregnancy test will be 
performed at the Screening B visit of any 
Category I and/or eligible Category II subject 
screening for the Treatment phase of the 
study. Urine pregnancy tests will be 
performed at the other study visits (refer to 
Section 5.1 and Section 5.2). 
Section 14.8  
Anti-AUX-I and 
Anti-AUX-II 
Antibodies 
For Category I subjects receiving 
retreatment, a subset (based on every other 
sample from the Visit 6 [Day 444] upper and 
lower quadrants of binding antibody titers) 
of subject samples will be tested for 
neutralizing antibodies from these visits; 
additional samples will be retained.  
For Category I subjects and/or eligible 
Category II subjects receiving retreatment, a 
subset (based on every other sample from the 
Treatment Visit 4 upper and lower quadrants 
of binding antibody titers) of subject samples 
will be tested for neutralizing antibodies from 
these visits; additional samples will be 
retained. 
Section 14.9  
Vital Signs 
For Category I subjects receiving 
retreatment, vital signs will be assessed at 
the time points shown in Table 8 after the 
subject has rested for at least 5 minutes. 
For Category I and/or eligible Category II 
subjects receiving retreatment, vital signs 
will be assessed at the time points shown in 
Table 9 after the subject has rested for at 
least 5 minutes. 
Section 14.10 
Electrocardiogram 
No ECGs are to be performed during this 
study. 
Performing a 12-lead electrocardiogram 
(ECG) is not necessary if Screening B visit 
date is within 12 months of obtaining an 
ECG during the double-blind study 
(EN3835-302/303). 
If the date of Screening B visit is later than 
12 months since obtaining the ECG in study 
EN3835-302/303, subjects will have a resting 
12-lead ECG performed during the Screening 
B visit. 
A qualified physician will interpret, sign, and 
date the ECGs. Electrocardiogram 
assessments must be “within normal limits” 
or interpreted as “abnormal, not clinically 
significant” for the subject to be included in 
the study. 
 
Any ECG result 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). 
Section 14.11 
Physical 
Examination 
Height and body weight will be measured at 
additional Visits for Category I subjects (in 
the absence of a full physical exam) as 
designated in Section 5.2. 
Height and body weight will be measured at 
additional visits for Category I and 
retreatment-eligible Category II subjects (in 
the absence of a full physical exam) as 
designated in Section 5.2. 
Section 17.1 
Determination of 
Sample Size 
Approximately 420 subjects completed the 
EN3835-302/303studies will rollover to this 
study. This sample size should be adequate 
Approximately 420 active subjects who 
completed the EN3835-302/303studies will 
rollover to this study. This sample size 

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to determine long-term safety and cellulite 
assessments of EN3835 for durability. 
should be adequate to determine long-term 
safety and TRR of EN3835. 
Section 17.2 
Subject Populations 
For subjects entering open-label study 
period, subjects who received active EN3835 
in their double-blind studies (EN3835-302/ 
303) will be classified into 3 categories: 
Category I: 1-level Composite Responders 
Category II: 2-Level Composite Responders 
Category III: Non-Composite Responders 
Based on subject category, two (2) 
populations are considered in the statistical 
analysis of the study: overall safety 
population and durability population. 
For subjects entering the open-label study 
period, subjects who received active EN3835 
in their double-blind study (EN3835-302/ 
303) will be classified into one of three 
categories:  
Category I: 1-Level Composite Responders 
Category II: 2-Level Composite Responders 
Category III: Non-Composite Responders 
Based on subject category, two (2) 
populations are considered in the statistical 
analysis of the study: overall safety 
population and time to reduction in response 
population. 
Section 17.2.1 
Overall Safety 
Population 
The overall safety population is defined as 
all rollover subjects who enter the open-label 
study period. This population will include all 
Category I, II, and III subjects. In addition, 
the safety data will be summarized by 
treatment period for those re-treated subjects 
with EN3835. Safety will be assessed for up 
to approximately 5 years from first exposure, 
and for Category I re-treated subjects, 
approximately 4 years following retreatment. 
The overall safety population is defined as all 
subjects who enter the open-label study 
period and received EN3835 in EN3835-302 
or EN3835-303. This population will include 
all Category I, II, and III subjects. All safety 
analyses will be based on this population. In 
addition, the safety data will be summarized 
by treatment period for those retreated 
subjects with EN3835. 
Section 17.2.2 Day-
180 Observational 
Population 
Added 
The Day-180 observational population will 
include all rollover subjects from studies 
EN3835-302/303. The safety analysis for the 
data obtained from Screening to Day 180 will 
be based on this population. 
Section 17.2.3 
Time to Reduction 
of Response (TRR) 
Population 
17.2.2. Durability Population 
17.2.3. Time to Reduction of Response 
(TRR) Population 
The durability population is defined as all 
subjects who have at least a 1 or 2-level 
improvement in both CR-PCSS and 
PR-PCSS scores/ratings during the double-
blind study for either/both treated buttocks. 
This population will include Category I and 
II subjects. The durability data will be 
collected up to 6 months for Category I 
subjects and up to 5 years (1800 days 
following Day 71 of the double-blind study) 
for category II subjects. 
The TRR population is defined as all subjects 
who have at least a 1-level or 2-level 
improvement in both CR-PCSS and 
PR-PCSS ratings during the double-blind 
study for either/both treated buttocks. This 
population will include Category I and II 
subjects. 
Section 17.4 
Demographics and 
Other Baseline 
Characteristics 
Added 
These data will be transferred from 
EN3835-302 and EN3835-303 and will 
pre-populate the relevant fields of the 
database for this open-label study. 
Section 17.5 
Efficacy Analyses 
• PR-PCSS: a subject reported 5-point scale 
ranging from 0 (no cellulite) to 4 (severe 
cellulite). 
• PR-PCSS: patient reported 5-point scale 
ranging from 0 (no cellulite) to 4 (severe 
cellulite). 

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Section 
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Revised Text 
• CR-PCSS: an investigator reported 5-point 
scale ranging from 0 (no cellulite) to 4 
(severe cellulite). 
• CR-PCSS: clinician reported 5-point scale 
ranging from 0 (no cellulite) to 4 (severe 
cellulite). 
• PR-CIS: a subject reported scale to 
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 
from 0 (not at all) to 10 (extremely). A PR-
CIS total score and an abbreviated PR CIS 
score (excluding question 5) will be derived 
from these 6 individual questions. 
• PR-CIS: patient reported cellulite impact 
scale to assess 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 
from 0 (not at all) to 10 (extremely). A PR-
CIS total score and an abbreviated PR CIS 
score (excluding question 5) will be derived 
from these 6 individual questions. 
 
• Subject Global Aesthetic Improvement 
Scale (S-GAIS): a 7-level scale ranging from 
3 (very much improved) to −3 (very much 
worse). 
All cellulite assessments will be done by 
treated areas, each quadrant will be 
evaluated separately. 
All cellulite assessments will be performed 
on each individual treatment area. Treatment 
areas will be evaluated separately. 
Section 17.5.1 
Analyses 
The analyses of cellulite assessments will be 
based on durability population. The 
durability of response will be defined from 
the accessing of the efficacy (Day 71 at 
EN3835-302/303) to the loss of response 
study visit. 
The analyses of cellulite assessments will be 
based on the TRR population. The TRR will 
be defined from time of assessing the 
efficacy (Day 71 at EN3835-302/303) to the 
study visit at which a composite 1-level 
reduction of response in both PR-PCSS and 
CR-PCSS is observed. 
The defined endpoints will include: 
The defined endpoints will include: 
• Proportion of subjects who lose their 
responses: 
• Proportion of subjects with reduction of 
response: 
- Proportion of subjects that both CR-PCSS 
and PR-PCSS scores/ratings are back to their 
baseline or worse 
- Proportion of subjects with both CR-PCSS 
and PR-PCSS ratings worsening 1-level 
compared to their corresponding score at Day 
71 in the double-blind studies (EN3835-
302/303) 
- Proportion of subjects that both CR-PCSS 
and PR-PCSS scores/ratings are worsening 
2- levels comparing to their corresponding 
score at Day 71 in the double-blind studies 
(EN3835-302/303) 
- Proportion of subjects with both CR-PCSS 
and PR-PCSS ratings back to their baseline 
(Day 1 of the double-blind study) or worse 
- Proportion of subjects that either CR-PCSS 
or PR-PCSS scores/ratings are worsening 2-
levels comparing to their corresponding 
score at Day 71 in the double-blind studies 
(EN3835-302/303) 
- Proportion of subjects with both CR-PCSS 
and PR-PCSS ratings worsening 2-levels 
compared to their corresponding score at Day 
71 in the double-blind studies (EN3835-
302/303) 
- Subjects that both CR-PCSS and PR-PCSS 
scores/ratings are worsening 1-level 
comparing to their corresponding score at 
Day 71 in the double-blind studies (EN3835-
302/303) 
- Proportion of subjects with either CR-PCSS 
or PR-PCSS ratings worsening 2-levels 
compared to their corresponding score at Day 
71 in the double-blind studies (EN3835-
302/303) 
All results for each endpoint based on the 
collection time points as scheduled in 
All results for each endpoint based on the 
collection time points as described in 

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Section 
Original Text 
Revised Text 
Section 5.1, Section 5.2, and Section 5.3 will 
be derived and be summarized by treated 
area , subject category, and study visit (day) 
using appropriate descriptive statistics. 
Section 5.1, Section 5.2, and Section 5.3 will 
be derived and be summarized by treated 
area, subject category, and study visit (day) 
using appropriate descriptive statistics. 
Section 17.6  
Safety Analyses 
Injection site reactions/local tolerability in 
treated quadrant (through subject and 
Investigator reporting) 
Injection site reactions/local tolerability in 
treatment area (through subject and 
Investigator reporting) 
AEs will be summarized by subject category 
using descriptive statistics. In addition, the 
safety data will be summarized by treatment 
period for those re-treated subjects. 
Descriptive statistics will be presented for 
each clinical laboratory test for the actual 
and change from screening at each visit by 
subject category and vital signs for the actual 
and change from screening at each visit by 
subject category. 
AEs will be summarized by treatment 
exposure category, ie, initial exposure to 
EN3835 in EN3835-302/303 versus 
re-exposure to EN3835 in this open-label 
study (EN3835-304) using descriptive 
statistics. 
Section 17.6.4  
Vital Signs 
Vital sign values are potentially clinically 
significant (PCS) if they meet both the 
observed value criteria and the change from 
baseline criteria. The criteria for PCS vital 
sign values will be detailed in the Statistical 
Analysis Plan (SAP). 
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). 
Section 17.6.5 
Clinical Laboratory 
Parameters 
The number and percentage of subjects with 
PCS post-baseline clinical laboratory values 
will be tabulated. The criteria for PCS 
laboratory values will be detailed in the 
SAP. A listing of all AEs for subjects with 
PCS laboratory values will also be provided. 
The number and percentage of subjects with 
PCI post-baseline clinical laboratory values 
will be tabulated. The criteria for PCI 
laboratory values will be detailed in the SAP. 
A listing of all subjects with PCI laboratory 
values will also be provided. 
Section 17.7 
Immunogenicity 
Analyses 
Descriptive statistics (percent of positive 
measurements and average antibody level) 
will be presented for anti-AUX-I and anti-
AUX-II antibody levels at each time point by 
treated area and by subject category. 
Average antibody levels will be summarized 
on logarithmically transposed titer values. 
Descriptive statistics (percent of positive 
measurements and average antibody level) 
will be presented for anti-AUX-I and anti-
AUX-II antibody levels at each time point by 
treated area and by treatment exposure 
category. Average antibody levels will be 
summarized on logarithmically transposed 
titer values. 
In addition, a subset of subjects with 
neutralizing anti-AUX-I and anti-AUX-II 
antibody levels will be summarized by 
subject category using the binary response 
(positive/negative). 
In addition, a subset of subjects’ samples 
with anti-AUX-I and anti-AUX-II 
neutralizing antibodies will be summarized 
using appropriate descriptive statistics. 
Section 18.2  
Study Drug 
Packaging and 
Labeling 
Each vial of study drug and diluent will 
minimally be labeled with contents, Sponsor 
identification, storage, administration/use, 
kit number, and appropriate cautions 
statements 
Each vial of study drug and diluent will 
minimally be labeled with contents, Sponsor 
identification, storage, administration/use, 
and appropriate cautions statements; 
additionally, study drug will be labeled with 
kit number 
Section 18.4  
Study Drug 
Preparation 
Dispose of used diluent vials, needles, and 
syringes per local regulations. 
Dispose of used needles and syringes per 
local regulations. 

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Section 
Original Text 
Revised Text 
Section 19.1 
Source Documents 
Added 
S-GAIS 
Section 21.3 
Subject 
Information and 
Consent 
A unique Subject identification number will 
be carried over from the double-blind, 
placebo controlled study (EN3835-302/303). 
The unique subject identification number will 
be carried over from the double-blind, 
placebo controlled study (EN3835-302/303). 

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3. 
SPONSOR CONTACT INFORMATION 
Table 1: 
Sponsor Contact Information 
Role in Study 
Name 
Telephone and Email Address 
Clinical Development Lead  
 
Office: 
 
Cell:  
Not applicable 
Clinical Trial Lead 
 
 
Office: 
 
Cell: 
Not applicable 
Email: 
 
Medical Monitor 
 
 
Office: Not applicable  
Cell: 
  
Email: 
 
SAE Reporting Pathway 
Not Applicable 
FAX: 
 
Email: 
 
A list of other key study personnel and vendors will be provided separately for your reference. 

