A Phase 2 Open-Label Study of EN3835 In The Treatment of Edematous Fibrosclerotic Panniculopathy
Phase: PHASE2
Conditions: Edematous Fibrosclerotic Panniculopathy, Cellulite
Sponsor: Endo Pharmaceuticals



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2. 
SUMMARY OF CHANGES 
Not applicable. 

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4. 
SYNOPSIS 
Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
Title of Study: A Phase 2 Open-label Study of EN3835 in the Treatment of Edematous Fibrosclerotic 
Panniculopathy 
Lead Principal Investigator: TBD 
Study Period:  
Estimated date first subject enrolled: Nov-2017 
Estimated date last subject completed: Jul-2018 
Phase of Development: 2 
Objectives: 
Primary Objective: 
 
To assess the safety of EN3835 in the treatment of edematous fibrosclerotic panniculopathy 
(EFP), commonly known as cellulite, in adult women 
Secondary Objective: 
 
To assess effectiveness of EN3835 in the treatment of EFP 
Study Design: This study is a Phase 2, open-label study of safety and effectiveness of EN3835 in the 
treatment of EFP in adult women. Subjects will be screened for study eligibility within 14 days prior to 
enrolling in this study. Subjects with at least 2 bilateral treatment areas (bilateral buttocks or bilateral 
posterolateral thighs) (also referred to as a region) (eg, their left and right buttocks or left and right 
posterolateral thighs) with mild, moderate or severe levels of cellulite as assessed by the Investigator 
using the Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) and a Hexsel Cellulite 
Severity Scale no greater than 13 will be eligible. If both their left and right buttocks AND left and right 
posterolateral thighs are eligible, one pair will be randomly selected as the assigned treatment areas. 
Subjects will receive an open-label treatment course which consists of up to 3 treatment visits  
(ie, Day1, Day 22, and Day 43). Each treatment visit will consist of 12 injections (0.3 mL per injection 
of EN3835 0.07 mg/injection) in each of the treatment areas of the region for a total volume of 7.2 mL 
(1.68 mg). Selection of dimples to be treated in the assigned treatment areas will be at the discretion of 
the Investigator. End-of-study will occur at study Day 180. 
At each treatment visit, the Investigator will first conduct a live assessment of each treatment area of the 
assigned region using the CR-PCSS. The Investigator will then select and mark the dimples to be treated 
within each treatment area. All the assessments must be done before marking the dimples for injection. 
At Day 180 (End of Study/Early Termination), The Investigator will conduct live assessments of each of 
the treatment area using the CR-PCSS. The subject will complete the Subject Satisfaction with Cellulite 
Treatment assessment. 
In a photographic sub-study at two sites, subjects will return to the site to have their treated areas 
photographed at 1, 3, 6, and 13 days after each treatment visit to assess local site reactions 
post-injection. 
Number of Subjects (planned): Up to 150 
Study Center(s): Approximately 10 sites in United States 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
Diagnosis and Inclusion/Exclusion Criteria: 
Inclusion Criteria: 
1. Voluntarily sign and date an informed consent agreement 
2. Be a female ≥18 years of age 
3. At Screening visit, have at least one treatment region (bilateral buttocks or bilateral 
posterolateral thighs), with each region treatment area having: 
a. a score of 2 (mild) or greater as reported by the Investigator (CR-PCSS), and  
b. a Hexsel CSS score no greater than 13 
4. Be willing to apply sunscreen to the assigned treatment areas before each exposure to the sun 
while participating in the study (ie, Screening through end of study) 
5. Be judged to be in good health, based upon the results of a medical history, physical 
examination, and laboratory profile at Screening 
6. 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 
7. Be willing and able to cooperate with the requirements of the study 
8. Be able to read, complete and understand the patient-reported outcomes rating instruments in 
English 
Exclusion Criteria:  
A subject will be excluded from study participation if she: 
1. Has any of the following systemic conditions: 
a. Coagulation disorder 
b. Evidence or history of malignancy (other than excised basal-cell carcinoma) unless there 
has been no recurrence in at least 5 years 
c. History of keloidal scarring or abnormal wound healing 
d. Concurrent diseases or conditions that might interfere with the conduct of the study, 
confound the interpretation of the study results, or endanger the subject’s well-being. Any 
questions about concurrent diseases should be discussed with the Medical Monitor. 
e. Evidence of clinically significant abnormalities on physical examination, vital signs, 
electrocardiogram (ECG), or clinical laboratory values 
2. Has any of the following local conditions in the area to be treated: 
a. History of lower extremity thrombosis or post-thrombosis syndrome 
b. Vascular disorder (eg, varicose veins, telangiectasia) in area to be treated 
c. Inflammation or active infection 
d. Active cutaneous alteration including rash, eczema, psoriasis, or skin cancer 
e. Has a tattoo and/or a mole located within 2 cm of the site of injection 
3. Requires the following concomitant medications before or during participation in the trial: 
a. Anticoagulant or antiplatelet medication or has received anticoagulant or antiplatelet 
medication (except for ≤150 mg aspirin daily) within 7 days before injection of study drug 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
4. Has used any of the following for the treatment of EFP on the legs or buttocks 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 the areas of the body selected for treatment during the 12-month period 
before injection of study drug 
b. Injections (eg, mesotherapy); radiofrequency device treatments; laser treatment; buttock 
and/or thigh implant treatment, cryolipolysis, or surgery (including subcision and/or 
powered subcision) within the assigned treatment areas during the 12-month period before 
injection of study drug 
c. Endermologie or similar treatments within the assigned treatment areas during the 6-month 
period before injection of study drug 
d. Massage therapy within the assigned treatment areas during the 3-month period before 
injection of study drug 
e. Creams (eg, Celluvera™, TriLastin®) to prevent or mitigate EFP within the assigned 
treatment areas during the 2-week period before injection of study drug 
5. Is presently nursing or providing breast milk 
6. Intends to become pregnant during the study 
7. Intends to initiate an intensive sport or exercise program during the study 
8. Intends to initiate a weight reduction program during the study 
9. Intends to use tanning spray or tanning booths during the study 
10. Has received an investigational drug or treatment within 30 days before injection of study drug 
11. Has a known systemic allergy to collagenase or any other excipient of study drug 
12. Has received any collagenase treatments at any time prior to treatment 
13. Was a subject in a previous cellulite clinical trial of collagenase clostridium histolyticum 
(CCH): AUX-CC-830, AUX-CC-831, EN3835-102, EN3835-104, EN3835-201, and/or 
EN3835-202 
14. Any other condition(s) that, in the Investigator’s opinion, might indicate the subject to be 
unsuitable for the study 
Investigational Product, Dosage and Mode of Administration:  
EN3835, 1.68 mg, subcutaneous. A dose of 0.84 mg of EN3835 per treatment area will be administered 
as 12 subcutaneous injections (0.3-mL injection administered as three 0.1-mL aliquots per injection) in 
each of two treatment areas for a total dose of 1.68 mg and a total volume of 7.2 mL (3.6 mL per 
treatment area). Total number of injections will be 24 injections per treatment visit into the assigned 
region (left and right buttocks or left and right posterolateral thighs). There will be 3 treatment visits at 
21-day intervals, ie, treatments on Days 1, 22, and 43 will be administered. 
Duration of Study: Up to 194 days (includes screening phase) 
Screening Phase: 
Up to 14 days 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Investigational Product: EN3835 
Name of Active Ingredient: Collagenase clostridium histolyticum 
Immunogenicity: Anti-AUX-I and anti-AUX-II antibody levels will be summarized using descriptive 
statistics for the actual value at the visit. Samples from Day 1 and Day 180 will be analyzed for 
anti-AUX-I and anti-AUX-II and a subset will be analyzed for neutralizing antibodies. 
Effectiveness Endpoints: 
 
Proportion at each level of improvement in the CR-PCSS of each assigned treatment area 
(Days 22, 43, 90, and 180): 
 
Proportion of responders defined as subjects with an improvement in severity from 
baseline of at least 2 levels of severity in the CR-PCSS 
 
Proportion of responders defined as subjects with an improvement in severity from 
baseline of at least 1 level of severity in the CR-PCSS 
 
Number of responses at each level of the subject satisfaction with cellulite treatment 
(Day 180)  
All effectiveness endpoints will be summarized as numbers and percentages. 
 