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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 3b, Open-label, Long-term Study to Evaluate the Safety and Temporal 
Pattern of Response of EN3835 in the Treatment of Edematous Fibrosclerotic Panniculopathy 
Lead Principal Investigator: Not applicable 
Study Period:  
Estimated date first subject enrolled:  
April 2018 
Estimated date last subject completed:  
December 2021  
Phase of Development: 3b 
Primary Objectives:  
• 
To assess the long-term safety of EN3835 in the treatment of edematous fibrosclerotic 
panniculopathy (EFP) commonly known as cellulite in adult women. 
• 
To assess the safety of EN3835 when used for retreatment in the treatment of EFP commonly 
known as cellulite in adult women. 
• 
To assess the long-term immunogenicity profile of EN3835 following treatment of EFP 
commonly known as cellulite in adult women. 
Secondary Objectives: 
To assess the time to reduction of response (TRR) to EN3835 in the treatment of EFP in adult 
women. 
Study Design: 
This open-label extension study will be performed at multiple centers currently participating in the 
double-blind, placebo-controlled, parent trials (EN3835-302/EN3835-303) in the United States. The 
open-label extension study will initially enroll up to 840 subjects until the double-blind studies are 
unblinded, after which only subjects who received active EN3835 will remain in observation in the 
current study. Subjects who completed the double-blind study and sign an informed consent will be 
eligible to enter this open-label extension.  
Following completion of safety and cellulite assessments (at least Patient Reported Photonumeric 
Cellulite Severity Scale [PR-PCSS] and the Clinician Reported Photonumeric Cellulite Severity Scale 
[CR-PCSS]) at Day 71 of the double-blind study (EN3835-302/303), subjects will be asked to 
continue in the open-label extension to the double-blind study (ie, EN3835-304, the current study). At 
the time of entry into the open-label study and at Visit 1 at Day 180 of study EN3835-304 
(approximately 6 months after Day 71 of study EN3835-302/303), subjects, Investigators and site 
personnel will remain blinded to study drug treatment received in the double-blind study. 
Upon unblinding of the double-blind studies EN3835-302/303 (which may occur immediately after 
Day 180 Visit assessments are completed if the study drug blind has been broken by Sponsor, or may 
occur during a visit (Unscheduled Visit) after the Day 180 Visit if the blind is not broken by Sponsor 
until sometime after Day 180), subjects who received placebo during the double-blind studies will be 
discontinued, and subjects who received active EN3835 will be classified into one of three categories: 
Category I: 
1-Level Composite Responders 
Category II: 
2-Level Composite Responders 
Category III: Non-Composite Responders 
Category I will include subjects in which the maximum composite response in either (or both) 
buttock(s) in EN3835-302 or EN3835-303 was ONLY a 1-level composite improvement in cellulite 
severity as assessed by the PR-PCSS and the CR-PCSS. Category I subjects will be eligible for one 
additional retreatment course in up to two buttocks in the current open-label study. Retreatment may 
begin on Day 180 if the study drug blind from the double-blind study (EN3835-302/303) has been 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
broken. Only buttocks with a composite 1-level improvement or less will be retreated. Assessment of 
open-label efficacy following retreatment will be determined up to Treatment Visit 4 (Day 71 + 
5 days), after which subjects will be observed for every 6 months for 2 years and then annually for up 
to 3 years (Day 1080) after Day 71 of study EN3835-302/303.  
Category II will include subjects who showed an improvement in cellulite severity of at least two 
levels in at least one buttock in both the PR-PCSS and the CR-PCSS (ie, 2-level composite responder) 
in EN3835-302 or EN3835-303. These subjects will be observed for TRR (defined below) and safety 
approximately every 6 months for 2 years and annually for up to 3 years (Day 1080) from Day 71 of 
the double-blind studies. Category II subjects must have at least a 1-level composite response 
reduction compared to Day 71 of the EN3835-302/303 study AND no longer maintain a 2-level 
composite response compared to baseline in the EN3835-302/303 study on either or both buttocks to 
be eligible for retreatment. Assessment of open-label efficacy following retreatment will be 
determined up to Treatment Visit 4 (Day 71 + 5 days), after which subjects will be observed for 
safety every 6 months for 2 years and then annually for up to 3 years (Day 1080) after Day 71 of 
study EN3835-302/303. 
Category I and Category II subjects who chose not to be retreated will have cellulite assessments 
completed during the observational visits at Months 12, 18, 24, and 36. At Months 12, 18, 24, and 36, 
if the ratings indicate that the buttock(s) is/are eligible for retreatment and the subject has not received 
EN3835 previously in study EN3835-304, the subject will be offered one course of retreatment for the 
eligible buttock(s).  
Category III subjects will include all other subjects who received active EN3835 in study 
EN3835-302 or EN3835-303 but did not meet criteria to be included in Category I or II 
(ie, noncomposite responders). These subjects will be observed for safety every 6 months for 2 years 
and annually for up to 3 years (Day 1080) and will not be eligible for retreatment during the study. 
The retreatment course for eligible Category I and Category II subjects will consist of 3 treatment 
sessions separated by 21 days. Each retreatment session will consist of 12 injections (0.07 mg/0.3 mL 
per injection) of EN3835 for a dose of 0.84 mg and volume of 3.6 mL (identical to the treatment 
course administered in the double-blind study), in each qualifying buttock in up to two buttocks 
treated concurrently. One and only one retreatment course in up to 2 qualifying buttocks concurrently 
will be offered to eligible Category I and Category II subjects during this 3 year study.  
Number of Subjects (Planned): Up to approximately 420 active subjects. 
Study Center(s): Approximately 50 sites in United States 
Diagnosis and Inclusion/Exclusion Criteria: 
All Subjects (Through Day 180): 
Subjects who completed the double-blind Phase 3, study EN3835-302 or EN3835-303, are judged to 
be in good health, are willing to apply sunscreen to both buttocks before sun exposure, have not 
received collgenase or any EFP treatments to the buttocks since the completion of study EN3835-
302/303, and will not receive other EFP treatments to the buttocks will be eligible to enroll in this 
period. 
Category I Subjects: 
Subjects whose maximum composite response at Day 71 in either or both buttocks in double-blind 
study EN3835-302 or EN3835-303 was ONLY a 1-level improvement on CR-PCSS/PR-PCSS, are in 
good health, are willing to apply sunscreen to both buttocks before sun exposure, will not receive 
other EFP treatments to the buttocks, and have not received any collagenase treatments since the 
completion of studies EN3835-302/303 were eligible to continue in 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 
Category II Subjects: 
Subjects who had a maximum composite response at Day 71 in either or both buttocks in double-
blind study EN3835-302 or EN3835-303 was at least a 2-level composite improvement on CR-PCSS/ 
PR-PCSS, are in good health, are willing to apply sunscreen to both buttocks before sun exposure, 
will not receive other EFP treatments to the buttocks and have not received any collagenase 
treatments since the completion of studies EN3835-302/303 are eligible to continue in the study. 
Category III Subjects: 
Received active EN3835 in study EN3835-302 or EN3835-303 but did not meet eligibility criteria for 
Category I or Category II status are eligible to continue in the study. 
Category I and Category II Subjects Who Opt to Receive Retreatment: 
Category I and Category II subjects who meet all entry criteria outlined above can opt to receive 
retreatment if they have a negative serum pregnancy test at screening and a negative urine pregnancy 
test prior to any dose and agree to use an acceptable means of birth control during retreatment. In 
addition, Category II subjects must have had at least a 1-level composite response reduction 
compared to Day 71 of the EN3835-302/303 study AND no longer maintain a 2-level composite 
response compared to baseline in the EN3835-302/303 study on either or both buttocks. 
Subjects will be excluded from retreatment if they have ineligible systemic disorders, history of local 
conditions in the area to be treated, require anticoagulant or antiplatelet medications (except ≤150 mg 
aspirin daily), are nursing (during active retreatment only), intend to use tanning spray or tanning 
booths in the 30 days prior to or during treatment, or have a known systemic allergy to collagenase. 
Investigational Product, Dosage and Mode of Administration: EN3835, up to 1.68 mg, 
subcutaneous. A dose of 0.84 mg of EN3835 per buttock will be administered as 12 subcutaneous 
injections (0.3-mL injections administered as three 0.1-mL aliquots per injection) in each qualifying 
buttock, for a total dose of up to 1.68 mg and a total volume of up to 7.2 mL (3.6 mL per buttock). 
Total number of injections will be up to 24 injections per treatment visit in up to two buttocks 
(ie, 12 injections per buttock). For subjects who qualify for retreatment, there will be 3 treatment 
visits at 21-day intervals, beginning 6 months after Day 71 in their respective double-blind study 
(EN3835-302/303). 
Duration of Study: 
Up to thirty-six (36) months from Day 71 (approximately 28 days after their last exposure to EN3835) 
of the study EN3835-302/303. 
Criteria for Evaluation: 
Cellulite assessments (efficacy) will include PR-PCSS, CR-PCSS: Patient Reported Cellulite Impact 
Scale (PR-CIS) and an abbreviated PR-CIS, Subject Global Aesthetic Improvement Scale (S-GAIS), 
and Subject Satisfaction with Cellulite Treatment Assessment and Subject Self-Rating Scale (SSRS). 
Cellulite assessments of PR-PCSS, CR-PCSS and S-GAIS will be performed on each buttock. Each 
buttock will be evaluated separately. Cellulite assessment of PR-CIS, Subject satisfaction with 
cellulite treatment assessment, and SSRS will be performed on both buttocks. 
Time to Reduce a 2-Level Composite Response: 
For the purposes of this study, a subject treated with EN3835 is considered a 2-level composite 
responder once an improvement of at least 2 levels on each assessment scale (PR-PCSS/CR-PCSS) is 
shown at the same visit during the double-blind study at or before Day 71 in either or both buttocks. 
The time until a reduction of response has occurred is considered to end once a subject’s cellulite 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
severity improvement reduces a composite 1-level, ie, a reduction in severity by 1-level in both the 
PR-PCSS and CR-PCSS. 
Safety: 
Safety will be assessed throughout the study by Adverse events (AEs) (including adverse events of 
special interest [AESI]), vital signs (at retreatment visits), clinical laboratory tests (prior to 
retreatment visits and 28 days after the last retreatment dose), immunogenicity assessments 
(ie, assessed through the determination of binding and neutralizing anti-AUX-I and anti-AUX-II 
antibody levels). In addition, for subjects treated with study drug in this study, injection site 
reactions/local tolerability in the treated buttocks (through subject and Investigator reporting) will be 
assessed. 
Statistical Methods: 
Analysis Populations: 
Overall Safety Population: All subjects who enter the open-label study period and received EN3835 
in study EN3835-302 or EN3835-303. This population will include all Category I, II, and III subjects. 
All safety analyses will be based on this population. 
Day-180 Observational Population: All rollover subjects from studies EN3835-302/303. The safety 
analysis for the data obtained from Screening to Day 180 will be based on this population. 
TRR: All subjects who have at least 1-level/2-level improvement in both CR-PCSS and PR-PCSS 
ratings during the double-blind study for either/both treated buttocks. This population will include 
Category I and II subjects. The TRR data will be collected for up to 3 years for Category I and II 
subjects. 
Efficacy Analyses: 
The analyses of cellulite assessments will be based on the TRR population. The TRR will be defined 
from the time of assessing the efficacy (Day 71) in the double-blind study (EN3835-302/303) until 
the study visit in study EN3835-304 at which a composite 1-level loss of response in both PR-PCSS 
and CR-PCSS is observed.  
The defined endpoints will include: 
• 
Proportion of subjects with reduction of response 
- 
Proportion of subjects with both CR-PCSS and PR-PCSS ratings worsening 1-level 
compared to their corresponding score at Day 71 in the double-blind study (EN3835-302/ 
303) 
- 
Proportion of subjects with both CR-PCSS and PR-PCSS ratings back to their baseline or 
worse 
- 
Proportion of subjects with both CR-PCSS and PR-PCSS ratings worsening 2-levels 
compared to their corresponding score at Day 71 in the double-blind study (EN3835-302/ 
303) 
- 
Proportion of subjects with either CR-PCSS or PR-PCSS ratings worsening 2-levels 
compared to their corresponding score at Day 71 in the double-blind study (EN3835-302/ 
303) 
• 
Proportion of subjects at each level of improvement in the PR-PCSS 
• 
Proportion of subjects at each level of improvement in the CR-PCSS 
• 
Changes in the PR-CIS total scores from baseline 
• 
Proportion of subjects at each level of improvement in the S-GAIS 
• 
Proportion of subjects at each level of improvement in the subject satisfaction with cellulite 
treatment 

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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 subjects at each level of improvement in the SSRS 
All results for each endpoint based on the collection time points will be derived and be summarized 
by treated area, treatment exposure category, and study visit (day) using descriptive statistics.  
Safety Analyses: 
AEs will be summarized by proportion of subjects reporting each event. Descriptive statistics will be 
presented for actual and change from baseline at each visit for vital signs and for each clinical 
laboratory test parameter. 
Immunogenicity:  
Anti-AUX-I and anti-AUX-II antibody levels and a subset of subjects’ samples anti-AUX-I and anti-
AUX-II neutralizing antibodies will be summarized using descriptive statistics. 

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5. 
SCHEDULE OF EVENTS 
5.1. 
Up to 180 Days 
Proceduresa 
Screening Ab 
(≥Day 71 Visit of 
Double-blind 
Study) 
(+14 days) 
Visit 1 
Day 180c 
(±14 days) 
M6/Early 
Termination 
Durability 
Confirmation 
Visitd  
Unblinding of Investigator, subject and site to subjects’ treatments in EN3835-302/303e 
 
X 
 
Informed consentf 
X 
X 
 
Inclusion/exclusion 
X 
 
 
Digital photography 
X 
X 
X 
Prior/concomitant medications/proceduresg  
X 
X 
 
Physical examination: 
X 
 
 
• Body weight 
X 
X 
 
• Height  
X 
 
 
Vital signs 
X 
X 
 
Collection of Samples 
 
 
 
• Clinical laboratory 
X 
X 
 
• Anti-AUX-I/anti-AUX-II antibody level 
X 
 
 
• Pregnancy testingh  
X 
X 
 
Subject Cellulite Assessments  
 
 
 
• Review assessments’ training and use materials 
X 
X 
X 
• Patient Reported Photonumeric Cellulite Severity Scale (PR-PCSS)i,j 
X 
X 
X 
• Subject Global Aesthetic Improvement (S-GAIS) k,l 
X 
X 
 
• Patient Reported Cellulite Impact Scale (PR-CIS) m,n 
X 
X 
 
• Subject Satisfaction With Cellulite Treatment Assessmento,p 
X 
X 
 
• Subject Self-Rating Scale (SSRS) 
X 
X 
 
Investigator Cellulite Assessments 
 
 
 
• Review assessment’s training and use materials 
X 
X 
X 
• Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS)q  
X 
X 
X 
Assignment of Subject to Category I, II, or IIIr 
 
X  
 
Local safety assessmentss 
X  
X  
X 
Adverse eventst 
Monitored throughout study 

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a Unscheduled visits may be done as deemed necessary at any time during the study to ensure subject safety; assessments done at unscheduled visits are at the 
discretion of the investigator. No photographs or cellulite severity assessments will be done at unscheduled visits. 
b Day 71 Visit in the double-blind study (EN3835-302/303). 
c Visit 1 Day 180 is in study EN3835-304; approximately 180 days after Day 71 of double-blind study. A subject who terminates study participation between 
Day 71 and Day 180 will have an Early Termination Visit that includes the Assessments listed for Visit 1 Day 180. 
d If the composite (CR-PCSS and PR-PCSS) ratings worsen by at least 1-level composite response ratings at the Day 180 Visit or at a subsequent unscheduled 
unblinding visit for a subject that had a 2-level composite improvement at Day 71 of the double-blind study, an additional visit should be scheduled 14 days 
(± 5 days) later to confirm reduction of response, via re-assessment with the CR-PCSS and PR-PCSS. 
e Depending on the date of unblinding of subject’s treatment in EN3835-302/303; investigators, subjects, and site personnel may be unblinded at Day 180 Visit 
AFTER all assessments have been performed or at a time thereafter during an unscheduled visit. If database lock occurs prior to Day 180, the investigator, 
subjects, and site personnel will remained blinded until the Day 180 Visit. 
f Informed consent at Screening will address activities up through Day 180 Visit. Informed consent at Day 180 Visit will address the classification of subjects 
into Categories I, II, and III and activities and assessments that they will undergo. 
g Including XIAFLEX as a concomitant medication; the use of the word ‘prior’ refers to the period between the last visit from the previous Phase 3 clinical study 
through the signing of informed consent in the EN3835-304 study; not applicable to subjects who sign consent for this study on the same day that they 
complete the EN3835-302/303 study.  
h Serum pregnancy tests occur during the Screening Visit (carried over from Day 71/EOS visit of EN3835-302/303); urine pregnancy test on Day 180 Visit and, 
if deemed necessary, at an Unscheduled Visit.  
i Subject assessments should be completed independently and prior to Investigator assessments at each visit. 
,j Assessment made via photographs.  
q Assessment of each of the 2 buttocks independently.  
r Assignment of subjects to Categories will occur after unblinding of investigators, subject and site personnel to subjects’ treatment in EN3835-302/303 and will 
depend on treatment and Day 71 cellulite severity improvements. Depending on the date of the database lock of the double-blind studies, assignments may 
occur at the Day 180 Visit after assessments are completed or at a time thereafter during an unscheduled visit. 
s Local adverse events associated with the injection site, including acute (eg, erythema, bruising, pain, nodules/mass, ulceration, blistering, pruritus, swelling, 
and/or induration) and/or chronic (eg, skin thickening, fibrosclerosis, peau d’orange changes) cutaneous adverse events, will be recorded and evaluated for 
seriousness and severity. 
t Any AE that occurs between the completion of studies EN3835-302/303 and the Day 180 Visit will be reported and evaluated. 
EFP=Edematous fibrosclerotic panniculopathy; EOS=End of study; M=Month(s). 

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5.2. 
Eligible Category I/II Subjects – Treatment Session Assessments 
Proceduresa  
Screening Bb 
(Day -14 to -
1 relative to 
Tx Visit 1) 
Tx Visit 1 
Tx Session 1 
Day 1 
Tx Visit 2 
Tx Session 2 
Day 22 (±3 days) 
Tx Visit 3 
Tx Session 3 
Day 43 (±3 days) 
Tx Visit 4 
End of Treatment 
Day 71 (+5 days)c  
Informed consentd 
X  
 
 
 
 
Inclusion/exclusion 
X 
 
 
 
 
Digital photographye 
X  
Xf  
Xf  
Xf  
X  
Prior/concomitant medications/proceduresg  
X 
X 
X 
X 
X 
Physical examination: 
X 
 
 
 
 
• Body weight 
X 
 
Xh  
Xh  
X 
• Height  
X 
 
 
 
 
Vital signs 
X 
Xi 
Xi 
Xi 
X 
ECGj 
X  
 
 
 
 
Collection of Samples 
 
 
 
 
 
• Clinical laboratory 
X 
 
 
 
X 
• Anti-AUX-I/anti-AUX-II antibody level 
X 
 
X 
X 
X 
• Pregnancy testingk  
X  
Xh 
Xh 
Xh  
X  
Subject Cellulite Assessments  
 
 
 
 
 
• Review assessments’ training and use materials 
X 
X 
X 
X 
X 
• Patient Reported Photonumeric Cellulite Severity 
Scale (PR-PCSS)l,m 
X 
X  
X  
X  
X 
• Subject Global Aesthetic Improvement Scale 
(S-GAIS)l  
X 
 
 
 
X 
• Patient Reported Cellulite Impact Scale (PR-CIS)l 
X 
 
 
 
X 
• Subject Satisfaction With Cellulite Treatment 
Assessmentl 
X 
 
 
 
X 
• Subject Self-Rating Scale (SSRS)l 
X 
 
 
 
X 
Investigator Cellulite Assessments 
 
 
 
 
 
• Review assessment’s training and use materials 
X 
X 
X 
X 
X 
• Clinician Reported Photonumeric Cellulite Severity 
Scale (CR-PCSS)  
X 
X 
X 
X 
X 
Selection of dimples to be treated  
 
X 
X 
X 
 

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Proceduresa  
Screening Bb 
(Day -14 to -
1 relative to 
Tx Visit 1) 
Tx Visit 1 
Tx Session 1 
Day 1 
Tx Visit 2 
Tx Session 2 
Day 22 (±3 days) 
Tx Visit 3 
Tx Session 3 
Day 43 (±3 days) 
Tx Visit 4 
End of Treatment 
Day 71 (+5 days)c  
Marking the dimples and injection sites to be treated 
within the buttocks 
 
X 
X 
X 
 
Confirm eligibility of buttocks for retreatmentn 
X 
 
 
 
 
Study drug administration  
 
X 
X 
X 
 
Injection site reactions/local tolerability in the buttockso 
 
X 
X 
X 
X 
Adverse events 
Monitored throughout study 
a Unscheduled visits may be done as deemed necessary at any time during the study to ensure subject safety; assessments done at unscheduled visits are at the 
discretion of the investigator. No photographs or cellulite severity assessments will be done at unscheduled visits. 
bAfter the study drug treatment blind is broken in study EN3835-302/303 and subjects have been classified based on Day 71 composite responses in study 
EN3835-302/303, Category I and Category II subjects that qualify for treatment may elect to receive one and only one course of EN3835 retreatment 
(ie, 3 treatment sessions) in up to 2 buttocks. If a subject does not qualify  for treatment at that time, she may undergo another Screening B at a later time, if still 
eligible for treatment. 
c Upon completion of treatment, subjects will be followed at intervals as described in Section 5.3; if the 71-day treatment period overlaps with an Observation 
Visit in Section 5.3 for a subject, that particular Observation visit will be skipped and the subject will be assessed at the next scheduled Observation Visit in 
Section 5.3. 
d Informed consent for Category I and eligible Category II subjects who opt to receive retreatment. 
e Photographs of both left and right buttocks should be taken. 
f Before and after marking dimples and injection sites. 
g Including XIAFLEX as a concomitant medication; the use of the word ‘prior’ refers to the period between the last visit from the previous Phase 3 clinical study 
through the signing of informed consent in the EN3835-304 study; not applicable to subjects who sign consent for this study on the same day that they 
complete the EN3835-302/303 study. 
h Before injection. 
i Up to 4 hours before injection; approximately 15 and 30 minutes after injection. Pulse and blood pressure to be taken after subject has been sitting for 
5 minutes. Vital signs must be stable before the subject is discharged. Refer to Section 14.9. 
j Do not conduct if Screening B visit date is within 12 months of obtaining an ECG during the double-blind study (EN3835-302/303). 
k Serum pregnancy test occurs at  Screening Visit and Day 71/EOS visit; urine pregnancy test on Day 1, Day 22, and Day 43 Visits and Unscheduled Visit. 
l Assessment made via photographs (if treatment visit, use photographs taken before marking dimples and injection sites).  
,mSubject assessments should be completed independently and prior to investigator assessments at each visit. Includes both buttocks regardless of treatment, each 
buttock should be assessed independently. 
n At least one of the Category I subject’s buttocks must have scores/ratings of at least 2 in both the CR-PCSS and PR-PCSS to be eligible to receive treatment. 
Category II subjects must have at least a 1-level composite response reduction compared to Day 71 of the EN3835-302/303 study AND no longer maintain a 
2-level composite response compared to baseline in the EN3835-302/303 study on either or both buttocks.  

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o Local adverse events associated with the injection site, including acute (eg, erythema, bruising, pain, nodules/mass, ulceration, blistering, pruritus, swelling, 
and/or induration) and/or chronic (eg, skin thickening, fibrosclerosis, peau d’orange changes) cutaneous adverse events, will be recorded and evaluated for 
seriousness and severity. 
 ECG=Electrocardiogram; EFP=Edematous fibrosclerotic panniculopathy; EOS=End of study; Tx=Treatment. 

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5.3. 
Category I/II Subjects – Observation Assessments 
Proceduresa 
OBS Visit 2 
Day 360 
(±30 d) 
(M12) 
OBS Visit 3 
Day 540 
(±30 d) 
(M18) 
OBS Visit 4 
Day 720 
(±30 d) 
(M24) 
OBS Visit 5 
Day 
1080/EOS/ 
Early 
Termination 
(±30 d) (M36) 
Durability 
Confirmation 
Visitb  
Verification of informed consent 
X 
 
 
 
 
Inclusion/exclusion 
X 
 
 
 
 
Digital photography 
X 
X 
X 
X 
X 
Prior/concomitant medications/proceduresc 
X 
X 
X 
X 
 
Anti-AUX-I/anti-AUX-II antibody level 
X 
X 
X 
X 
 
Subject Cellulite Assessments 
 
 
 
 
 
• Review assessments’ training and use materials 
X 
X 
X 
X 
X 
• Patient Reported Photonumeric Cellulite Severity Scale (PR-
PCSS)d,e  
X 
X 
X 
X 
X 
• Subject Global Aesthetic Improvement Scale (S-GAIS)d 
X 
X 
X 
X 
 
• Patient Reported Cellulite Impact Scale (PR-CIS)d 
X 
X 
X 
X 
 
• Subject Satisfaction With Cellulite Treatment Assessmentd 
X 
X 
X 
X 
 
• Subject Self-Rating Scale (SSRS) 
X 
X 
X 
X 
 
Investigator Cellulite Assessments 
 
 
 
 
 
• Review assessment’s training and use materials 
X 
X 
X 
X 
X 
• Clinician Reported Photonumeric Cellulite Severity Scale (CR-
PCSS)e 
X 
X 
X 
X 
X 
Local safety assessmentsf  
X 
X 
X 
X 
X 
Adverse events 
Monitored throughout study 

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a Unscheduled visits may be done as deemed necessary at any time during the study to ensure subject safety; assessments done at unscheduled visits are at the 
discretion of the investigator. No photographs or cellulite severity assessments will be done at unscheduled visits. 
b If the composite (CR-PCSS and PR-PCSS) ratings worsen by at least 1-level composite response ratings for a subject, an additional visit should be scheduled 
14 days (± 5 days) later to confirm reduction of response, via re-assessment with the CR-PCSS and PR-PCSS. If reduction of response is confirmed, subjects 
will be offered one course of retreatment (one and only one course of retreatment in up to 2 buttocks concurrently will be offered to an individual subject 
during this open-label study from Visit 1 to Visit 5 (approximately 6 to 36 months after Day 71 of the double-blind study, respectively). The Sponsor has 
decided to terminate the EN3835-304 clinical trial at the completion of 3-year time point (Day 1080) and will offer voucher(s) for commercially approved Qwo 
redeemable only for those trial participant(s) who will miss their potential retreatment opportunity due to this decision. Retreatment will only be offered 
following confirmation of eligibility through cellulite assessments performed at the Day 1080 visit for those participants, and a confirmation visit (as 
applicable).  
c Including XIAFLEX as a concomitant medication; the use of the word ‘prior’ refers to the period between the last visit from the previous Phase 3 clinical study 
through the signing of informed consent in the EN3835-304 study; not applicable to subjects who sign consent for this study on the same day that they 
complete the EN3835-302/303 study. 
d Assessment made via photographs.  
e Subject assessments should be completed independently and prior to Investigator assessments at each visit. Assessment of each of the 2 buttocks is to be made 
independently. 
f Local adverse events associated with the injection site, including acute (eg, erythema, bruising, pain, nodules/mass, ulceration, blistering, pruritus, swelling, 
and/or induration) and/or chronic (eg, skin thickening, fibrosclerosis, peau d’orange changes) cutaneous adverse events, will be recorded and evaluated for 
seriousness and severity. 
d=Days; EFP=Edematous fibrosclerotic panniculopathy; EOS=End of study; M=Month(s); OBS=Observation. 
 

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5.4. 
Category III Subjects - Assessments 
Proceduresa 
OBS Visit 2 
Day 360 
(±30 d)  
(M12) 
OBS Visit 3 
Day 540 
(±30 d)  
(M18) 
OBS Visit 4 
Day 720 
(±30 d)  
(M24) 
OBS Visit 5 
Day 1080 EOS/Early 
Termination 
(±30 d)  
(M36) 
Verification of informed consent 
X 
 
 
 
Inclusion/exclusion 
X 
 
 
 
Prior/concomitant medications/proceduresb  
X 
X 
X 
X 
• Anti-AUX-I/anti-AUX-II antibody level 
X 
X 
X 
X 
Local safety assessmentsc 
X 
X 
X 
X 
Adverse events 
Monitored throughout study 
a Unscheduled visits may be done as deemed necessary at any time during the study to ensure subject safety; assessments done at unscheduled visits are at the 
discretion of the investigator. No photographs or cellulite severity assessments will be done at unscheduled visits. 
b Including XIAFLEX as a concomitant medication; the use of the word ‘prior’ refers to the period between the last visit from the previous Phase 3 clinical study 
through the signing of informed consent in the EN3835-304 study; not applicable to subjects who sign consent for this study on the same day that they 
complete the EN3835-302/303 study. 
c Local adverse events associated with the injection site from the 302/303 studies, including acute (eg, erythema, bruising, pain, nodules/mass, ulceration, 
blistering, pruritus, swelling, and/or induration) and/or chronic (eg, skin thickening, fibrosclerosis, peau d’orange changes) cutaneous adverse events, will be 
recorded and evaluated for seriousness and severity. 
d=Days; EOS=End of study; M=Month; OBS=Observation

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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 
2.1. 
Amendment 3 ................................................................................................................2 
2.2. 
Amendment 2 ................................................................................................................3 
2.3. 
Amendment 1 ................................................................................................................9 
3. 
SPONSOR CONTACT INFORMATION .................................................................60 
4. 
SYNOPSIS .................................................................................................................61 
5. 
SCHEDULE OF EVENTS .........................................................................................66 
5.1. 
Up to 180 Days ...........................................................................................................66 
5.2. 
Eligible Category I/II Subjects – Treatment Session Assessments ............................68 
5.3. 
Category I/II Subjects – Observation Assessments ....................................................71 
5.4. 
Category III Subjects - Assessments ..........................................................................73 
6. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............74 
TABLE OF CONTENTS ...............................................................................................................74 
LIST OF TABLES .........................................................................................................................79 
LIST OF FIGURES .......................................................................................................................79 
7. 
LIST OF ABBREVIATIONS .....................................................................................81 
8. 
INTRODUCTION ......................................................................................................82 
8.1. 
Background .................................................................................................................82 
8.1.1. 
Edematous Fibrosclerotic Panniculopathy .................................................................82 
8.1.2. 
Current EFP Treatments .............................................................................................82 
8.1.3. 
EN3835 (Collagenase Clostridium Histolyticum) ......................................................83 
8.2. 
Summary of Nonclinical Studies ................................................................................84 
8.3. 
Summary of Known Risks and Benefits .....................................................................84 
8.4. 
Rationale .....................................................................................................................85 
9. 
OBJECTIVES .............................................................................................................86 
9.1. 
Primary Objective .......................................................................................................86 
9.2. 
Secondary Objectives .................................................................................................86 
9.3. 
Exploratory Objectives ...............................................................................................86 