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Procedures 
Day -14 
to -1 
Screening 
Day 1 
(Baseline) 
Post-Injection Day 
Day 22 
(±3 d) 
Post-Injection Day 
Day 43 
(± 3 d) 
Post-Injection Day 
Day 90 
(± 7d) 
Day 180 
(+ 7 d) 
EOS/ 
ET 
 
1 
3 
6 
13 
1 
3 
6 
13 
1 
3 
6 
13 
Unsched. 
Visit 
 
Injection site reactions/local 
tolerability in assigned treatment 
areas 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Adverse events 
Monitored Throughout Study 
a Before injection. 
b Up to 4 hours before injection; approximately 15 and 30 minutes after injection. Pulse and BP to be taken after subject has been sitting for 5 minutes. Vital signs must be stable before the 
subject is discharged. 
c Applies only to sites participating in the photography sub-study. Photos are to be obtained before and after dimple marking on treatment visits. 
d Initial Hexsel CSS at Screening must be ≤13 on at least 2 bilateral treatment areas, and confirmed at Day 1 visit. 
e Assessment of each of the two assigned treatment areas only. 
f Serum pregnancy test on Screening and Day 180/EOS/ET, and any Unscheduled Visits; urine pregnancy test on Day 1, Day 22, Day 43, and Day 90 visits  
d=Days; ECG=Electrocardiogram; EFP=Edematous fibrosclerotic panniculopathy 
 

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6.
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF
FIGURES
TABLE OF CONTENTS 
1.
TITLE PAGE ................................................................................................................1
2.
SUMMARY OF CHANGES ........................................................................................2
3.
SPONSOR CONTACT INFORMATION ...................................................................3
4.
SYNOPSIS ...................................................................................................................4
5.
SCHEDULE OF EVENTS ...........................................................................................9
6.
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............11
7.
LIST OF ABBREVIATIONS .....................................................................................17
8.
INTRODUCTION ......................................................................................................18
8.1.
Background .................................................................................................................18
8.1.1.
Edematous Fibrosclerotic Panniculopathy .................................................................18
8.1.2.
Current EFP Treatments .............................................................................................18
8.1.3.
EN3835 (Collagenase Clostridium Histolyticum) ......................................................19
8.2.
Summary of Nonclinical Studies ................................................................................20
8.3.
Summary of Known Risks and Benefits .....................................................................20
8.4.
Rationale .....................................................................................................................21
9.
OBJECTIVES .............................................................................................................23
9.1.
Primary Objective .......................................................................................................23
9.2.
Secondary Objective ...................................................................................................23
9.3.
Exploratory Objectives ...............................................................................................23
10.
INVESTIGATIONAL PLAN .....................................................................................24
10.1.
Study Design ...............................................................................................................24
10.2.
Selection of Doses ......................................................................................................24
10.3.
Study Drug Administration .........................................................................................25
10.4.
Care Procedures After Injection .................................................................................27
10.5.
Discussion of Study Design, Including the Choice of Control Groups ......................27
11.
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................28
11.1.
Subject Inclusion Criteria ...........................................................................................28
11.2.
Subject Exclusion Criteria ..........................................................................................28
11.3.
Subject Discontinuation Criteria .................................................................................30

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11.3.1.
Replacement Procedures .............................................................................................30
12.
TREATMENT OF SUBJECTS ..................................................................................31
12.1.
Study Visits .................................................................................................................31
12.1.1.
Informed Consent .......................................................................................................31
12.1.2.
Subject Screening .......................................................................................................31
12.1.2.1.
Medical History ..........................................................................................................31
12.1.2.2.
Screening Period (Day -14 to Day -1) ........................................................................31
12.1.2.3.
Assignment of Treatment Areas .................................................................................32
12.2.
Selecting and Marking Dimples during Treatment ....................................................32
12.3.
Treatment Visit 1 (Day 1) ...........................................................................................33
12.3.1.
Treatment Visit 1: Pre-Injection .................................................................................33
12.3.2.
Treatment Visit 1: Injection and Post-injection ..........................................................34
12.4.
Follow-up Visits at 1, 3, 6, and 13 Days Following Each Treatment Visit ................34
12.4.1.
For Sites Participating in the Photographic Sub-study (section 12.12) ......................34
12.4.2.
For Sites not Participating in the Photographic Sub-study .........................................34
12.5.
Treatment Visit 2 (Day 22 [±3 days]) and Treatment Visit 3 (Day 43 [±3 
days]) ..........................................................................................................................34
12.5.1.
Treatment Visits 2 and 3: Pre-injection ......................................................................34
12.5.2.
Treatment Visits 2 and 3: Injection and Post-injection ..............................................35
12.6.
Day 90 (±3 days) ........................................................................................................35
12.7.
Day 180 (+7 days) End-of-Study / Early Termination ...............................................36
12.8.
Unscheduled Visits .....................................................................................................36
12.9.
Prior and Concomitant Medications and Procedures ..................................................36
12.9.1.
Prohibited Medications or Procedures ........................................................................36
12.10.
Treatment Compliance ................................................................................................37
12.11.
Blinding and Randomization ......................................................................................37
12.12.
Photographic Sub-study ..............................................................................................37
12.13.
Medical Status Follow-up ...........................................................................................37
13.
ASSESSMENT OF EFFECTIVENESS .....................................................................38
13.1.
Effectiveness Measurements ......................................................................................38
13.1.1.
Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) ....................38
13.1.2.
Subject Satisfaction with Cellulite Treatment Assessment ........................................38
13.1.3.
Hexsel Cellulite Severity Scale ..................................................................................39

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14.
ASSESSMENT OF SAFETY .....................................................................................41
14.1.
Definitions ..................................................................................................................41
14.1.1.
Adverse Events ...........................................................................................................41
14.1.2.
Serious Adverse Events ..............................................................................................41
14.2.
Monitoring Adverse Events ........................................................................................42
14.3.
Relationship to Study Drug ........................................................................................42
14.4.
Intensity Assessment ..................................................................................................43
14.5.
Reporting Adverse Events and Serious Adverse Events ............................................43
14.5.1.
Reporting Adverse Events ..........................................................................................43
14.5.2.
Reporting Serious Adverse Events .............................................................................43
14.5.2.1.
Follow-up Procedures for Serious Adverse Events ....................................................44
14.6.
Special Reporting Situations .......................................................................................44
14.6.1.
Adverse Events of Special Interest .............................................................................44
14.6.2.
Overdose/Misuse/Abuse .............................................................................................44
14.6.2.1.
Overdose .....................................................................................................................44
14.6.3.
Pregnancy ...................................................................................................................45
14.6.4.
AEs/SAEs Experienced by Non-subjects Exposed to Study Medication ...................45
14.7.
Clinical Laboratory Determinations ...........................................................................45
14.8.
Anti-AUX-I and Anti-AUX-II Antibodies .................................................................47
14.9.
Vital Signs ..................................................................................................................47
14.10.
Electrocardiogram .......................................................................................................47
14.11.
Physical Examination .................................................................................................48
14.12.
Other Safety Assessments ...........................................................................................48
15.
ASSESSMENT OF PHARMACOKINETICS ...........................................................49
16.
ASSESSMENT OF PHARMACODYNAMICS ........................................................50
17.
STATISTICAL CONSIDERATIONS AND METHODS .........................................51
17.1.
Determination of Sample Size ....................................................................................51
17.2.
Subject Populations ....................................................................................................51
17.2.1.
Safety Population ........................................................................................................51
17.2.2.
Effectiveness Population ............................................................................................51
17.2.3.
Per-Protocol (PP) Population ......................................................................................51
17.3.
Subject Disposition .....................................................................................................51
17.4.
Demographics and Other Baseline Characteristics .....................................................51