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10. 
INVESTIGATIONAL PLAN .....................................................................................87 
10.1. 
Study Design ...............................................................................................................87 
10.2. 
Selection of Doses ......................................................................................................90 
10.3. 
Study Drug Administration (Eligible Category I and Category II Subjects) ..............90 
10.4. 
Care Procedures After Injection .................................................................................92 
10.5. 
Discussion of Study Design, Including the Choice of Control Groups ......................92 
11. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................93 
11.1. 
Subject Inclusion Criteria ...........................................................................................93 
11.1.1. 
Inclusion Criteria - All Subjects (Through Day 180) .................................................93 
11.1.2. 
Inclusion Criteria - Category I Subjects (Post Unblinding of 
EN3835-302/303) .......................................................................................................93 
11.1.3. 
Inclusion Criteria - Category II Subjects (Post Unblinding of 
EN3835-302/303) .......................................................................................................94 
11.1.4. 
Inclusion Criteria - Category III Subjects (Post Unblinding of 
EN3835-302/303) .......................................................................................................94 
11.1.5. 
Inclusion Criteria - Category I and Category II Subjects Who Opt for 
Retreatment (Post Unblinding of EN3835-302/303) ..................................................94 
11.2. 
Subject Exclusion Criteria ..........................................................................................95 
11.2.1. 
Exclusion Criteria - All Subjects (Through Day 180) ................................................95 
11.2.2. 
Exclusion Criteria - Category I and Category II Subjects (Post Unblinding of 
EN3835-302/303) .......................................................................................................96 
11.2.3. 
Exclusion Criteria - Category III Subjects (Post Unblinding of 
EN3835-302/303) .......................................................................................................96 
11.2.4. 
Exclusion Criteria Category I and II Subjects Who Opt to Receive 
Retreatment (Post Unblinding of EN3835-302/303) ..................................................96 
11.3. 
Subject Discontinuation Criteria .................................................................................97 
11.3.1. 
Replacement Procedures .............................................................................................98 
12. 
TREATMENT OF SUBJECTS ..................................................................................99 
12.1. 
Study Visits .................................................................................................................99 
12.1.1. 
Informed Consent .......................................................................................................99 
12.1.2. 
Subject Screening Screening A/ Day 71 Visit of Double-blind Study 
(± 14 Days) .................................................................................................................99 
12.1.3. 
Medical History ..........................................................................................................99 
12.1.4. 
Study Entry/Observational Assessments (Up to Day 180) .......................................100 
12.1.5. 
Day 180/Early Termination Visit/Screening B .........................................................100 

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12.2. 
Category I Subjects and Category II Subjects Visits (Post Unblinding of 
EN3835-302/303) .....................................................................................................101 
12.2.1. 
Treatment Assessments (Treatment is Optional for Eligible Subjects) ....................102 
12.2.1.1. 
Screening B (Days -14 to -1 Relative to Treatment Visit 1) ....................................102 
12.2.1.2. 
Selecting and Marking Dimples During Treatment Visits .......................................103 
12.2.1.3. 
Digital Photography during Treatment Visits 1, 2, and 3 .........................................104 
12.2.1.4. 
Treatment Visit 1 ......................................................................................................104 
12.2.1.5. 
Treatment Visits 2 and 3 (Day 22 ± 3 days and Day 43 ± 3 days) ...........................105 
12.2.1.6. 
Treatment Visit 4 (Day 71 + 5 days) ........................................................................106 
12.2.2. 
Observation Assessments .........................................................................................107 
12.2.2.1. 
Observation Visit 2 (Day 360 Relative to Day 71 of the Double-blind Study) ........107 
12.2.2.2. 
Observation Visits 3-5/EOS/Early Termination (Day 540 – 
Day 1080/EOS/Early Termination) ..........................................................................108 
12.2.2.3. 
Confirmation Visits ..................................................................................................109 
12.3. 
Category III Subjects Visits (Post Unblinding of EN3835-302/303) .......................110 
12.3.1. 
Observation Visits 2-5/EOS/Early Termination (Day 360 – 
Day 1080/EOS/Early Termination) ..........................................................................110 
12.4. 
Unscheduled Visit .....................................................................................................110 
12.5. 
Prior and Concomitant Medications and Procedures ................................................110 
12.5.1. 
Prohibited Medications or Procedures ......................................................................111 
12.6. 
Treatment Compliance ..............................................................................................111 
13. 
ASSESSMENT OF EFFICACY ..............................................................................112 
13.1. 
Efficacy Measurements ............................................................................................112 
13.1.1. 
Digital Photography ..................................................................................................112 
13.1.2. 
Subject and Investigator Cellulite Assessments .......................................................112 
13.1.2.1. 
Patient Reported Photonumeric Cellulite Severity Scale (PR-PCSS) ......................112 
13.1.2.2. 
Subject Global Aesthetic Improvement Scale (S-GAIS) ..........................................113 
13.1.2.3. 
Patient Reported Cellulite Impact Scale (PR-CIS) ...................................................114 
13.1.2.4. 
Subject Satisfaction with Cellulite Treatment Assessment ......................................114 
13.1.2.5. 
Subject Self-Rating Scale (SSRS) ............................................................................114 
13.1.2.6. 
Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) ..................115 
14. 
ASSESSMENT OF SAFETY ...................................................................................116 
14.1. 
Definitions ................................................................................................................116 

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14.1.1. 
Adverse Events .........................................................................................................116 
14.1.2. 
Serious Adverse Events ............................................................................................116 
14.2. 
Monitoring Adverse Events ......................................................................................117 
14.3. 
Relationship to Study Drug ......................................................................................117 
14.4. 
Intensity Assessment ................................................................................................118 
14.5. 
Reporting Adverse Events and Serious Adverse Events ..........................................118 
14.5.1. 
Reporting Adverse Events ........................................................................................118 
14.5.2. 
Reporting Serious Adverse Events ...........................................................................118 
14.5.2.1. 
Follow-up Procedures for Serious Adverse Events ..................................................119 
14.6. 
Special Reporting Situations .....................................................................................119 
14.6.1. 
Adverse Events of Special Interest ...........................................................................119 
14.6.2. 
Overdose/Misuse/Abuse ...........................................................................................119 
14.6.2.1. 
Overdose ...................................................................................................................119 
14.6.3. 
Pregnancy .................................................................................................................120 
14.6.4. 
AEs/SAEs Experienced by Non-subjects Exposed to Study Medication .................120 
14.7. 
Clinical Laboratory Determinations .........................................................................121 
14.8. 
Anti-AUX-I and Anti-AUX-II Antibodies ...............................................................122 
14.9. 
Vital Signs ................................................................................................................123 
14.10. 
Electrocardiogram .....................................................................................................123 
14.11. 
Physical Examination ...............................................................................................123 
14.12. 
Other Safety Assessments .........................................................................................124 
15. 
ASSESSMENT OF PHARMACOKINETICS .........................................................125 
16. 
ASSESSMENT OF PHARMACODYNAMICS ......................................................126 
17. 
STATISTICAL CONSIDERATIONS AND METHODS .......................................127 
17.1. 
Determination of Sample Size ..................................................................................127 
17.2. 
Subject Populations ..................................................................................................127 
17.2.1. 
Overall Safety Population .........................................................................................127 
17.2.2. 
Day 180 Observational Population ...........................................................................127 
17.2.3. 
Time to Reduction of Response (TRR) Population ..................................................127 
17.3. 
Subject Disposition ...................................................................................................127 
17.4. 
Demographics and Other Baseline Characteristics ...................................................128 
17.5. 
Efficacy Analyses .....................................................................................................128 
17.5.1. 
Analyses ....................................................................................................................128 

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17.6. 
Safety Analyses ........................................................................................................129 
17.6.1. 
Prior, Concomitant, and Follow-up Medication .......................................................129 
17.6.2. 
Study Drug Exposure ................................................................................................130 
17.6.3. 
Adverse Events .........................................................................................................130 
17.6.4. 
Vital Signs ................................................................................................................130 
17.6.5. 
Clinical Laboratory Parameters ................................................................................130 
17.7. 
Immunogenicity Analyses ........................................................................................130 
17.8. 
Pharmacokinetic Analyses ........................................................................................131 
17.9. 
Pharmacodynamic Analyses .....................................................................................131 
17.10. 
Other Data (eg, Health Economics/QOL, Pharmacogenetic, etc) ............................131 
17.11. 
Interim Analysis ........................................................................................................131 
17.12. 
Statistical Software ...................................................................................................131 
18. 
STUDY DRUG MATERIALS AND MANAGEMENT .........................................132 
18.1. 
Study Drug Identity ..................................................................................................132 
18.2. 
Study Drug Packaging and Labeling ........................................................................132 
18.3. 
Study Drug Storage ...................................................................................................132 
18.4. 
Study Drug Preparation ............................................................................................132 
18.5. 
Study Drug Accountability .......................................................................................133 
18.5.1. 
Study Drug Handling and Disposal ..........................................................................133 
19. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS .......................................134 
19.1. 
Source Documents ....................................................................................................134 
19.2. 
Study Monitoring ......................................................................................................134 
19.3. 
Audits and Inspections ..............................................................................................134 
19.4. 
Institutional Review Board (IRB) .............................................................................134 
19.5. 
Data Recording and Documentation .........................................................................134 
20. 
QUALITY CONTROL AND QUALITY ASSURANCE .......................................135 
21. 
ETHICS ....................................................................................................................136 
21.1. 
Ethics Review ...........................................................................................................136 
21.2. 
Ethical Conduct of the Study ....................................................................................136 
21.3. 
Subject Information and Consent .............................................................................136 
22. 
DATA HANDLING AND RECORDKEEPING .....................................................138 
22.1. 
Data Collection .........................................................................................................138 
22.2. 
Study Documentation ...............................................................................................138 

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23. 
REPORTING AND PUBLICATION .......................................................................139 
24. 
INVESTIGATOR OBLIGATIONS .........................................................................139 
24.1. 
Regulatory Documents .............................................................................................139 
24.2. 
Delegation of Responsibilities and Adequate Resources .........................................140 
24.3. 
Medical Care of Study Subjects ...............................................................................140 
24.4. 
Use of Investigational Materials ...............................................................................140 
24.5. 
Retention of Records ................................................................................................140 
24.6. 
Subject Confidentiality .............................................................................................141 
25. 
TERMINATION OF STUDY ..................................................................................142 
26. 
INVESTIGATOR’S STATEMENT .........................................................................143 
27. 
REFERENCES .........................................................................................................144 
APPENDIX A. DOCUMENTS REQUIRED PRIOR TO INITIATION OF THE 
STUDY ............................................................................................................145 
APPENDIX B. PATIENT REPORTED PHOTONUMERIC CELLULITE SEVERITY 
SCALE (PR-PCSS) FOR THE BUTTOCK ....................................................147 
APPENDIX C. CLINICIAN REPORTED PHOTONUMERIC CELLULITE 
SEVERITY SCALE (CR-PCSS) FOR THE BUTTOCK ...............................148 
APPENDIX D. PATIENT REPORTED CELLULITE IMPACT SCALE (PR-CIS) ..............149 
 
LIST OF TABLES 
Table 1: 
Sponsor Contact Information ......................................................................................60 
Table 2: 
Abbreviations ..............................................................................................................81 
Table 3: 
Study Retreatment (Eligible Category I and Category II Subjects Only) ..................90 
Table 4: 
Concomitant Medication Restrictions for Category I and Category II 
Subjects During the Retreatment Phase of Study (Treatment Visits 1 - 4) ..............111 
Table 5: 
Subject Global Aesthetic Improvement Scale (S-GAIS) ..........................................113 
Table 6: 
Subject Satisfaction with Cellulite Treatment Assessment - Buttocks .....................114 
Table 7: 
Subject Self-Rating Scale (SSRS) ............................................................................115 
Table 8: 
Clinical Laboratory Tests .........................................................................................122 
Table 9: 
Vital Signs Measurements on Injection Day ............................................................123 
 
LIST OF FIGURES 
Figure 1: 
Study Design ...............................................................................................................89 

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Figure 2: 
Study Drug Administration at Each Injection Site .....................................................91 
 

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7. 
LIST OF ABBREVIATIONS  
The following abbreviations are used in this study protocol. 
Table 2: 
Abbreviations  
Abbreviation 
Definition 
AE 
Adverse event 
AUX-I 
Clostridial class I collagenase 
AUX-II 
Clostridial class II collagenase 
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 
IWRS 
Interactive web response system 
PR-CIS 
Patient Reported Cellulite Impact Scale 
PR-PCSS 
Patient Reported Photonumeric Cellulite Severity Scale 
SAE 
Serious adverse event 
S-GAIS 
Subject Global Aesthetic Improvement Scale 
SSRS 
Subject Self-Rating Scale 
TEAE 
Treatment-emergent adverse event 
TRR 
Time to reduction of response 

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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- 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, and 
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 
discoloration (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. For a comprehensive review of relevant safety information, please refer to the 
Investigator Brochure. 
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 
of the use of EN3835 in the treatment of EFP. 
Studies EN3835-302 and EN3835-303 are both phase 3, double-blind, placebo-controlled, 
multi-center studies designed to assess the safety and efficacy of EN3835 for the treatment of 
EFP in the buttocks. In each study, eligible subjects will have both buttocks treated with EN3835 
or placebo, and will be assessed for cellulite severity for 71 days. After subjects complete the 
double-blind study, subjects who received active EN3835 in the double-blind studies will roll 
over into the current long-term study for continued safety assessments (including 
immunogenicity profile) and efficacy assessments where applicable for up to 3 years. In 
addition, subjects who showed only a 1-level composite improvement in cellulite severity in the 
double-blind studies will be eligible for an additional open-label treatment course in the 
open-label study. The retreatment course for eligible subjects will follow the same regimen as 
previous studies, utilizing 0.84 mg per treatment area.  

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9. 
OBJECTIVES 
9.1. 
Primary Objective 
The primary objectives of this study are to assess: 
• the long-term safety of EN3835 in the treatment of edematous fibrosclerotic 
panniculopathy (EFP) commonly known as cellulite in adult women 
• the safety of EN3835 when used for retreatment in the treatment of EFP commonly 
known as cellulite in adult women 
• the long-term immunogenicity profile of EN3835 following treatment of EFP 
commonly known as cellulite in adult women 
9.2. 
Secondary Objectives 
The secondary objective of this study is to assess the time to reduction of response (TRR) to 
EN3835 in the treatment of EFP in adult women. 
9.3. 
Exploratory Objectives 
There are no exploratory objectives of this study. 
 