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17.5. 
Effectiveness Analyses ...............................................................................................52 
17.5.1. 
Effectiveness Variables ..............................................................................................52 
17.6. 
Safety Analyses ..........................................................................................................52 
17.6.1. 
Prior, Concomitant, and Follow-up Medication .........................................................52 
17.6.2. 
Study Drug Exposure ..................................................................................................52 
17.6.3. 
Measurement of Treatment Compliance ....................................................................53 
17.6.4. 
Adverse Events ...........................................................................................................53 
17.6.5. 
Vital Signs ..................................................................................................................53 
17.6.6. 
Clinical Laboratory Parameters ..................................................................................54 
17.6.7. 
Electrocardiogram .......................................................................................................54 
17.6.8. 
Physical Examination .................................................................................................54 
17.6.9. 
Other Safety Measurements ........................................................................................54 
17.7. 
Pharmacokinetic Analyses ..........................................................................................54 
17.8. 
Pharmacodynamic Analyses .......................................................................................54 
17.9. 
Other Data (eg, Health Economics/QOL, Pharmacogenetic, etc.) .............................54 
17.10. 
Interim Analysis ..........................................................................................................54 
17.11. 
Statistical Software .....................................................................................................54 
18. 
STUDY DRUG MATERIALS AND MANAGEMENT ...........................................55 
18.1. 
Study Drug Identity ....................................................................................................55 
18.2. 
Study Drug Packaging and Labeling ..........................................................................55 
18.3. 
Study Drug Storage .....................................................................................................55 
18.4. 
Study Drug Preparation ..............................................................................................55 
18.5. 
Study Drug Accountability .........................................................................................56 
18.5.1. 
Study Drug Handling and Disposal ............................................................................56 
19. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS .........................................57 
19.1. 
Source Documents ......................................................................................................57 
19.2. 
Study Monitoring ........................................................................................................57 
19.3. 
Audits and Inspections ................................................................................................57 
19.4. 
Institutional Review Board (IRB) ...............................................................................57 
19.5. 
Data Recording and Documentation ...........................................................................57 
20. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................58 
21. 
ETHICS ......................................................................................................................59 
21.1. 
Ethics Review .............................................................................................................59 

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21.2.
Ethical Conduct of the Study ......................................................................................59
21.3.
Subject Information and Consent ...............................................................................60
22.
DATA HANDLING AND RECORDKEEPING .......................................................61
22.1.
Data Collection ...........................................................................................................61
22.2.
Study Documentation .................................................................................................61
23.
REPORTING AND PUBLICATION .........................................................................62
24.
INVESTIGATOR OBLIGATIONS ...........................................................................63
24.1.
Regulatory Documents ...............................................................................................63
24.2.
Delegation of Responsibilities and Adequate Resources ...........................................64
24.3.
Medical Care of Study Subjects .................................................................................64
24.4.
Use of Investigational Materials .................................................................................64
24.5.
Retention of Records ..................................................................................................64
24.6.
Subject Confidentiality ...............................................................................................65
25.
TERMINATION OF STUDY ....................................................................................66
26.
INVESTIGATOR’S STATEMENT ...........................................................................67
27.
REFERENCES ...........................................................................................................68
APPENDIX A.
DOCUMENTS REQUIRED PRIOR TO INITIATION OF THE 
STUDY ..............................................................................................................69
APPENDIX B.
CLINICIAN-REPORTED PHOTONUMERIC CELLULITE 
SEVERITY SCALE (CR-PCSS) FOR THE BUTTOCK .................................71
APPENDIX C.
CLINICIAN-REPORTED PHOTONUMERIC CELLULITE 
SEVERITY SCALE (CR-PCSS) FOR THE THIGH .......................................72
APPENDIX D.
HEXSEL DM, DAL’FORNO T, HEXSEL CL. A VALIDATED 
PHOTONUMERIC CELLULITE SEVERITY SCALE. J EUR ACAD 
DERMATOL VENEREOL. 2009;23(5):523-8 ...................................................73
APPENDIX E. REFERENCE IMAGES FOR HEXSEL SEVERITY RATINGS .....................80

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LIST OF TABLES 
Table 1:
Sponsor Contact Information ........................................................................................3
Table 2:
Abbreviations and Special Terms ...............................................................................17
Table 3: 
Study Treatment Groups .............................................................................................24
Table 4:
Concomitant Medication Restrictions for Subjects During the Treatment 
Phase of Study ............................................................................................................37
Table 5:
Subject Satisfaction with Cellulite Treatment Assessment - Buttocks .......................38
Table 6:
Subject Satisfaction with Cellulite Treatment Assessment - Thighs ..........................39
Table 7:
Hexsel Cellulite Severity Scale ..................................................................................40
Table 8:
Clinical Laboratory Tests ...........................................................................................46
Table 9:
Vital Signs Measurements on Injection Day ..............................................................47
Table 10:
Fitzpatrick Scale .........................................................................................................48
LIST OF FIGURES 
Figure 1:
Study Design ...............................................................................................................24
Figure 2:
Study Drug Administration at Each Injection Site .....................................................26
Figure 3:
Examples of Subject Dimple and Injection Site Markings .........................................33

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7. 
LIST OF ABBREVIATIONS  
The following abbreviations and special terms are used in this study protocol. 
Table 2: 
Abbreviations and Special Terms 
Abbreviation 
Definition 
AE 
Adverse event 
AUX-I 
Clostridial class I collagenase 
AUX-II 
Clostridial class II collagenase 
BMI 
Body mass index 
CRF 
Case report form 
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 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HREC 
Human Research Ethics Committee 
IB 
Investigator brochure 
ICF 
Informed consent form 
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 
LOCF 
Last Observation Carried Forward 
PR-PCSS 
Patient-Reported Photonumeric Cellulite Severity Scale 
Qualified designee 
Qualified by education and training to perform the study procedure 
(eg, sub-Investigator, nurse). 
Region 
Bilateral buttocks or bilateral thighs (each consisting of 2 treatment areas, ie, 
left/right buttock or left/right thigh). To be suitable for treatment, the region 
must have an Investigator CR-PCSS score of 2 or higher and a Hexsel CSS 
score of no greater than 13 at the Screening visit. 
SAE 
Serious Adverse Event 
S-GAIS 
Subject – Global Aesthetic Improvement Scale 
TEAE 
Treatment-emergent adverse event. Adverse events that occur on or after the 
first injection of study drug. 
Treatment area 
Left buttock, right buttock, left thigh, or right thigh.  
 