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10. 
INVESTIGATIONAL PLAN 
10.1. 
Study Design 
This open-label extension study will be performed at multiple centers currently participating in 
the double-blind, placebo-controlled, parent trials (EN3835-302/EN3835-303) in the United 
States. The open-label extension study will initially enroll up to 840 subjects until the 
double-blind studies are unblinded, after which only subjects who received active EN3835 will 
remain in observation in the current study. Subjects who completed the double-blind study and 
sign an informed consent will be eligible to enter this open-label extension.  
Following completion of safety and cellulite assessments (at least Patient Reported Photonumeric 
Cellulite Severity Scale [PR-PCSS] and the Clinician Reported Photonumeric Cellulite Severity Scale 
[CR-PCSS]) at Day 71 of the double-blind study (EN3835-302/303), subjects will be asked to 
continue in the open-label extension to the double-blind study (ie, EN3835-304, the current 
study). Assessments made at Day 71/EOS of the double-blind study will serve as initial 
screening for the current open-label extension study. At the time of entry into the open-label 
study and at Visit 1 at Day 180 of study EN3835-304 (approximately 6 months after Day 71 of 
study EN3835-302/303), subjects and Investigators and site personnel will remain blinded to 
study drug treatment received in the double-blind study. Even if the EN3835-302/303 study drug 
blind is broken by the Sponsor; subjects, Investigators and site personnel in study EN3835-304 
will remain blinded until after Day 180 safety and cellulite severity assessments of each 
treatment area are completed. Upon completion and unblinding of the double-blind studies 
EN3835-302/303 (which may occur immediately after Day 180 Visit assessments are completed 
if the study drug blind has been broken by Sponsor, or may occur during a visit (Unscheduled 
Visit) after the Day 180 Visit if the blind is not broken by Sponsor until sometime after Day 
180), subjects who received placebo during the double-blind studies will be discontinued, and 
subjects who received active EN3835 will be classified into one of three categories: 
Category I: 
1-Level Composite Responders 
Category II: 
2-Level Composite Responders 
Category III: Non-Composite Responders 
Category I will include subjects in which the maximum composite response in either (or both) 
buttock(s) in EN3835-302 or EN3835-303 was ONLY a 1-level composite improvement in 
cellulite severity as assessed by the PR-PCSS and the CR-PCSS. In cases where there is an 
improvement in both buttocks, the composite improvement of one level must have occurred in 
the same buttock to be eligible (ie, the PR-PCSS and CR-PCSS improvement must have been in 
the same buttock). Subjects showing a 2-level improvement in one scale but only a 1-level 
improvement in the other scale are also considered Category I subjects, provided the composite 
improvement is within the same buttock. Category I subjects will be eligible for one additional 
retreatment course in up to two buttocks in the current open-label study. Retreatment may begin 
on Day 180 if the study drug blind from the double-blind study (EN3835-302/303) has been 
broken. Only buttocks with a composite 1-level improvement or less will be retreated. 
Assessment of open-label efficacy following retreatment will be determined up to Treatment 
Visit 4 (Day 71 + 5 days), after which subjects will be observed, depending when during the 
3-year period the subject receives retreatment, every 6 months for 2 years and then annually for 

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up to 3 years (Day 1080) after Day 71 of study EN3835-302/303. Eligible subjects who qualify 
for Category I status who choose NOT to receive additional retreatment will have observation 
visits (Visits 2-5) as detailed in Section 5.3.  
Category II will include subjects who showed an improvement in cellulite severity of at least 2 
levels in at least one buttock in both the PR-PCSS and the CR-PCSS (ie, 2-level composite 
responder) in EN3835-302 or EN3835-303. These subjects will be observed for TRR (defined 
below) and safety approximately every 6 months for 2 years and will be observed annually for up 
to 3 years (Day 1080) from Day 71 of the double-blind studies. Category II subjects must have at 
least a 1-level composite response reduction compared to Day 71 of the EN3835-302/303 study 
AND no longer maintain a 2-level composite response compared to baseline in the 
EN3835-302/303 study on either or both buttocks to be eligible for retreatment as detailed in 
Section 5.2; after which they will be observed at observation visits as detailed in Section 5.3.  
Category I and Category II subjects who participate in the observational phase of the study, will 
have cellulite assessments completed during the observational visits at Months 12, 18, 24, and 
36. At Months 12, 18, 24, and 36,  if the ratings indicate that the buttock(s) is eligible for 
retreatments and the subject has not received EN3835 previously in study EN3835-304, the 
subject will be offered one course of treatment for the eligible buttock(s); one course of 
concurrent treatment for up to two eligible buttocks.  
Category III subjects will include all other subjects who received active EN3835 in study 
EN3835-302 or EN3835-303 but did not meet criteria to be included in Category I or II 
(ie, noncomposite responders). These subjects will be observed for safety every 6 months for 
2 years and annually for up to 3 years (Day 1080) as detailed in Section 5.4, and will not be 
eligible for retreatment during the study. 
The retreatment course for eligible Category I and Category II subjects will consist of 3 
treatment sessions separated by 21 days. Each retreatment session will consist of 12 injections 
(0.07 mg/0.3 mL per injection) of EN3835 for a dose of 0.84 mg and volume of 3.6 mL 
(identical to the treatment course administered in the double-blind study), in each qualifying 
buttock (Table 3) in up to two buttocks treated concurrently. One and only one retreatment 
course in up to 2 qualifying buttocks concurrently will be offered to eligible Category I and 
Category II subjects during this 3 year study. After initiation of retreatment (on Treatment 
Visit 1; Treatment Day 1), subjects will be assessed for safety on each day of injection during 
retreatment, and assessed for safety and cellulite severity on Treatment Visit 2 (Day 22), 
Treatment Visit 3 (Day 43) and Treatment Visit 4 (Day 71). 
For study purposes; reduction of response (ie, lessening of response or loss of response) is 
defined as a 1-level composite worsening of cellulite severity improvement observed at Day 71 
of the double-blind studies (EN3835-302/303) on both the PR-PCSS and CR-PCSS. TRR is 
defined as the time from assessing efficacy (Day 71 of double-blind study) to the study visit at 
which a composite 1-level loss of response in both PR-PCSS and CR-PCSS is observed. 
Durability of response is defined as a complete loss of response in which cellulite severity 
returns back to baseline levels (on both the PR-PCSS and CR-PCSS on Day 1 of the double-
blind studies). Confirmation of reduction of response and/or complete loss of response will be 
established during a follow-up visit ~2 weeks after a composite reduction of response is first 
detected. 

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Once enrolled in the current open-label study, subjects will again receive instructions for use of 
the PR-PCSS and will subsequently use the scale to rate the severity of their cellulite in each of 
the treatment areas on a standardized computer monitor with the PR-PCSS instrument. This 
independent self-assessment will take place in a private setting to minimize any potential bias 
from site personnel. The Investigator will then assess the subject’s treatment areas live in 
real-time using the CR-PCSS. Both the Investigator and the subject will remain blinded to each 
other’s assessments for the duration of the open-label study, even after the study drug treatment 
blind is broken for each double-blind study by the Sponsor. Throughout the study, subjects and 
Investigators will be provided training materials and will refresh on training prior to the use of 
each cellulite assessment at each visit. 
The Schedule of Events for all subjects up through 180 days following studies EN3835-302/303 
is provided in Section 5.1. Beyond Day 180, the Schedule of Events for subjects classified as 
categories I and II and who are eligible and opt to receive retreatment is provided in Section 5.2 
and in observational phase of study Section 5.3. The Schedule of Events for subjects in 
Category I or Category II who are not eligible for retreatment, or are in Category I and II and 
who are eligible but opt not to have retreatment, is provided in Section 5.3. The Schedule of 
Events for Category III subjects is shown in Section 5.4.  
Figure 1: 
Study Design 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 

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Table 3: 
Study Retreatment (Eligible Category I and Category II Subjects Only) 
Dose per 
Each Injection a 
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 
0.3 mL 
12 per buttock  
× up to 2 buttocks = 
up to 
24 injections 
0.84 mg per buttock  
× up to 2 buttocks = 
1.68 mg 
(12 injections  
per buttock ×  
0.07 mg/injection ×  
up to 2 buttocks) 
3.6 mL per buttock  
× up to 2 buttocks = 
up to 7.2 mL  
(24 injections × 
0.3 mL) 
5.04 mg 
(3 treatment visits × 
0.84 mg per buttock 
× up to 2 buttocks) 
a Each injection of study drug is 0.3 mL administered as three 0.1 mL aliquots. 
10.2. 
Selection of Doses 
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 the parent double-blind studies 
EN3835-302/303, and to this open-label extension study in subjects getting retreatment. The 
findings from previous studies that the majority of adverse events (AEs) after EN3835 treatment 
are local to the injection site and that there is no quantifiable systemic exposure observed after 
concurrent treatment of two buttocks (0.84 mg/buttock; total dose of 1.68 mg) supports the 
proposed dose to evaluate EN3835 in treatment of one or both buttocks. 
For a complete history of prior investigations related to the selection of dose used in the current 
study, refer to the IB.(11) 
10.3. 
Study Drug Administration (Eligible Category I and Category II 
Subjects) 
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 Figure 2. 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 retreatment visit, 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 injections 
of 0.3 mL per injection will be administered within each buttock getting retreated during each 
treatment visit. 

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Figure 2: 
Study Drug Administration at Each Injection Site 
 
• Needle Tip Position A: Position the needle at 90° angle perpendicular to the skin 
surface at the injection site and inject one 0.1-mL aliquot of study drug by gently 
pushing on the syringe plunger. 
• Needle Tip Position B: Withdraw the needle slightly (but not so much as to remove 
from the injection site) and reposition approximately 45° (but not more than 45°) off 
vertical and above the long axis of the dimple and inject one 0.1-mL aliquot of study 
drug) by gently pushing on the syringe plunger. Position B should be towards the 
head (cephalad) of the subject. 
• Needle Tip Position C: Withdraw the needle slightly (but not so much as to remove 
from the injection site) and reposition approximately 45° (but not more than 45°) off 
vertical and below the long axis of the dimple and inject one 0.1-mL aliquot of study 
drug by gently pushing on the syringe plunger. Position C should be towards the feet 
(caudal) of the subject. 
• Withdraw needle from the skin completely and move to the next identified injection 
site. Complete a total of three 0.3-mL injections (each administered as three 0.1 mL 
aliquots) and discard the first syringe appropriately. Use the second, third and fourth 
syringes to complete dosing in each buttock (three 0.3-mL injections per syringe, 
each injection administered as three 0.1-mL aliquots). Twelve (12) skin injections of 
0.3 mL will be administered within each of the two treated buttocks during each 
treatment visit. 
• The plane containing injection deposition points A, B, and C should be perpendicular 
to the skin and perpendicular to the long axis of a dimple if the dimple is an elongated 
trough-like dimple. In most cases, the plane containing injection points A, B, and C 
will be parallel to the long axis of the subject’s body. 
• After treatment the subject will remain prone for at least 5 minutes. 
The total number of dimples treated and the total number of injections administered will be 
recorded during Treatment Visits 1, 2, and 3.  
0.1 mL 
0.1 mL 
0.1 mL
 
 
 
 
 
 
 
 
 
 

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NOTE: EN3835 is a foreign protein and Investigators must 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, and 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 
This study is a long-term follow-up study of subjects who received EN3835 0.84 mg per buttock 
in the concurrent treatment (total dose of up to 1.68 mg) of 2 bilateral buttocks with EFP in adult 
women in a 71-day double-blind, placebo-controlled study (EN3835-302 or EN3835-303). After 
completion in one of the aforementioned studies, subjects will be followed for up to 3 years from 
the Day 71 of the double-blind study (EN3835-302/303), which is approximately 28 days after 
the last exposure of EN3835 in study EN3835-302/303. Study EN3835-304 is being conducted 
as a multi-center, open-label extension study. The use of the open-label extension design allows 
for the following: 
• Safety data over the course of up to 3 years (1080 days following Day 71 of 
double-blind) will be collected to assist in further defining the safety profile of 
EN3835 in this population, 
• Safety data, immunogenicity, and responsiveness after repeat exposure (retreatment) 
and monitoring of previously EN3835 treated subjects for up to 3 years (1080 days 
following Day 71 of double-blind),  
• Safety data, immunogenicity and responsiveness after repeat exposure (retreatment) 
in subjects that show a reduction from the improvement observed at Day 71 of the 
double-blind studies and 
• Time to reduction in the response to EN3835 using cellulite severity assessments will 
be evaluated at various time points. 

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11. 
SELECTION AND WITHDRAWAL OF SUBJECTS  
11.1. 
Subject Inclusion Criteria 
11.1.1. 
Inclusion Criteria - All Subjects (Through Day 180) 
In order to be eligible to participate in the study, subjects must: 
1. Voluntarily sign and date an informed consent agreement. 
2. Have participated in and completed the double-blind Phase 3 study EN3835-302 or 
EN3835 303 (ie, assessed safety and obtained PR-PCSS and CR-PCSS ratings at 
Day 71/EOS of the double-blind study; does not include early termination subjects). 
3. Be willing to apply sunscreen to both buttocks before each exposure to the sun and/or 
tanning booths while participating in the study during this period. 
4. Be judged to be in good health, based upon the results of a physical examination and 
laboratory profile at Screening.  
5. Be willing and able to cooperate with the requirements of the study. 
6. Be able to read, complete and understand the patient reported outcomes rating 
instruments in English. 
NOTE: After Day 180 Visit assessments are completed in study EN3835-304 and unblinding of 
EN3835-302/303, subjects who received EN3835 in EN3835-302 or EN3835-303 will be placed 
into one of three categories based on their responder status of each of their buttocks at Day 71 in 
study EN3835-302 or EN3835-303 (Section 10.1). Investigators, subjects and all site personnel 
will be blinded to the treatment that the subjects received in the double-blind studies until 
assessments at the Day 180 visit of study EN3835-304 are completed; even if this visit occurs 
after the EN3835-302/303 studies are unblinded by Endo. Investigator, subjects, and site 
personnel will be unblinded on Day 180 of study EN3835-304 after Day 180 assessments are 
completed or at an Unscheduled Visit, pending when database lock and unblinding of studies 
EN3835-302/303 occurs relative to Day 180 of this current study EN3835-304. The following 
additional inclusion criteria will apply after Day 180 to subjects in Categories I, II, and III as 
well as to subjects in Categories I and II who opt to be retreated. 
11.1.2. 
Inclusion Criteria - Category I Subjects (Post Unblinding of EN3835-302/303) 
In order for Category I subjects to continue to participate in this study, subjects must: 
1. Voluntarily sign and date an informed consent agreement. 
2. Have received active EN3835 in study EN3835-302 or EN3835-303. 
3. Have had a maximum composite response at Day 71 in either or both buttocks in double-
blind study EN3835-302 or EN3835-303 that was ONLY a 1-level improvement on 
CR-PCSS/PR-PCSS. 
4. Be willing to apply sunscreen to the buttocks before each exposure to the sun. 
5. Be judged to be in good health, based upon the results of a physical examination and 
laboratory profile at Screening.  

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6. Be willing and able to cooperate with the requirements of the study. 
7. Be able to read, complete and understand the patient reported outcomes rating 
instruments in English. 
11.1.3. 
Inclusion Criteria - Category II Subjects (Post Unblinding of EN3835-302/303) 
In order for Category II subjects to continue to participate in this study, subjects must: 
1. Voluntarily sign and date an informed consent agreement. 
2. Have received active EN3835 in study EN3835-302 or EN3835-303. 
3. Have had a composite response at Day 71 in either or both buttocks in double-blind study 
EN3835-302 or EN3835-303 that was at least a 2-level composite improvement on 
CR-PCSS/ PR-PCSS. 
4. Be willing to apply sunscreen to the buttocks before each exposure to the sun. 
5. Be judged to be in good health, based upon the results of a physical examination, and 
laboratory profile at Screening. 
6. Be willing and able to cooperate with the requirements of the study 
7. Be able to read, complete and understand the patient reported outcomes rating 
instruments in English 
11.1.4. 
Inclusion Criteria - Category III Subjects (Post Unblinding of EN3835-302/303) 
In order for Category III subjects to participate in this study, subjects must: 
1. Voluntarily sign and date an informed consent agreement. 
2. Have received active EN3835 in study EN3835-302 or EN3835-303 but did not meet 
eligibility criteria for Category I or Category II status. 
3. Be willing and able to cooperate with the requirements of the study. 
11.1.5. 
Inclusion Criteria - Category I and Category II Subjects Who Opt for 
Retreatment (Post Unblinding of EN3835-302/303) 
Subjects in Category I and Category II who opt for retreatment must meet the following 
additional inclusion criteria to be eligible for retreatment. These subjects must: 
1. Voluntarily sign and date an informed consent agreement for retreatment. 
2. Be willing to apply sunscreen to the buttocks before each exposure to the sun while 
participating in the retreatment portion of the study (ie, Treatment Visit 1 through 
Treatment Visit 4). 
3. Be judged to be in good health, based upon the results of a physical examination, and 
laboratory profile at Screening.  
4. 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 

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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. 
5. Category II subjects must have at least a 1-level composite response reduction compared 
to Day 71 of the EN3835-302/303 study AND no longer maintain a 2-level composite 
response compared to baseline in the EN3835-302/303 study on either or both buttocks 
that is confirmed at a Confirmation Visit. 
11.2. 
Subject Exclusion Criteria 
11.2.1. 
Exclusion Criteria - All Subjects (Through Day 180) 
For the period from completing Day 71 of the double-blind study (EN3835-302 or EN3835-303) 
through Day 180 (Visit 1) of study EN3835-304, in order to be eligible to participate in the 
study, subjects must meet the following exclusion criteria. 
A subject will be excluded from study participation if she: 
1. Intends to or has used any of the following for the treatment of EFP on a buttock at any 
time during the time period from Day 71 of double-blind study EN3835-302 or 
EN3835-303 through Day 180 Visit in study EN3835-304 (approximately 6 months after 
Day 71 of study EN3835-302 or EN3835-303), including (but not limited to): 
a. Liposuction in a buttock  
b. Injections (eg, mesotherapy); radiofrequency device treatments; laser treatment; 
buttock implant treatment; cryolipolysis; or surgery (including subcision and/or 
powered subcision) within a buttock  
c. Any investigational drug or treatment for EFP on a buttock (other than treatment in 
study EN3835-302/303) 
d. Endermologie or similar treatments within a buttock  
e. Massage therapy within a buttock during the 3-month period before observational 
visit 
f. Creams (eg, Celluvera, TriLastin) and/or home therapies to prevent or mitigate EFP 
within a buttock during the 2-week period before observational visit 
2. Intends to use tanning spray or tanning booths during this period. 
3. Any other condition(s) that, in the Investigator’s opinion, might indicate the subject to be 
unsuitable for the study. 
NOTE: After Day 180 Visit assessments are completed in study EN3835-304 and unblinding of 
EN3835-302/303, subjects who received EN3835 in EN3835-302 or EN3835-303 will be placed 
into one of three categories based on their responder status of each of their buttocks at Day 71 in 
study EN3835-302 or EN3835-303 (Section 10.1). Investigators, subjects and all site personnel 
will be blinded to the treatment that the subjects received in the double-blind studies until 
assessments at the Day 180 visit of study EN3835-304 are completed; even if this visit occurs 
after the EN3835-302/303 studies are unblinded by Endo. Investigator, subjects and site 
personnel will be unblinded on Day 180 of study EN3835-304 after Day 180 assessments are 
completed or at an Unscheduled Visit, pending when database lock and unblinding of studies 

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EN3835-302/303 occurs relative to Day 180 of this current study EN3835-304. The following 
additional exclusion criteria will apply after Day 180 to subjects in Categories I, II, and II as well 
as to subjects in Categories I and II who opt to be retreated. 
11.2.2. 
Exclusion Criteria - Category I and Category II Subjects (Post Unblinding of 
EN3835-302/303) 
A Category I or Category II subject will be excluded from study participation if she: 
1. Intends to or has used any of the following for the treatment of EFP on a buttock at any 
time during the course of the study: 
a. Liposuction in a buttock. 
b. Injections (eg, mesotherapy); radiofrequency device treatments; laser treatment; 
buttock implant treatment; cryolipolysis; or surgery (including subcision and/or 
powered subcision) within a buttock. 
c. Any investigational drug or treatment for EFP on a buttock (other than treatment in 
study EN3835-302/303). 
d. Endermologie or similar treatments within a buttock. 
e. Massage therapy within a buttock during the 3-month period before observational 
visit. 
f. Creams (eg, Celluvera, TriLastin) and/or home therapies to prevent or mitigate EFP 
within a buttock during the 2-week period before observational visit. 
2. Has received any collagenase treatments at any time since completion of the double-blind 
study 
3. Any other condition(s) that, in the Investigator’s opinion, might indicate that the subject 
is unsuitable for the study. 
11.2.3. 
Exclusion Criteria - Category III Subjects (Post Unblinding of EN3835-302/303) 
None 
11.2.4. 
Exclusion Criteria Category I and II Subjects Who Opt to Receive Retreatment 
(Post Unblinding of EN3835-302/303) 
A Category I or Category II subject will be excluded from retreatment if she: 
1. Has any of the following systemic conditions: 
a. Coagulation disorder. 
b. Evidence or history of malignancy (other than excised basal-cell or squamous-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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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 
retreatment portion the trial: 
a. Anticoagulant or antiplatelet medication or has received anticoagulant or antiplatelet 
medication (except for ≤150 mg aspirin daily) within 7 days before or 7 days after 
injection of study drug. 
4. Is nursing or providing breast milk during the course of retreatment (Treatment Visit 1 
through Treatment Visit 4). 
5. Is pregnant or intends to become pregnant during the course of retreatment (Treatment 
Visit 1 through Treatment Visit 4). 
6. Intends to use tanning spray or tanning booths in the 30 days prior to and during the 
course of retreatment (Treatment Visit 1 through Treatment Visit 4).  
7. Has a known systemic allergy to collagenase or any other excipient of study drug. 
8. Any other condition(s) that, in the Investigator’s opinion, might indicate the subject to be 
unsuitable for retreatment. 
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 or more of the following 
reasons: 
• An adverse event 
• 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) 
• Treatment with placebo in EN3835-302/303 (determined after unblinding) 
• 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) 

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If a subject discontinues from the study, all end-of-study procedures including safety and 
efficacy assessments should be conducted as detailed in the relevant Schedule of Events 
(Section 5.1 through Section 5.4). 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 for all subjects up through 180 days following studies EN3835-302/303 
is provided in Section 5.1. Beyond Day 180, the Schedule of Events for subjects classified as 
categories I and II and who are eligible and opt to receive retreatment is provided in Section 5.2 
and in observational phase of study Section 5.3. The Schedule of Events for subjects in 
Category II who are not eligible for retreatment, or are in Category I and II and who are eligible 
but opt not to have retreatment, is provided in Section 5.3. The Schedule of Events for Category 
III subjects is shown in Section 5.4. Below are further details where additional instruction about 
the assessments that will be performed is deemed to be needed. 
Unscheduled visits may be done as deemed necessary at any time during the study to ensure 
subject safety; assessments done at unscheduled visits are at the discretion of the investigator. 
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 Screening A/ Day 71 Visit of Double-blind Study (± 14 Days) 
Upon completion of Day 71 assessments in the double-blind study EN3835-302 or EN3835-303, 
a subject will be eligible to enter this open-label extension study. The status of all subjects (eg, 
screen fails) will be kept in the EDC system.  
If the Screening Visit for a subject is greater than 14 days after the subject’s Day 71 of study 
EN3835-302/303, only the unique Screening Visit assessments will be performed (informed 
consent, inclusion and exclusion criteria evaluation, height, weight, and physical examination). 
No subject will be allowed to enroll in the study if the Screening Visit does not occur within 
180 days after Day 71 of Study EN3835-302/303. All changes in medical history occurring 
between completion of study EN3835-302/303 and the Screening Visit of study EN3835-304 
will be considered adverse events and 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). 
12.1.3. 
Medical History 
Since this is a long-term rollover study for subjects that participated and completed the 
double-blind study (EN3835-302 or EN3835-303), in which the subjects’ medical history was 
collected, only newly discovered medical history (events/procedures that occurred prior to 
enrollment in study EN3835-302/303) will be collected (eg, a subject remembers having an 
appendectomy as a child that was not reported in the medical history for EN3835-302/303). 

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12.1.4. 
Study Entry/Observational Assessments (Up to Day 180) 
A subject who gives written informed consent and who satisfies all eligibility criteria 
(Section 11) may be entered into this open-label observational study and complete safety and 
cellulite severity assessments 180 days following their Day 71 Visit in the double-blind study, as 
detailed in Section 5.1. The subject identification number will be carried over from the 
double-blind, placebo-controlled study (EN3835-302/303).  
12.1.5. 
Day 180/Early Termination Visit/Screening B 
Subjects who received active treatment will return at 180 days (±14 days) following their 
Screening Visit (Day 71 of the double-blind studies [EN3835-302 or EN3835-303]) for cellulite 
severity assessments. All assessments will be completed as detailed in Section 5.1 prior to 
unblinding of the subject’s treatment assignment in the double-blind study. Local safety 
assessments (Section 14.6.1) and adverse events will be monitored (Section 14). A subject who 
terminates study participation between Day 71 and Day 180 will have an Early Termination Visit 
that includes the assessments listed for Visit 1 Day 180. 
If unblinding of drug treatment in EN3835-302/303 occurs by the Sponsor prior to a subject’s 
Day 180 visit, Investigators, subjects and site personnel will remain blinded to the subject’s drug 
treatment in the double-blind studies until after the Day 180 assessment have been completed. 
After assessments are completed, unblinding will occur at the site and subjects who received 
placebo will be discontinued, and subjects who received active EN3835 will be classified into 
one of three categories based on responder status of each of their buttocks in the double-blind 
study (Section 10.1). If the subject is categorized to a classification and has ratings that qualify 
for retreatment (ie, all Category I subjects will be offered retreatment; Category II subjects that 
have at least a 1-level composite response reduction compared to Day 71 of the EN3835-302/303 
study AND no longer maintain a 2-level composite response compared to baseline in the 
EN3835-302/303 study on either or both buttocks) the subject may be offered retreatment. If 
there is a composite worsening of cellulite severity of 1-level (ie, worsening of both the 
PR-PCSS and CR-PCSS by at least 1 severity levels) detected in a Category II subject, the 
confirmation of loss of response will be established during a follow-up visit ~2 weeks after the 
loss of response is detected at Day 180 as described in Section 12.2.2.3 (Confirmation Visit). If a 
Category I subject accepts the offer of retreatment at the Day 180 visit, Screening B of the 
Treatment Phase of the protocol may occur on the same day as the Day 180 Visit. If the loss of 
response in a Category II subject is confirmed and the subject accepts the offer of retreatment at 
the Confirmation Visit, Screening B of the Treatment Phase may occur on the same day as the 
Confirmation Visit. If the loss of response is not confirmed, the subject will be considered to not 
have lost response and will not be offered retreatment. 
If the unblinding has not occurred by a subject’s Day 180 visit, an Unscheduled Visit will be 
arranged after unblinding has occurred (see Section 12.4) and the subjects will be classified at 
this Unscheduled Visit or, if received placebo, will be discontinued. If a Category I subject 
decides to accept the offer of retreatment, the subject may be screened (Screening B Visit of the 
Treatment Phase) during the Unscheduled Visit. If a Category II meets eligibility criteria for 
retreatment during the Unscheduled Visit, the loss of response will be confirmed during a 
follow-up visit ~2 weeks after the loss of response is detected as described in Section 12.2.2.3 
(Confirmation Visit). If the loss of response in a Category II subject is confirmed and the subject 

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accepts the offer of retreatment at the Confirmation Visit, Screening B of the Treatment Phase 
may occur on the same day as the Confirmation Visit. If the loss of response is not confirmed, 
the subject will be considered to not have lost response and will not be offered retreatment.  
If a subject does not meet Screening B criteria (eg, positive pregnancy test, elevated liver 
enzymes, etc), the subject maybe rescreened at a later date. 
As stated in Section 10.1, either on Day 180 Visit after assessments have been completed or at an 
Unscheduled Visit, once the study blind is broken, the EN3835-302/303 placebo subjects will be 
discontinued, and subjects who received active EN3835 in their respective double-blind study 
will be classified into one of three categories based on their response in the double-blind study.  
12.2. 
Category I Subjects and Category II Subjects Visits (Post Unblinding 
of EN3835-302/303) 
Assessments to be completed at these visits are detailed in Section 5.2 (Treatment Assessments) 
and in Section 5.3 (Observation Assessments). 
Beginning at Day 180 (ie, approximately 6 months after Day 71 Visit of the double-blind study), 
after Day 180 assessments have been completed in a blinded fashion, all eligible Category I 
subjects will be offered a course of retreatment. Category II subjects who have had at least a 
1-level composite response reduction compared to Day 71 of the EN3835-302/303 study AND 
no longer maintain a 2-level composite response compared to baseline in the EN3835-302/303 
study will be offered a course of retreatment; and assessments to be completed at these 
Treatment Assessments are detailed in Section 5.2. After completing Day 71 of the retreatment 
in this open-label study, the subjects will be assessed at intervals for cellulite severity and safety 
as detailed in Section 5.3 until they have completed approximately 3 years (1080 days) from 
Day 71 of the double-blind study. Category II subjects that have not shown a 1-level composite 
reduction (ie, have maintained a successful response), and/or Category I and/or Category II 
subjects who are eligible for a retreatment course but opt not to receive retreatment will be 
assessed at intervals (Section 5.3) for cellulite severity and safety until they have completed 
approximately 3 years from Day 71 of the double-blind study. If the subject’s buttocks become 
eligible for retreatment based on the ratings of an observational visit and if they have not already 
received a course of retreatment, they will be offered retreatment up to including Observational 
Visit 5 (Month 36). The TRR for composite 1-level responders (ie, Category I) will also be 
assessed at 180 days after the Day 71 Visit of the double-blind study as well as after Treatment 
Visit 4 (Retreatment Day 71) of this open-label study for those buttocks that are retreated. 
Buttocks not retreated will be assessed at each of the observation visits as shown in Section 5.3. 
TRR is defined as a 1-level composite worsening of cellulite severity levels (on both the 
PR-PCSS and CR-PCSS). 
If a treatment period eclipses (or overlaps) a scheduled observational visit, the observational visit 
will be skipped and the subject will re-enter the observational schedule at the next interval visit. 
For example, if a subject initiated retreatment on Day 351 (which would then be Treatment 
Visit 1), the treatment period would proceed for approximately 71 days until Day 421 (Treatment 
Visit 4) and the Observational Visit at Day 360 would be skipped; the subject’s next 
observational visit would be Day 540. 

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Treatments will not be offered to any subject after Visit 5 (Day 1080 ± 30 days; Month 36 ± 
1 month). 
12.2.1. 
Treatment Assessments (Treatment is Optional for Eligible Subjects) 
12.2.1.1. Screening B (Days -14 to -1 Relative to Treatment Visit 1) 
The following procedures will be performed and documented during Screening B: 
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) and review 
training and use materials 
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. Subjects will review subject cellulite assessment training and use materials prior to use of 
the S-GAIS, PR-CIS, Subject Satisfaction with Cellulite Treatment Assessment, and the 
SSRS 
7. Subject Global Aesthetic Improvement Scale (S-GAIS) (Section 13.1.2.2); subjects will 
rate each of their two buttocks while viewing pretreatment images from Day 1 of the 
double-blind study (EN3835-302/303) 
8. 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 
9. Subject will complete the 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  
10. Subject will complete the Subject Self-Rating Scale (SSRS) (Section 13.1.2.5); note this 
assessment is of both left and right buttocks rather than each individual buttock 
11. After the subject has completed the PR-PCSS ratings and after the Investigator has 
reviewed the training and use material for the CR-PCSS, 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 eligibility of the buttocks for retreatment  
12. Record prior and concomitant medications/procedures (Section 12.5) 
13. Physical examination including measurement of body weight and height (Section 14.11) 
14. Vital sign measurements (Section 14.9) 
15. 12-lead ECG (Section 14.10) 

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16. Collection of samples for: 
a. Clinical laboratory testing (Section 14.7) 
b. Anti-AUX-I and anti-AUX-II antibody testing (Section 14.8) 
c. Serum pregnancy testing (Section 14.7) 
17. Injection site reactions/local tolerability in the buttocks (Section 14.6.1) 
18. Adverse events (Section 14) 
12.2.1.2. Selecting and Marking Dimples During Treatment Visits 
Selection of dimples to be treated in the eligible 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). Category I subjects and Category II subjects eligible for retreatment can receive up 
to 3 retreatment visits of study drug as outlined in Section 5.2 unless the buttock is dimple-free 
(score of 0 on CR-PCSS as reported by the Investigator) at Treatment Visit 1, Treatment Visit 2 
and/or Treatment Visit 3. During each retreatment visit, the buttocks to be treated 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 the 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 retreatment; retreatment 
consists of 12 injections per buttock (up to 24 injections total in two buttocks) per retreatment 
visit. Because the goal of retreatment 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 retreated at the designated treatment visits but 
injections must all be within the buttocks (12 injections per buttock) for all 3 visits. Each eligible 
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 
retreatment in the contralateral buttock (if eligible) at Treatment Visit 2 if the buttock was 
retreated at Treatment Visit 1, and when they return for Treatment Visit 3, 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 retreatment, 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. 