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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. 
This creates an uneven surface with dimpling.(1) 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 kiloDaltons (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 degrees 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 posterolateal thigh or a right 
posterolateral thigh) of cellulite with EN3835 0.84mg 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 the Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS), 
Patient Reported Photonumeric Cellulite Severity Scale (PR-PCSS), Investigator Global 
Aesthetic Improvement Scale (I-GAIS), Subject Global Aesthetic Improvement Scale (S-GAIS), 
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 treated quadrant as assessed by the primary endpoint 
of 2-level composite responder analyses, the proportion of responders based on an improvement 
of ≥2 level 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 
sixty-two percent (62.9%) of subjects in the EN3835 0.84mg 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 four 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 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 100% 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 0.84mg in 
11 female subjects with EFP showed that there was no quantifiable levels of AUX-I or AUX-II 
at any timepoint after subcutaneous injection of EN3835 0.84mg into one quadrant. A second 
Phase 1, open-label, safety and pharmacokinetic study of a single dose of EN3835 0.84mg per 
treatment area in two treatment areas (buttock-buttock, thigh-thigh, or buttock-thigh) 
concurrently (total dose of 1.68mg) showed that there was no quantifiable levels of AUX-I or 
AUX-II at any timepoint post-dose attributable to the injection of EN3835 1.68mg. 
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 
discolouration (3.2%), and injection site erythema (2.1%). These events are similar to events 
reported in the clinical trials of EN3835 for the approved indications. Post-marketing safety data 
have been consistent with data reported in clinical trials. 

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Although a thorough benefit of EN3835 has not been fully evaluated in the treatment of EFP, the 
efficacy results from the Phase 2b study and previous EFP studies warranted further 
development. 
8.4. 
Rationale 
The alterations found in EFP are due largely to fibrosis of the connective tissues in the dermis 
and/or subcutaneous tissues.(2) Subcutaneous fat lobes are separated from one another by thin, 
usually rigid strands of connective tissues, which cross the fatty layers and connect the dermis to 
the underlying fascia. These collagen septae stabilize the subcutis and divide the fat. Shortening 
and thickening of the septae due to fibrosis provokes retraction at the insertion points of the 
trabeculae, causing the depressions that characterize EFP.(2) 
The pharmacologic activity of EN3835 involves selective lysis of the triple-helical region of 
collagen under physiological conditions at the site of injection. EN3835 targets the collagenase 
structural matrix (eg, septae), which is the underlying cause of the skin dimpling, and does not 
require systemic exposure to be effective. The pharmacologic activity of EN3835 is local, rapid, 
and is essentially complete within 24 hours. 
The data from the Phase 2a EFP dose-ranging study (AUX-CC-831) suggest that EN3835 
0.84 mg was effective in the treatment of EFP based on improvement in the severity of cellulite 
as determined by both the Investigator and the subject, although the EN3835 0.48 mg group did 
show improvement in some of the efficacy parameters. 
 There were no safety concerns following administration of up to 3 treatment sessions 
of EN3835 0.84 mg in the treatment of EFP (section 5.3.1.3). The safety profile of 
EN3835 0.84 mg in the treatment of EFP was similar to that observed in the EN3835 
0.06 mg group and the EN3835 0.48 mg group. No notable differences were observed 
across the 3 treatment groups. 
 Safety findings from the Phase 2a EFP dose-ranging study are similar to that 
observed in previous clinical studies with XIAFLEX in the treatment of Dupuytren’s 
contracture and Peyronie’s disease, in that that the majority of AEs occurred at the 
site of injection and resolved before the next scheduled treatment. 
 The immunogenicity profile of EN3835 in the Phase 2a EFP dose-ranging study is 
similar to that observed in the Dupuytren’s contracture and Peyronie’s disease 
programs. 
 Based on the efficacy and safety findings from the Phase 2a EFP dose-ranging study, 
the EN3835 0.84-mg dose was carried forward to this study. 
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 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 

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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 a region (buttocks or posterolateral thighs) warranted further 
investigation in this study. 
Treating two bilateral treatment areas of a region at each treatment visit will potentially provide a 
symmetrical-like improvement in appearance. Support for evaluation of the treatment of two 
treatment areas concurrently is based on: 1) the safety findings from the previous EFP studies are 
local to the injection site, 2) the pharmacological activity of EN3835 is local and does not require 
systemic exposure, and 3) no significant quantifiable systemic concentration has been 
attributable to injection of two buttocks concurrently. 
The integration of dose and use justification supports this study of evaluation of EN3835 
0.84-mg per treatment area in two treatment areas (a region) concurrently. 

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9. 
OBJECTIVES 
9.1. 
Primary Objective 
The primary objective of this study is to assess the safety of EN3835 in the treatment of 
edematous fibrosclerotic panniculopathy (EFP) commonly known as cellulite in adult women. 
9.2. 
Secondary Objective 
The secondary objective of this study is to assess the effectiveness of EN3835 in the treatment of 
edematous fibrosclerotic panniculopathy (EFP) commonly known as cellulite 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 study will be performed at approximately 10 study centers located in the United States. This 
clinical study will be conducted as a multicenter, open-label study of EN3835 in adult women 
with EFP. The study will consist of 3 treatment visits, 21 days apart. Subjects meeting the entry 
criteria for this study will receive EN3835 treatment within an investigational site and assigned 
region (ie, bilateral buttocks or bilateral thighs) on Day 1, Day 22, and Day 43, and will be 
followed for up to 180 days from the first day of treatment. Subjects will receive follow-up visits 
at 1, 3, 6, and 13 days after each treatment course (either by phone or, for subjects participating 
in the photographic sub-study, in the clinic), and 2 follow-up visits at Day 90 and Day 180 to 
assess treatment effectiveness. The study also includes a photographic sub-study (conducted at 
two sites) in which subjects will return to the clinic for photographs at 1, 3, 6, and 13 days after 
each treatment course to coincide with the follow up visits. Sites participating in the 
photographic sub-study will also follow subjects for the same 180-day period. 
The complete schedule of events is provided in section 5. 
Figure 1: 
Study Design 
 
Table 3:  
Study Treatment Groups 
Dose per 
Each Injectiona / 
Number of 
Subjects 
Injection 
Volume per 
Each 
Injection 
Number of 
Injections at Each 
Treatment Visit 
Dose (mg) at Each 
Treatment Visit 
Injection 
Volume (mL) 
per Each 
Treatment 
Visit 
 
Cumulative EFP 
Dose 
EN3835 0.07 mg/ 
N=up to 150 
0.3 mL 
12 per treatment 
area x 2 treatment 
areas = 24 
0.84 mg per 
treatment area x 2 
treatment areas = 
1.68 mg 
(12 injections per 
treatment area x 
0.07 mg/injection x 
2 treatment areas) 
3.6 mL per 
treatment area 
x 2 treatment 
area = 7.2 mL 
(24 injections 
× 0.3 mL) 
5.04 mg 
(3 treatment visits × 
0.84 mg per 
treatment area x 2 
treatment areas) 
a Each injection of study drug is 0.3 mL administered as three 0.1 mL aliquots. 
10.2. 
Selection of Doses 
The dose of EN3835 chosen for this study was based on the experience from earlier studies. 