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Each of the buttocks to be retreated 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 
 
12.2.1.3. Digital Photography during Treatment Visits 1, 2, and 3 
During each retreatment visit, each of the 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.  
12.2.1.4. Treatment Visit 1 
12.2.1.4.1. Treatment Visit 1: Pre-Injection 
For each subject, the Sponsor will inform the site of the areas eligible for retreatment based on 
the PR-PCSS/CR-PCSS ratings obtained during Treatment Visit 1. Each buttock will be 
photographed during the retreatment visits. Prior to injection, the following procedures will be 
conducted: 
1. Take digital photography of each buttock before marking dimples and injection sites on 
the buttocks being retreated (Section 13.1.1). Note: both buttocks will be photographed, 
regardless of treatment. 
2. Subjects will get instruction on the use of the PR-PCSS (Patient Instructions for Use of 
PR-PCSS) and review training and use materials. 

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3. Subjects will rate each of their buttocks using the PR-PCSS (Section 13.1.2.1); the 
Investigator is blinded to these scores. 
4. The Investigator will review training and materials for the use of the CR-PCSS. 
5. The Investigator will conduct live assessments of subject’s cellulite severity of each of 
the buttocks using the CR-PCSS (Section 13.1.2.6); the subject is blinded to these ratings. 
6. Record concomitant medications/procedures (Section 12.5). 
7. Vital sign measurements (Section 14.9). 
8. Collection of samples for: 
a. Urine pregnancy testing (Section 14.7). 
9. Select and mark dimples to be treated in each of the buttocks (Section 12.2.1.2). 
10. Take digital photograph of each of the buttocks after marking dimples and injection sites 
(Section 13.1.1).  
11. For eligible buttock(s), obtain kit number(s) of study treatment. 
12.2.1.4.2. 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 
buttocks being retreated. 
3. Vital sign measurements (Section 14.9). 
4. Injection site reactions and local tolerability (Section 14.6.1). 
5. Adverse events (Section 14). 
12.2.1.5. Treatment Visits 2 and 3 (Day 22 ± 3 days and Day 43 ± 3 days)  
12.2.1.5.1. Treatment Visits 2 and 3: Pre-injection 
1. Record concomitant medications/procedures (Section 12.5). 
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 the buttock(s) receiving retreatment before marking dimples and 
injection sites (Section 13.1.1). Note: both buttocks will be photographed, regardless of 
treatment. 

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6. Subject Cellulite Assessments, after review of training and use materials, 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). 
7. Investigator Cellulite Assessments conducted, after review of training and use material, 
of each of the buttocks receiving retreatment 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). 
8. Select and mark dimples to be treated in each buttock receiving retreatment 
(Section 12.2.1.2). 
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. 
12.2.1.5.2. 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 
being retreated. 
3. Vital sign measurements (Section 14.9). 
4. Injection site reactions and local tolerability (Section 14.6.1). 
5. Adverse events (Section 14). 
12.2.1.6. Treatment Visit 4 (Day 71 + 5 days) 
The following procedures will be performed at Visit 4: 
1. Record concomitant medications/procedures (Section 12.5). 
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. Urine pregnancy test (Section 14.7). 
c. Anti-AUX-I and anti-AUX-II antibody testing (Section 14.8). 
5. Digital photographs of the buttock(s) receiving retreatment (Section 13.1.1). 
6. Subject will review training and use materials for the PR-PCSS, S-GAIS, PR-CIS, 
Subject Satisfaction with Cellulite Treatment Assessment, and SSRS. 

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7. Subject Cellulite Assessment of each retreated buttock using the photographic image 
(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); subjects 
will rate each of their two buttocks while viewing pretreatment images from Day 1 of 
the double-blind study (EN3835-302/303). 
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 
while viewing images from Treatment Visit 4 (Day 71) of EN3835-304. 
d. Subject will complete the 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 and is conducted while viewing images from Treatment 
Visit 4. 
e. Subject will complete the Subject Self-Rating Scale (SSRS) (Section 13.1.2.5); note 
this assessment is of both left and right buttocks rather than each individual buttock. 
8. Investigator Cellulite Assessments will be conducted, after the review of training and use 
material for the CR-PCSS, of each of the buttock(s) receiving retreatment using: 
a. Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) live assessment 
of subject (Section 13.1.2.6). 
9. Injection site reactions and local tolerability (Section 14.6.1). 
10. Adverse events (Section 14). 
After Treatment Visit 4, retreated subjects enter/re-enter the observational phase of the study 
with assessments of safety and TRR. If an observational visit was scheduled to occur during a 
Treatment Phase visit (Screening B through Treatment Visit 4), the observational visit would be 
skipped and the subject would enter/re-enter the Observation Phase visits at the next interval 
visit.  
12.2.2. 
Observation Assessments 
12.2.2.1. Observation Visit 2 (Day 360 Relative to Day 71 of the Double-blind Study) 
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 each of the buttocks (Section 13.1.1). 
4. Subjects will get instruction on the use of the PR-PCSS (Section 13.1.2.1) and review 
training and use materials for the PR-PCSS, the PR-CIS, the SSRS and the Subject 
Satisfaction with Cellulite Treatment assessments. 
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. 

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6. Subject Global Aesthetic Improvement Scale (S-GAIS) (Section 13.1.2.2); subjects will 
rate each of their two buttocks while viewing pretreatment image from Day 1 of the 
double-blind study (EN3835-302/303). 
7. 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. 
8. Subject will complete the 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.  
9. Subject will complete the Subject Self-Rating Scale (SSRS) (Section 13.1.2.5); note this 
assessment is of both left and right buttocks rather than each individual buttock. 
10. After the subject has completed the PR-PCSS ratings and after the Investigator reviews 
the training and use materials for the CR-PCSS, 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 to remain blinded to these ratings. 
11. Record prior and concomitant medications/procedures (Section 12.5). 
12. Collection of samples for: 
a. Anti-AUX-I and anti-AUX-II antibody testing (Section 14.8). 
13. Local safety assessments (Section 14.6.1). 
14. Adverse events (Section 14). 
12.2.2.2. Observation Visits 3-5/EOS/Early Termination (Day 540 – Day 1080/EOS/Early 
Termination) 
1. Record concomitant medications/procedures (Section 12.5). 
2. Collection of samples for: 
a. Anti-AUX-I and anti-AUX-II antibody testing (Section 14.8). 
3. Digital photographs of each of the buttocks (Section 13.1.1). 
4. Subjects will get instruction on the use of the PR-PCSS (Section 13.1.2.1) and review 
training and use materials for the PR-PCSS, S-GAIS, PR-CIS, SSRS, and the Subject 
Satisfaction with Cellulite Treatment assessments. 
5. Subject Cellulite Assessment of each of the two buttocks using the photographic image 
(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); subjects 
will rate each of their two buttocks while viewing pretreatment image from Day 1 of 
the double-blind study (EN3835-302/303). 
6. 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. 

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7. Subject will complete the 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. 
8. Subject will complete the Subject Self-Rating Scale (SSRS) (Section 13.1.2.5); note this 
assessment is of both left and right buttocks rather than each individual buttock. 
9. Investigator Cellulite Assessments will be conducted, after the Investigator reviews 
training and use materials for the CR-PCSS, of each of the buttocks live using: 
10. Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) live assessment of 
subject (Section 13.1.2.6). 
11. Check ePRO for a potential requirement for a confirmation visit. 
12. Local safety assessments (Section 14.6.1). 
13. Adverse events (Section 14). 
12.2.2.3. Confirmation Visits 
Time to reduction of a ≥1 level and/or ≥2-level composite improvement in cellulite severity 
compared to the level at Day 71 of the double-blind study will be assessed by both the PR-PCSS 
and the CR-PCSS. If, during the study, there is a composite worsening of cellulite severity of 
1-level (ie, worsening of both the PR-PCSS and CR-PCSS by 1 severity levels), the confirmation 
of loss of response will be established during a follow-up visit ~2 weeks after the loss of 
response is first detected. The following procedures will be completed at the Confirmation 
Visits: 
1. Digital photographs of each of the buttocks. 
2. Subject Cellulite Assessment of each of the two buttocks, after reviewing the training and 
use materials, using the photographic image (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). 
3. Investigator Cellulite Assessments of each of the buttocks, after reviewing the training 
and use material, using: 
a. Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) live assessment 
of subject (Section 13.1.2.6). 
NOTE: Subjects showing a confirmed composite worsening of cellulite severity of 1-level will 
be offered retreatment and will continue with annual safety and immunogenicity assessments for 
up to 3 years after Day 71. Subjects who do NOT show a confirmed composite worsening of 
cellulite will be considered to not have a worsening, will not be offered retreatment, and will 
continue with annual safety and immunogenicity assessment for up to 3 years after Day 71. 

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12.3. 
Category III Subjects Visits (Post Unblinding of EN3835-302/303) 
Assessments to be completed at these visits are detailed in Section 5.4. Category III subjects are 
to return every 6 months during the first two years and then annually until they have completed 
1080 days (3 years) following Day 71 of the double-blind study for safety evaluations. Category 
III subjects receive no additional treatments during the study. 
12.3.1. 
Observation Visits 2-5/EOS/Early Termination (Day 360 – Day 1080/EOS/Early 
Termination) 
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. Record concomitant medications/procedures (Section 12.5). 
4. Collection of samples for: 
a. Anti-AUX-I and anti-AUX-II antibody testing (Section 14.8).  
5. Local safety assessments (Section 14.6.1). 
6. Adverse events (Section 14). 
12.4. 
Unscheduled Visit 
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, however no photographs or cellulite severity assessments will be done at 
unscheduled visits. 
If unblinding of Investigator, subject and site personnel to the treatment that the subject received 
in the double-blind study EN3835-302/303 does not occur on Day 180 Visit after all assessments 
are completed, then an unscheduled visit may be arranged to unblind the subject to the treatment 
received. Following unblinding of EN3835-302/303, subjects who received placebo will be 
discontinued, and subjects who received active EN3835 will be classified into one of three 
categories based on responder status (Section 10.1) and proceed as described in Section 12.1. 
12.5. 
Prior and Concomitant Medications and Procedures 
All prior medications will be recorded; the word ‘prior’ refers to the period from the last visit 
from the previous Phase 3 clinical study through the signing of informed consent in the EN3835-
304 study. 
All concomitant medications (including over-the-counter medications) including those to treat 
EFP, taken by the subject during the course of the EN3835-304 study (ie, after informed consent 
for EN3835-304 is signed) will be recorded.  
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. 

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12.5.1. 
Prohibited Medications or Procedures 
For eligible Category I and Category II subjects who opt for retreatment, the following 
medications are prohibited during the retreatment phase of the study (Table 4): 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 this time. 
Table 4: 
Concomitant Medication Restrictions for Category I and Category II 
Subjects During the Retreatment Phase of Study (Treatment Visits 1 - 4) 
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. 
12.6. 
Treatment Compliance 
Eligible Category I and/or Category II subjects may 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).  
For Category III subjects and Category I and Category II subjects that opt not to receive 
treatment, this study is observational in nature, and no additional treatments are to be 
administered.  

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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 to assess certain cellulite severity 
parameters at specific intervals (see Section 5.1 through Section 5.3, Schedule of Events). After 
Day 180 Visit and unblinding of the double-blind studies EN3835-302/303, photography will be 
limited to Category I and Category II subjects. At each designated visit requiring photography, 
the Investigator or qualified designee will photograph each region 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 targeted 
region while the subject is standing in a consistent, standardized relaxed standing pose, 
ie, standing position with relaxed gluteus muscles. 
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 assessments 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 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.  
At Screening (eg, Day 71/EOS of the double-blind study) and at the beginning of each visit 
where photography is to be captured, subjects will have digital photographs taken of each of their 
buttock(s). Subjects will be given instructions in the proper use (Patient Instructions for Use of 
PR-PCSS) of the PR-PCSS, will review training and use material, and then perform the 
PR-PCSS for each of the targeted areas (Appendix B). While viewing the digital images of each 
of their buttocks on a standardized computer monitor and using the PR-PCSS for buttock, 
subjects will be instructed to answer the following question for each buttock: Today, how would 

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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) 
At each of the visits designated to capture the S-GAIS in Section 5.1 through Section 5.3, 
subjects will review training and use materials for S-GAIS, and complete the S-GAIS for each of 
the buttocks as described below using the pretreatment Day 1 digital image (Baseline) from the 
double-blind studies (EN3835-302/303) 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 pretreatment Day 1 digital images from the double-blind study (EN3835-302/303) 
alongside their current 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 ePRO 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. 
−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. 

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13.1.2.3. Patient Reported Cellulite Impact Scale (PR-CIS) 
At each of the visits designated to capture the PR-CIS in Section 5.1 through Section 5.3; 
subjects will review training and use materials, and 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 from 0 (not at all) to 10 (extremely). 
A PR-CIS total score and an abbreviated PR-CIS score (excluding question 5) will be derived 
from these 6 individual questions. 
This variable will be entered directly into the ePRO 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 designated visits, subjects will review training materials and will be instructed to answer a 
question related to their treated buttocks while viewing digital images of their buttocks. The 
subject will view each of their pretreatment Day 1 digital images from the double-blind study 
(EN3835-302/303) alongside their current study visit digital images of their buttocks to aid in the 
assessment. 
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 ePRO 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. 
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 subject will review training and use materials for the 
SSRS. The subject will be asked to respond to the question related to the satisfaction with 
appearance of the cellulite on their buttocks. No photographs or reference to previous ratings or 

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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). 
To complete the SSRS, 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 ePRO 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. Investigators will review training and use materials at each visit prior to the use of the 
CR-PCSS.  
At the Day 71 visit during the double-blind study (which also serves as the Screening visit for 
the current study), the Investigator will determine severity of cellulite of each of the two buttocks 
via live assessment of the subject using the CR-PCSS for the buttock (Appendix C) after the 
subject has completed her self-assessment using the PR-PCSS for the buttock (Appendix B). 
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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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. All AEs that are reported between the completion of studies 
EN3835-302/303 and the Day 180 Visit will be recorded and evaluated as appropriate. 
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 and/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) 

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• 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) 
• 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 

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the AE continued into an active treatment phase, the relationship would be assessed for the active 
treatment phase only if the AE worsened. 
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. 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 (whether the site was injected in the 
double-blind study (EN3835/302/303) or in this open-label study (EN3835-304)), including 
acute (eg, erythema, bruising, pain, nodules/mass, ulceration, blistering, pruritus, swelling, 
and/or induration) and/or chronic (eg, skin thickening, fibrosclerosis, peau d’orange changes) 
cutaneous adverse events, will be recorded and evaluated for seriousness and severity (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 12.6) 
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. 