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The data from the Phase 2a EFP dose-ranging study (AUX-CC-831) suggest that EN3835 
0.84 mg is most effective in the treatment of EFP based on improvement in the severity of 
cellulite as determined by both the Investigator and the subject, although the EN3835 0.48-mg 
group did show improvement in some of the efficacy parameters. 
 There were no safety concerns following administration of up to 3 treatment visits of 
EN3835 0.84 mg in the treatment of EFP (AUX-CC-831 CSR). The safety profile of 
EN3835 0.84 mg in the treatment of EFP was similar to that observed in the EN3835 
0.06-mg group and the EN3835 0.48-mg group. No notable differences were 
observed across the 3 treatment groups. 
 Safety findings from the Phase 2a EFP dose-ranging study are similar to that 
observed in previous clinical studies with XIAFLEX in the treatment of Dupuytren’s 
contracture and Peyronie’s disease, in that the majority of AEs occurred at the site of 
injection and resolved before the next scheduled treatment. 
 The immunogenicity profile of EN3835 in the Phase 2a EFP dose-ranging study is 
similar to that observed in the Dupuytren’s contracture and Peyronie’s disease 
programs. 
 Based on the efficacy and safety findings from the Phase 2a EFP dose-ranging study, 
the EN3835 0.84-mg dose was carried forward to a Phase 2b study (EN3835-201). 
The results from the Phase 2b EFP study (EN3835-201) further suggested that EN3835 0.84 mg 
is an effective treatment of EFP based on improvement in the severity of cellulite as determined 
by the Investigator and the subject. There were no safety concerns following EN3835 0.84 mg 
in the treatment of EFP (section 8.4). Safety findings from the Phase 2b EFP study are similar to 
that observed in previous clinical studies with XIAFLEX in the treatment of Dupuytren’s 
contracture and Peyronie’s disease, in that that the majority of AEs occurred at the site of 
injection and resolved before the next scheduled treatment. The immunogenicity profile of 
EN3835 in the Phase 2b EFP study is similar to that observed in the Dupuytren’s contracture 
and Peyronie’s disease programs. 
Based on the efficacy and safety findings from the Phase 2a and 2b EFP studies, the EN3835 
0.84-mg dose per treatment area was carried forward to this study. The findings from previous 
studies that the majority of adverse events after EN3835 treatment are local to the injection site 
and that there is no quantifiable systemic exposure observed after concurrent treatment of two 
treatment areas (total dose of 1.68 mg) supports the proposed study to evaluate EN3835 
treatment of two treatment areas. 
10.3. 
Study Drug Administration 
Study drug will be injected subcutaneously while the subject is in a prone position using a 
syringe with a 30-gauge ½-inch needle. Each injection site will receive a single skin injection of 
study drug administered as three 0.1-mL aliquots to Positions A, B, and C (for a total injection 
volume of 0.3 mL) as shown in 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. 

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NOTE: EN3835 is a foreign protein and Investigators should be prepared to address and manage 
an allergic reaction should it occur. At the time of each injection, a 1:1,000 solution of 
epinephrine for injection, 50-mg diphenhydramine injection or a suitable equivalent, and oxygen 
must be available with the Investigator and site staff must be familiar with their use. 
10.4. 
Care Procedures After Injection 
To evaluate the subject for possible immediate immunological AEs, the subject will remain in 
direct observation of medical personnel who are skilled in the management of an allergic 
reaction for 30 minutes after receiving the injection of study drug and until the subject exhibits 
no sign of an immunological or other clinically significant systemic or local AE. The subject’s 
vital signs should be stable before the subject can leave direct observation (see section 14.9). 
The Investigator or qualified designee will then apply a sterile dressing to the injection areas 
with hypoallergenic tape. The subject will be instructed to remove the dressing in the evening. 
10.5. 
Discussion of Study Design, Including the Choice of Control Groups 
The design of this study was based on the primary objective to assess the safety of EN3835 
0.84 mg per treatment area in the concurrent treatment (total dose of 1.68 mg) of EFP in a 
treatment region (bilateral buttocks or bilateral posterolateral thigh) in adult women. It is an 
open-label study. 

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11. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
11.1. 
Subject Inclusion Criteria 
In order to be eligible to participate in the study, subjects must meet the following criteria: 
1. Voluntarily sign and date an informed consent agreement 
2. Be a female ≥18 years of age 
3. At Screening visit, have at least 2 bilateral treatment areas with each treatment area 
having: 
a. a score of 2 (mild) or greater as reported by the Investigator (CR-PCSS), and 
b. a Hexsel CSS score no greater than 13 
4. Be willing to apply sunscreen to the selected treatment areas before each exposure to the 
sun while participating in the study (ie, Screening through end-of-study) 
5. Be judged to be in good health, based upon the results of a medical history, physical 
examination, and laboratory profile at Screening 
6. 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 
7. Be willing and able to cooperate with the requirements of the study 
8. Be able to read, complete, and understand the patient-reported outcomes rating 
instruments in English 
11.2. 
Subject Exclusion Criteria 
Subjects who meet any of the following criteria will not be eligible to participate in the study: 
1. Has any of the following systemic conditions: 
a. Coagulation disorder 
b. Evidence or history of malignancy (other than excised basal-cell carcinoma) unless 
there has been no recurrence in at least 5 years 
c. History of keloidal scarring or abnormal wound healing 
d. Concurrent diseases or conditions that might interfere with the conduct of the study, 
confound the interpretation of the study results, or endanger the subject’s well-being. 
Any questions about concurrent diseases should be discussed with the Medical 
Monitor. 
e. Evidence of clinically significant abnormalities on physical examination, vital signs, 
electrocardiogram (ECG), or clinical laboratory values 

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

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11.3. 
Subject Discontinuation Criteria 
A premature discontinuation will occur when a subject who signed informed consent ceases 
participation in the study, regardless of circumstances, prior to the completion of the protocol. 
Subjects can be prematurely discontinued from the study for one of the following reasons: 
 An adverse event 
 A protocol violation (reason must be specified, for example: lack of compliance, use 
of a prohibited concomitant medication, failure to meet inclusion/exclusion criteria 
after study entry, etc.) 
 Withdrawal by subject (reason must be specified) 
 The subject was “lost to follow-up” 
 Other reasons (reason must be specified, for example: the subject moved, pregnancy, 
Investigator decision, Sponsor decision to terminate trial, etc.) 
If a subject discontinues from the study, all end-of-study procedures should be conducted as 
detailed in section 5, Schedule of Events. 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 are required (but 
are encouraged to reduce missing information) except the collection of adverse event (AE) 
information. This information should be recorded in the source documentation and the eCRF. 
11.3.1. 
Replacement Procedures 
Subjects who discontinue from the study will not be replaced. 

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

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4. After the Investigator has completed the CR-PCSS rating, the Investigator will conduct 
live cellulite evaluation of the 4 treatment areas using the Hexsel CSS. The ratings from 
the CR-PCSS and Hexsel CSS (section 13.1.3 ) will be used to assess initial eligibility of 
treatment areas for study entry. 
5. If eligible based on CR-PCSS, and Hexsel CSS ratings, random assignment of a 
treatment region (two bilateral treatment areas) for treatment (section 12.1.2.3) 
6. Medical history including EFP history (section 12.1.2.1) 
7. Record prior and concomitant medications/procedures (section 12.9) 
8. Physical examination including measurement of body weight, height, Fitzpatrick skin 
type (section 14.11) 
9. Vital sign measurements (section 14.9) 
10. 12-lead electrocardiogram (ECG) (section 14.10) 
11. Collection of samples for: 
a. Clinical laboratory testing (section 14.7) 
b. Serum pregnancy testing (section 14.7) 
12. Adverse events (section 14) 
12.1.2.3. Assignment of Treatment Areas 
Subjects must have at least 1 eligible treatment region (eg, 2 bilateral treatment areas) that meet 
the following criteria for inclusion into the study: 
 CR-PCSS score of 2 or greater in each treatment area, and 
 Hexsel CSS score no greater than 13 in either treatment area. 
Assignment of the treatment region will be chosen randomly by the interactive web response 
system (IWRS) from the regions meeting the above inclusion criteria. If no two bilateral 
treatment areas meet the criteria, the IWRS will inform the site that the subject does not have 
treatment regions that qualify for the study. 
12.2. 
Selecting and Marking Dimples during Treatment 
Selection of dimples to be treated in the two assigned treatment areas is at the discretion of the 
Investigator. Dimples must be well-defined and evident when the subject is standing in a 
consistent relaxed pose (without the use of any manipulation such as skin pinching or muscle 
contraction). Each subject will receive 3 treatment visits of study drug unless the treatment area 
is dimple-free (score of 0 on CR-PCSS as reported by the Investigator). 
Treatment consists of 12 injections per treatment area (total 24 injections) per visit. Because the 
goal of treatment is to improve the aesthetic appearance of each entire treatment area, the 
Investigator will be instructed to select dimples that in his/her opinion would most improve the 
aesthetic appearance of each entire treatment area. The same dimples within a treatment area or 
different dimples within a treatment area may be treated at each visit but injections must all be 
within the assigned treatment area for all 3 visits. Each treatment area will receive all 3 treatment 

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visits unless the assigned treatment area has no treatable EFP dimples and the Investigator rates 
the treatment area a score of 0 on the CR-PCSS. If no injections in a particular treatment area are 
given at Treatment Visit 2, subjects will still be assessed for treatment in the contralateral 
treatment area at Treatment Visit 2, and will return for the Day 43 visit and the assigned 
treatment areas will again be evaluated by the Investigator (CR-PCSS). If the Investigator rates 
either or both of the assigned treatment areas greater than 0 on the CR-PCSS, injections at 
Treatment Visit 3 should be given. 
At each treatment visit, prior to selecting and marking dimples, sites participating in the 
photography sub-study should photograph the selected treatment areas. For each dimple selected 
for treatment, the Investigator or qualified designee will choose injection sites (injection sites 
within a dimple should be spaced approximately 2 cm apart, if a dimple requires more than 
1 injection; locating at least one injection site at the nadir, if present, of the dimple). Each 
injection site will be marked with a “dot” using a surgical marker. For round dimples, the “dot” 
will be placed in the center of the dimple; for elongated dimples, “dots” will be spaced out 
approximately 2 cm along the longer axis of the dimple. The Investigator or qualified designee 
will then use a surgical marker to circle each of the dimples selected for treatment. Circles in the 
assigned treatment area should not overlap (Figure 3). Sites participating in the photographic 
sub-study (section 12.12) will be instructed to obtain photographs of the subject’s marked 
treatment areas prior to injection on the visit days that require treatment (section 5). 
Figure 3: 
Examples of Subject Dimple and Injection Site Markings 
Sample Thigh Marking 
Sample Buttock Marking 
 
12.3. 
Treatment Visit 1 (Day 1) 
12.3.1. 
Treatment Visit 1: Pre-Injection 
1. For eligible treatment areas, obtain kit numbers of study treatment and reconstitute drug 
product using aseptic technique 
2. Record concomitant medications/procedures (section 12.9) 
3. Vital sign measurements (section 14.9) 

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4. Collection of samples for: 
a. Anti-AUX-I and anti-AUX-II antibody testing (section 14.8) 
b. Urine pregnancy testing (section 14.7) 
5. Digital photographs of each treatment area before marking dimples and injection sites 
(NOTE: This is ONLY for sites participating in the photographic sub-study.) 
6. Select and mark dimples to be treated in each of the assigned treatment areas 
(section 12.2) 
7. Digital photographs of each treatment area after marking dimples and injection sites 
(section 12.12) 
12.3.2. 
Treatment Visit 1: Injection and Post-injection 
1. Administration of study drug in the prone position (section 10.3) 
2. Record number of dimples treated and number of injections administered in each of the 
two assigned treatment areas 
3. Vital sign measurements (section 14.9) 
4. Injection site reactions and local tolerability 
5. Adverse events (section 14) 
12.4. 
Follow-up Visits at 1, 3, 6, and 13 Days Following Each Treatment 
Visit 
12.4.1. 
For Sites Participating in the Photographic Sub-study (section 12.12) 
1. Any changes in concomitant medications or procedures 
2. Injection site reactions and local tolerability 
3. Adverse events (section 14) 
4. Digital photographs of each treatment area 
12.4.2. 
For Sites not Participating in the Photographic Sub-study 
1. Any changes in concomitant medications or procedures 
2. Injection site reactions and local tolerability 
3. Adverse events (section 14) 
12.5. 
Treatment Visit 2 (Day 22 [±3 days]) and Treatment Visit 3 (Day 43 
[±3 days]) 
12.5.1. 
Treatment Visits 2 and 3: Pre-injection 
1. Record concomitant medications/procedures (section 12.9) 
2. Body weight measurement 

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3. Vital sign measurements (section 14.9) 
4. Collection of samples for: 
a. Anti-AUX-I and anti-AUX-II antibody testing (section 14.8) 
b. Urine pregnancy testing (section 14.7) 
5. Digital photographs of each treatment area before marking dimples and injection sites 
(NOTE: This is ONLY for sites participating in the photographic sub-study.) 
6. Investigator Cellulite Assessments of each of the assigned treatment areas prior to 
marking dimples and injection sites using: 
a. Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) live assessment 
of subject (section 13.1.1) 
7. Select and mark dimples to be treated in each assigned treatment areas (section 12.2) 
8. Digital photographs of each buttock after marking dimples and injection sites 
(section 12.12) 
12.5.2. 
Treatment Visits 2 and 3: Injection and Post-injection 
1. For eligible assigned treatment area(s), obtain kit number(s) of study treatment and 
reconstitute drug product using aseptic technique. 
2. Administration of study drug in the prone position (section 10.3) 
3. Record number of dimples treated and number of injections administered in each 
assigned treatment area 
4. Vital sign measurements (section 14.9) 
5. Injection site reactions and local tolerability 
6. Adverse events (section 14) 
12.6. 
Day 90 (±3 days) 
The following procedures will be performed on Day 90: 
1. Record concomitant medications/procedures (section 12.9) 
2. Measurement of body weight 
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. Investigator Cellulite Assessments of each of the assigned treatment areas using: 
a. Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) live assessment 
of subject (section 13.1.1) 

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6. Injection site reactions and local tolerability 
7. Adverse events (section 14) 
12.7. 
Day 180 (+7 days) End-of-Study / Early Termination 
The following procedures will be performed on Day 180: 
1. Measurement of body weight 
2. Vital sign measurements (section 14.9) 
3. Collection of samples for: 
a. Clinical laboratory testing (section 14.8) 
b. Anti-AUX-I and anti-AUX-II antibody testing (section 14.7) 
c. Serum pregnancy testing (section 14.7) 
4. Subject Cellulite Assessment using: 
a. Subject Satisfaction with Cellulite Treatment Assessment (section 13.1.2) 
5. Investigator Cellulite Assessments of each of the assigned treatment areas using: 
a. Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) live assessment 
of subject (section 13.1.1) 
6. Injection site reactions and local tolerability 
7. Adverse events (section 14) 
12.8. 
Unscheduled Visits 
If any subject needs to return to the site prior to her next scheduled visit, site staff should follow 
the Unscheduled Visit procedures outlined in section 5. Site staff may conduct additional study 
procedures if required. 
12.9. 
Prior and Concomitant Medications and Procedures 
All prior medications taken within 90 days before Day 1 will be recorded. All medications 
(including over-the-counter medications) taken by the subject on Day 1 through the end of the 
study must be recorded. Any prior treatments (medications or procedures) for EFP through the 
end of the study must be recorded on the appropriate eCRF page. 
Additionally, any diagnostic, therapeutic or surgical procedures performed during the study 
period should be recorded including the date, indication for and description of the procedure. 
12.9.1. 
Prohibited Medications or Procedures 
The following medications are prohibited for randomized subjects during the study: 
anticoagulants (warfarin, heparin, direct thrombin inhibitors, Factor X inhibitors) and antiplatelet 
agents (aspirin >150 mg/day and P2Y12 inhibitors, such as clopidogrel), which can cause 
additional bruising. However the use of aspirin at a dose level of ≤150 mg per day will be 
permitted during study. 