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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. 
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 study treatment (if applicable) and 
will not be eligible for retreatment while pregnant, but may remain in the study for observational 
purposes and may be considered for retreatment, if eligible, when no longer pregnant or 
breastfeeding. 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. 

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14.7. 
Clinical Laboratory Determinations 
Clinical laboratory tests will be conducted according to the Schedule of Events (Section 5.1 and 
Section 5.2). 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.  
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. 

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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 the Day 71 
visit from the double-blind study (EN3835-302 or EN3835-303), the results of which will be 
data transferred to the Screening Visit of this open-label study if the Screening Visit occurs 
within 14 days of the Day 71 visit of the double-blind study. Additionally, a serum pregnancy 
test will be performed at the Screening B visit of any Category I and/or eligible Category II 
subject screening for the Treatment phase of the study. Urine pregnancy tests will be performed 
at the other study visits (refer to Section 5.1 and Section 5.2). 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. 
14.8. 
Anti-AUX-I and Anti-AUX-II Antibodies 
Serum samples will be collected and will be tested for binding anti-AUX-I and anti-AUX-II 
antibody testing at the visits designated in Section 5.1 through Section 5.4. For Category I 
subjects and/or eligible Category II subjects receiving retreatment, a subset (based on every other 
sample from the Treatment Visit 4 upper and lower quadrants of binding antibody titers) of 
subject samples will be tested for neutralizing antibodies from these visits; additional samples 
will be retained. 
The serum samples obtained will be processed, stored and then shipped on dry ice to the 
designated central clinical laboratory before forwarding to Endo’s appointed laboratory for the 
determination of anti-AUX-I and anti-AUX-II antibodies according to the laboratory manual. 

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14.9. 
Vital Signs 
Vital sign measurements will be documented as described in each of the Schedule of Events 
(Section 5.1 and Section 5.2). These parameters include pulse rate, respiratory rate, systolic and 
diastolic blood pressure, and body temperature. Pulse and blood pressure readings will be taken 
after the subject has been sitting for 5 minutes. 
The Investigator will review all vital sign values for clinical significance prior to discharge. Any 
vital sign value 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). 
For eligible Category I and Category II subjects receiving retreatment, vital signs will be 
assessed at the time points shown in Table 9 after the subject has rested for at least 5 minutes. 
Table 9: 
Vital Signs Measurements on Injection Day 
Time Point Relative to Last Injection 
Blood Pressure, Respiratory 
Rate, and Pulse Rate 
Body Temperature 
Up to 4 hours (before treatment) 
X 
X 
Approximately 15 minutes after 
X 
 
Approximately 30 minutes after 
X 
X 
14.10. 
Electrocardiogram 
Performing a 12-lead electrocardiogram (ECG) is not necessary if Screening B visit date is 
within 12 months of obtaining an ECG during the double-blind study (EN3835-302/303). 
If the date of Screening B visit is later than 12 months since obtaining the ECG in study 
EN3835-302/303, subjects will have a resting 12-lead ECG performed during the Screening B 
visit. 
A qualified physician will interpret, sign, and date the ECGs. Electrocardiogram assessments 
must be “within normal limits” or interpreted as “abnormal, not clinically significant” for the 
subject to be included in the study. 
Any ECG result 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). 
14.11. 
Physical Examination 
A complete physical examination will be performed at the double-blind Day 71/Screening Visit 
and at additional Visits as designated in Section 5.1 and Section 5.2. All examinations will be 
performed by a physician or health care professional listed on the Form FDA 1572 and licensed 
to perform physical examinations. Height and body weight will be measured and recorded at 
screening and at designated visits where physical exams are to be conducted. Height and body 
weight will be measured at additional visits for Category I and retreatment-eligible Category II 
subjects (in the absence of a full physical exam) as designated in Section 5.2. 

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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). 
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. 
STATISTICAL CONSIDERATIONS AND METHODS 
17.1. 
Determination of Sample Size 
Approximately 420 active subjects who completed the EN3835-302/303studies will rollover to 
this study. This sample size should be adequate to determine long-term safety and TRR to 
EN3835. 
17.2. 
Subject Populations 
For subjects entering the open-label study period, subjects who received active EN3835 in their 
double-blind study (EN3835-302/303) will be classified into one of three categories: 
Category I: 
1-Level Composite Responders 
Category II: 
2-Level Composite Responders 
Category III: Non-Composite Responders 
Based on subject category, three (3) populations are considered in the statistical analysis of the 
study: overall safety population, Day 180 Observational Population, and Time to Reduction in 
Response (TRR) Population. 
17.2.1. 
Overall Safety Population 
The overall safety population is defined as all subjects who enter the open-label study period and 
received EN3835 in EN3835-302 or EN3835-303. This population will include all Category I, II, 
and III subjects. All safety analyses will be based on this population. In addition, the safety data 
will be summarized separately prior to retreatment and after the retreatment period.  
17.2.2. 
Day 180 Observational Population  
The Day-180 observational population will include all rollover subjects from studies 
EN3835-302/303. The safety analysis for the data obtained from Screening to Day 180 will be 
based on this population. 
17.2.3. 
Time to Reduction of Response (TRR) Population 
The TRR population is defined as all subjects who have at least a 1-level or 2-level improvement 
in both CR-PCSS and PR-PCSS ratings during the double-blind study or open label study (for 
retreated subjects) for either/both treated buttocks. This population will include Category I and II 
subjects. TRR will be evaluated separately for subjects who had a 1-level and 2-level composite 
improvement in CR-PCSS and PR-PCSS during studies in each buttock. The efficacy data will 
be summarized separately for ‘prior to retreatment’ and ‘after the retreatment period.’ 
17.3. 
Subject Disposition 
The number of subjects included in each study population will be summarized. The number and 
percentage of subjects completed and discontinued will be presented. Reasons for 
discontinuation as recorded on the eCRF will be summarized (number and percentage) for all 
subjects. 

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17.4. 
Demographics and Other Baseline Characteristics 
Demographic and baseline characteristics, including age, race, and baseline values will be 
summarized for each study population. The descriptive statistics will include the number and 
percentage for categorical response variables and number, mean, standard deviation, minimum, 
and maximum for continuous variables. 
17.5. 
Efficacy Analyses 
Cellulite (efficacy) assessments include: 
• PR-PCSS: patient reported 5-point scale ranging from 0 (no cellulite) to 4 (severe 
cellulite). 
• CR-PCSS: clinician reported 5-point scale ranging from 0 (no cellulite) to 4 (severe 
cellulite). 
• PR-CIS: patient reported cellulite impact scale to assess 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 from 0 (not at all) to 10 (extremely). A PR-CIS total score and an abbreviated 
PR-CIS score (excluding question 5) will be derived from these 6 individual 
questions. 
• Subject Global Aesthetic Improvement Scale (S-GAIS): a 7-level scale ranging from 
3 (very much improved) to −3 (very much worse).  
• Subject Satisfaction With Cellulite Treatment Assessment: a 5-point scale ranging 
from +2 (very much satisfied) to −2 (very much dissatisfied). 
• Subject Self-Rating Scale (SSRS): a 7-level scale that ranges from 0 (extremely 
dissatisfied to 6 (extremely satisfied). 
All cellulite assessments will be performed on each individual treatment area. Treatment areas 
will be evaluated separately. 
Efficacy analyses may be performed at any time point determined to be necessary by the 
Sponsor. 
17.5.1. 
Analyses 
The analyses of cellulite assessments will be based on the TRR population(s). The TRR will be 
defined from time of assessing the efficacy (ie, Day 71 at EN3835-302/303, or Day 71 in the 
retreatment period) to the study visit at which a composite 1-level reduction of response in both 
PR-PCSS and CR-PCSS is observed.  
The defined endpoints will include: 
• Proportion of subjects with reduction of response: 
− Proportion of subjects with both CR-PCSS and PR-PCSS ratings worsening 
1-level compared to their corresponding score at Day 71 in the studies.  

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− Proportion of subjects with both CR-PCSS and PR-PCSS ratings back to their 
baseline (Day 1 of the double-blind study) or worse. 
− Proportion of subjects with both CR-PCSS and PR-PCSS ratings worsening 
2-levels compared to their corresponding score at Day 71 in the studies. 
− Proportion of subjects with either CR-PCSS or PR-PCSS ratings worsening 
2-levels compared to their corresponding score at Day 71 in the studies. 
• Proportion of subjects at each level of improvement in the PR-PCSS. 
• Proportion of subjects at each level of improvement in the CR-PCSS. 
• Changes in the PR-CIS total scores from baseline. 
• Proportion of subjects at each level of improvement in the S-GAIS. 
• Proportion of subjects at each level of improvement in Subject Satisfaction with 
Cellulite Treatment. 
• Proportion of subjects at each level of improvement in the SSRS. 
All results for each endpoint based on the collection time points as described in Section 5.1 
through Section 5.3 will be derived and summarized by treated area, subject category, and study 
visit (day) using appropriate descriptive statistics. The baseline or reference data point will be 
detailed in the Statistical Analysis Plan (SAP). 
17.6. 
Safety Analyses 
The following variables are safety endpoints. 
• AEs: Mapped to preferred term using the Medical Dictionary for Regulatory 
Activities (MedDRA) 
• Injection site reactions/local tolerability in treatment area (through subject and 
Investigator reporting) 
• Vital signs 
• Laboratory testing 
AEs will be summarized by treatment exposure category, ie, initial exposure to EN3835 in 
EN3835-302/303 versus re-exposure to EN3835 in this open-label study (EN3835-304) using 
descriptive statistics.  
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. The version used in this study will be stated in the 
Data Management Plan. Prior medication will be defined as any medication with a start date 
prior to the study start reference date. Concomitant medication is defined as any medication with 
a start date on or after the study start reference date or reported as ongoing. Any medications 
started after the last dose of study drug will be considered as follow-up medications. 

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Prior and concomitant medication use will be summarized descriptively by the number and 
percentage of subjects receiving each medication within each therapeutic class. Multiple use of 
the same medication by a subject will be counted only once. 
17.6.2. 
Study Drug Exposure 
For those subjects that elect, are eligible, and do receive retreatment, the number of injections per 
treatment area (buttock) and in total will be summarized by counts and percentages. The number 
of dimples per treatment area (buttock) treated will be summarized with counts and percentages.  
17.6.3. 
Adverse Events 
The MedDRA dictionary will be used to code AEs. The version used in this study will be stated 
in the Data Management Plan. 
Descriptive statistics (the number and percentage) for subjects reporting TEAEs 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. 
SAEs and AEs leading to premature discontinuation of study drug will be summarized. Listings 
will be presented for subjects with SAEs, subjects with AEs leading to discontinuation, and 
subjects who die (if any).  
17.6.4. 
Vital Signs 
Descriptive statistics for vital signs (eg, systolic and diastolic blood pressure, pulse rate, 
respiratory rate, temperature, and body weight) and their changes from baseline at each visit and 
at the end of treatment visit will be presented.  
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 SAP. A listing of all AEs for subjects with PCI vital signs will also be provided. 
17.6.5. 
Clinical Laboratory Parameters 
Descriptive statistics for clinical laboratory values in International System of Units (SI units) and 
changes from baseline will be presented for each clinical laboratory parameter. 
The number and percentage of subjects with PCI post-baseline clinical laboratory values will be 
tabulated. The criteria for PCI laboratory values will be detailed in the SAP. A listing of all 
subjects with PCI laboratory values will also be provided. 
17.7. 
Immunogenicity Analyses 
Immunogenicity variables include anti-AUX-I/anti-AUX-II binding antibody results. Binding 
antibody levels will be determined from samples collected on scheduled visits (see Section 5.1 
through Section 5.4). 

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Descriptive statistics (percent of positive measurements and average antibody level) will be 
presented for anti-AUX-I and anti-AUX-II antibody levels at each time point by treated area and 
by treatment exposure category. Average antibody levels will be summarized on logarithmically 
transposed titer values. 
In addition, a subset of subjects’ samples with anti-AUX-I and anti-AUX-II neutralizing 
antibodies will be summarized using appropriate descriptive statistics. 
17.8. 
Pharmacokinetic Analyses 
Not applicable. 
17.9. 
Pharmacodynamic Analyses 
Not applicable. 
17.10. 
Other Data (eg, Health Economics/QOL, Pharmacogenetic, etc) 
Not applicable. 
17.11. 
Interim Analysis 
No interim analysis is planned for this study. 
17.12. 
Statistical Software 
Statistical analyses will be performed using Version 9.3 (or higher) of SAS® (SAS Institute, 
Cary, NC). 
 

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18. 
STUDY DRUG MATERIALS AND MANAGEMENT 
18.1. 
Study Drug Identity 
EN3835 is manufactured and supplied by Endo. 
EN3835 is a sterile lyophilized powder consisting of 0.92 mg of collagenase clostridium 
histolyticum, 18.9 mg sucrose, 1.1 mg Tris, 37.7 mg mannitol, and hydrochloric acid qs to 
pH 8.5. 
EN3835 sterile diluent for reconstitution is 0.6% sodium chloride and 0.03% calcium chloride in 
water for injection. 
18.2. 
Study Drug Packaging and Labeling 
Each vial of study drug and diluent will minimally be labeled with contents, Sponsor 
identification, storage, administration/use, and appropriate cautions statements; additionally, 
study drug will be labeled with kit number. Each kit will contain one vial each of EN3835 and 
sterile diluent. 
18.3. 
Study Drug Storage 
All study drug will be provided by Endo. Study drug must be stored in an appropriate, secure 
area. Study drug must be kept in a temperature-monitored refrigerator (2°C-8°C) with locked 
access until used or returned to Endo. 
18.4. 
Study Drug Preparation 
Refer to the Reconstitution Instructions for detailed preparation instructions. 
For each dose session, the interactive web response system (IWRS) will dispense 1 kit. Eight 
0.9-mL syringes will be prepared from each vial of EN3835, 8 syringes/kit (in the case of 2 
qualifying buttocks). If only 1 qualifying buttock, only four 0.9-mL syringes will be prepared 
from each vial of EN3835, with the remainder of the reconstituted unused study drug solution 
stored in a secure location until reconciled and returned by the Clinical Research Associate. 
Used drug vials should be returned to the kit carton and stored in a secure location until 
reconciled and returned by the Clinical Research Associate (CRA). Dispose of used needles and 
syringes per local regulations. 
The reconstituted study drug solution should be administered as soon as possible after 
reconstitution. The study drug solution can be kept at room temperature for up to 4 hours 
following the start of the reconstitution process. If more time is needed prior to injection, 
refrigerate the reconstituted drug vial for up to 24 hours. Remove reconstituted drug vial from 
the refrigerator and allow it to stand at room temperature for 15 minutes prior to preparing the 
administration syringes and injection of study drug. 

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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 drug and unused kits 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 
• PR-CIS 
• Subject Satisfaction with Cellulite Treatment 
• SRSS 
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. 
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. 
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 

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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. 
The unique subject identification number will be carried over from the double-blind, 
placebo-controlled study (EN3835-302/303). 

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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. 
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 

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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. 
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 has 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 

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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. 
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 
iii. A clear statement of approval of the protocol and the informed consent text with 
version date, and authorization for the study to proceed 

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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