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Procedures listed in exclusion criterion #4 (section 11.2, Exclusion Criterion# 4) are prohibited 
for subjects during the study. 
Table 4: 
Concomitant Medication Restrictions for Subjects During the Treatment 
Phase of Study 
Drug Class 
Restrictions 
Anticoagulants 
Subjects cannot take antiplatelet agents or anticoagulants (except for ≤150 mg aspirin daily) 
within 7 days before and 7 days after the dosing administration. 
12.10. 
Treatment Compliance 
Subjects will receive study drug administered by an Investigator at the Investigator’s site.  
Accidental or intentional overdoses should be reported to the Sponsor/designee promptly (see 
section 14.6.2.1, Overdose). 
12.11. 
Blinding and Randomization 
This is an open-label study. Each subject will have one or two regions (bilateral buttocks and/or 
thighs) eligible for treatment. If two regions are eligible, the IWRS will randomly assign each 
subject a treatment region. 
12.12. 
Photographic Sub-study 
Two (2) or more sites will participate in a photographic sub-study designed to capture 
photographic records of subjects’ progression through the study treatment. In the sub-study, the 
treatment areas will be photographed before and after dimple marking while the subject is 
standing in a consistent relaxed pose as described in the Photography Manual. Subjects will be 
instructed to return to the clinic for follow-up photographs at 1, 3, 6, and 13 days after each 
treatment visit. 
12.13. 
Medical Status Follow-up 
Subjects will be contacted (either by telephone, or in person for subjects participating in the 
Photographic Sub-study) at 1, 4, 8, and 14 days after each treatment visit to provide updates on 
their medical status following treatment. Specific updates to medical status will include: 
1. Any changes in concomitant medications or procedures 
2. Injection site reactions and local tolerability 
3. Adverse events (section 14) 

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13. 
ASSESSMENT OF EFFECTIVENESS 
13.1. 
Effectiveness Measurements 
13.1.1. 
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 or thigh; there are separate scales for buttocks or thighs. The scales are 5-level 
photonumeric scales developed specifically for clinicians and used by the Investigator to assess 
the severity of the subject’s cellulite in each treatment area by live assessments; the ratings range 
from 0 (None) to 4 (Severe) with labels and descriptors to aid the Investigator in the assessments. 
Investigators will be trained and qualified on the use of the CR-PCSS prior to assessing any 
subjects. 
At the Screening visit, the Investigator will determine severity of cellulite of each of the 
4 treatment areas by assessing subjects using the CR-PCSS for buttock (Appendix B) or thigh 
(Appendix C). Before injections on treatment visits Day 1, Day 22, and Day 43, and on visit 
Day 90 and Day 180, Investigators will evaluate each of the two assigned treatment areas via live 
assessment. If the buttocks are the treated region, the Investigator will use the CR-PCSS for the 
buttock to make his/her evaluation; if the thighs are the treated region, the Investigator will use 
the CR-PCSS for the thigh to make his/her evaluation. 
13.1.2. 
Subject Satisfaction with Cellulite Treatment Assessment 
At the Day 180 visit, subjects will be instructed to answer a question related to their treated 
region. Subjects will be given one list of region-specific responses based on which region was 
treated and they will provide a rating from those below that best represents their answer. 
For subjects that had buttocks treated: 
Today, how satisfied are you with the results of the cellulite treatment you received on the 
specific area or areas on your buttocks that were treated? 
Table 5: 
Subject Satisfaction with Cellulite Treatment Assessment - Buttocks 
Rating 
Description 
+2 
I am very satisfied with the cellulite treatment on my buttocks. 
+1 
I am satisfied with the cellulite treatment on my buttocks. 
0 
I am neither dissatisfied nor satisfied with the cellulite treatment on my buttocks. 
-1 
I am dissatisfied with the cellulite treatment on my buttocks. 
-2 
I am very dissatisfied with the cellulite treatment on my buttocks. 
Or 

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For subjects that had thighs treated: 
Today, how satisfied are you with the results of the cellulite treatment you received on the 
specific area or areas on your thighs that were treated? 
Table 6: 
Subject Satisfaction with Cellulite Treatment Assessment - Thighs 
Rating 
Description 
+2 
I am very satisfied with the cellulite treatment on my thighs. 
+1 
I am satisfied with the cellulite treatment on my thighs. 
0 
I am neither dissatisfied nor satisfied with the cellulite treatment on my thighs. 
-1 
I am dissatisfied with the cellulite treatment on my thighs. 
-2 
I am very dissatisfied with the cellulite treatment on my thighs. 
13.1.3. 
Hexsel Cellulite Severity Scale 
The Hexsel Cellulite Severity Scale (referred to as the Hexsel CSS) is a photonumeric scale that 
looks at 5 key morphologic features of cellulite: (A) number of evident depressions, (B) depth of 
depressions, (C) morphological appearance of skin surface alterations, (D) laxity, flaccidity or 
sagging of skin, and (E) current classification scale based on medical literature including 
Nürnberger and Müller.(12,13) Each of these features is evaluated on a 4-level scale from a low 
of 0 to a high of 3 as described in Table 7 (Appendix D and Appendix E). The total score is the 
summation of all 5 features. 
The Investigator or qualified designee will independently use the Hexsel CSS to assess the 
severity of EFP in each of the 4 treatment areas at the Screening visit and each of the two 
assigned treatment areas on Day 1. All cellulite assessments should be made while the subject is 
in the standing position with relaxed gluteus muscles. However, when evaluating the subject for 
Category E (classification scale by Nürnberger and Müller) (13) if the subject has no evident 
depressions, the subject should be asked to contract her gluteus muscles or the pinch test should 
be applied (by pinching the skin between the thumb and index finger) so the Investigator or 
qualified designee can differentiate between scores/grades of zero (0) or I. 

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Table 7: 
Hexsel Cellulite Severity Scale 
A 
Number of evident depressions 
0=none/no depressions 
1=a small amount: 1-4 depressions are visible 
2=a moderate amount: 5-9 depressions are visible 
3=a large amount: 10 or more depressions are visible 
B 
Depth of depressions 
0=no depressions 
1=superficial depressions 
2=medium depth depressions 
3=deep depressions 
C 
Morphological appearance of skin 
surface alterations 
0=no raised areas 
1=‘orange peel’ appearance 
2=‘cottage cheese’ appearance 
3=‘mattress’ appearance 
D 
Grade of laxity, flaccidity, or sagging 
skin 
0=absence of laxity, flaccidity, or sagging skin 
1=slight draped appearance 
2=moderate draped appearance 
3=severe draped appearance 
E 
Classification scale by Nürnberger and 
Müllera 
0 = zero grade = Grade or Stage 0 = There is no alteration of the 
skin surface. 
1 = first grade = Grade or Stage I = The skin of the affected area is 
smooth while the subject is standing or lying, but the alterations to 
the skin surface can be seen by pinching the skin or with muscle 
contraction. 
2= second grade = Grade or Stage II = The orange skin or mattress 
appearance is evident when standing, without the use of any 
manipulation (skin pinching or muscle contraction). 
3= third grade = Grade or Stage III = The alterations described in 
Grade or Stage II, are present together with raised areas and 
nodules. 
Source: Hexsel DM, Dal’Forno T, Hexsel CL. A validated photonumeric cellulite severity scale. J Eur Acad 
Dermatol Venereol. 2009;23(5):523-8. 
a Subjects should be evaluated in the standing position with relaxed gluteus muscles. However, if the subject has no 
evident depressions, they should be asked to contract their gluteus muscles or the pinch test should be applied (by 
pinching the skin between the thumb and index finger) in order to differentiate between grade/stage of zero (0) 
or I. 

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

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

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

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

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Clinical laboratory test data will be reviewed by the Investigator, or designee, and additional 
clinical laboratory tests may be ordered at his/her discretion (eg, if the results of any clinical 
laboratory test falls outside the reference range or clinical symptoms necessitate additional 
testing to ensure safety). Any additional testing will be performed by the designated central 
laboratory. The Investigator or qualified designee must acknowledge the review of laboratory 
results. 
The Investigator will review all abnormal lab results for potentially clinically important. Any 
abnormal clinical laboratory test result meeting the Investigator’s criteria for potentially 
clinically important (refer to central laboratory manual) will be recorded as an AE or SAE as 
appropriate (see section 14.1.1, Adverse Events, and section 14.1.2, Serious Adverse Events). 
Laboratory results will be sent electronically to Endo Pharmaceuticals Inc. for data management. 
Clinical laboratory parameters that will be measured in this study are listed in Table 8. 
Table 8: 
Clinical Laboratory Tests 
Hematology 
Biochemistry 
Urinalysis 
Hemoglobin 
Glucose 
Glucose 
Hematocrit 
Sodium 
Protein 
Red blood cell 
Potassium 
Specific gravity 
White blood cell (WBC) 
Calcium 
pH 
Platelets 
Chloride 
Ketones 
WBC Differential 
CO2 
Bilirubin 
Inorganic phosphate 
Urobilinogen 
Blood urea nitrogen 
Nitrite 
Creatinine 
Blood* 
Creatinine clearance (estimated) 
Leukocytesa 
Aspartate transaminase (AST) 
Alanine transaminase (ALT) 
Gamma-glutamyl transferase (GGT) 
Total bilirubin (TBL) (direct bilirubin reflex if elevated) 
Albumin 
Alkaline phosphatase (ALP) 
Uric acid 
a Microscopic examination will be performed if blood or leukocytes are detected by dipstick. 
For women of childbearing potential, a serum pregnancy test will be performed at Screening and 
Day 180/End of Study/Early Termination, and any Unscheduled Visits. Urine pregnancy tests 
will be performed at Day 1, Day 22, Day 43, and Day 90 (refer to section 5). Female subjects of 
childbearing potential must have a negative pregnancy test at the Screening Visit and at Day 1 
(Baseline), Day 22, and Day 43 to receive treatment in the study. If necessary, additional urine 
pregnancy tests can be performed at any time during the study at the discretion of the 
Investigator. Urine pregnancy test kits will be supplied by the Sponsor. 

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14.11. 
Physical Examination 
A complete physical examination will be performed at the Screening Visit. All examinations will 
be performed by a physician or health professional listed on the Form FDA 1572 and licensed to 
perform physical examinations. Height and body weight will be measured and recorded at 
screening. 
The Investigator will review all physical exam findings for clinical significance. Any physical 
exam finding meeting the Investigator’s or Sponsor’s criteria for clinical significance will be 
recorded as an AE or SAE as appropriate (see section 14.1.1, Adverse Events and section 14.1.2, 
Serious Adverse Events). 
At screening, the Investigator will also assess the subject’s skin type using the Fitzpatrick scale 
(Table 10). Only the Fitzpatrick Scale shown below may be used during the study. 
Table 10: 
Fitzpatrick Scale 
I 
Pale white skin, blue/hazel eyes, blond/red hair  
Always burns, does not tan  
II 
Fair skin, blue eyes  
Burns easily, tans poorly  
III 
Darker white skin  
Tans after initial burn  
IV 
Light brown skin  
Burns minimally, tans easily  
V 
Brown skin  
Rarely burns, tans darkly easily 
VI 
Dark brown or black skin 
Never burns, always tans darkly  
Follow-up body weight will be measured before injection on Day 22 and Day 43 and at the 
Day 90 and Day 180 visits. 
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 
To have a sufficient safety database of subjects establishing safety following exposure to 
EN3835, up to 150 subjects will be enrolled and monitored for 6 months in accordance with ICH 
guidance. 
17.2. 
Subject Populations 
The following populations are considered in the statistical analysis of the study: safety, 
effectiveness and per-protocol (PP). 
17.2.1. 
Safety Population 
The safety population is defined as all enrolled subjects who have at least one injection of study 
medication. All safety parameters will be summarized based on this population. 
17.2.2. 
Effectiveness Population 
The effectiveness population is defined as all subjects in Safety Population with a baseline and at 
least 1 post-injection evaluation of the Investigator CR-PCSS in at least one treatment area. All 
evaluations of effectiveness will be based on the effectiveness population. 
17.2.3. 
Per-Protocol (PP) Population 
Not applicable in the current study. 
17.3. 
Subject Disposition 
The number of subjects included in each study population will be summarized by assigned 
region (buttock or thigh) and overall. Subjects excluded from the safety and effectiveness 
populations will be listed. 
The number and percentage of subjects completed and prematurely discontinued during the 
treatment periods will be presented for each assigned region (buttock or thigh) and overall. 
Reasons for premature discontinuation from the treatment period as recorded on the termination 
page of the eCRF will be summarized (number and percentage) by assigned region and overall 
for all enrolled subjects. 
17.4. 
Demographics and Other Baseline Characteristics 
The summarization of demographic variables (eg, age, sex, race, weight, height, and BMI), 
medical and surgical history, and other baseline characteristics relevant to the indication studied 
in the study will be presented. 

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Demographic characteristics, including sex, age, age group, race, height, and weight, will be 
summarized by assigned region and overall, for Safety and Effectiveness Populations, using 
appropriate descriptive statistics. The descriptive summaries will include frequency tables for all 
categorical response variables and n, mean, standard deviation (SD), median, minimum and 
maximum for all continuous variables. 
17.5. 
Effectiveness Analyses  
17.5.1. 
Effectiveness Variables 
 Proportion at each level of improvement in the CR-PCSS of each assigned treatment 
area (Day 22, Day 43, Day 90, and Day 180): 
 Proportion of responders defined as subjects with an improvement in severity 
from baseline of at least 2 levels of severity in the CR-PCSS 
 Proportion of responders defined as subjects with an improvement in severity 
from baseline of at least 1 level of severity in the CR-PCSS 
 Proportion of responses at each level of the subject satisfaction with cellulite 
treatment (Day 180) 
All effectiveness variables will be summarized as the number and percentages. 
Mean and standard deviation for changes in CR-PCSS from baseline will be summarized. 
17.6. 
Safety Analyses 
Safety variables include adverse events, laboratory parameters, vital signs, ECG (screening 
only), and physical examination. For each safety parameter, the last assessment made prior to the 
first dose of study drug will be used as the baseline for all analyses of that safety parameter. 
17.6.1. 
Prior, Concomitant, and Follow-up Medication 
The World Health Organization (WHO) Drug Dictionary will be used to classify prior and 
concomitant medications by therapeutic class. Prior medication will be defined as any 
medication taken prior to the first dose of study drug. Concomitant medication is defined as any 
medication taken on or after the date of first dose of study drug. 
Prior and concomitant medication use will be summarized descriptively by the number and 
percentage of subjects for each preferred term (generic name from WHO dictionary) by 
treatment. Multiple use of the same medication by a subject will be counted only once. 
17.6.2. 
Study Drug Exposure 
The following information regarding treatment will be summarized per each treated area: 
 Total number of treatment visits 
 Number of subjects who had treatment visit done or treatment visit not done at each 
treatment day 

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 For subjects who had the treatment visit done, the number of subjects who got all 
12 injections per treatment area 
 Number of injections given at each treatment visit 
 Number of dimples treated at each treatment visit 
 Average number of injections per dimple at each treatment visit 
Subjects who did not receive all three treatment visits and who did not receive a total of 
24 injections at a treatment visit will be listed. 
17.6.3. 
Measurement of Treatment Compliance 
Not applicable (The study drug is administered at the site by the study Investigator). 
17.6.4. 
Adverse Events 
The Medical Dictionary for Regulatory Activities (MedDRA) will be used to code AEs. 
An AE (classified by preferred term) that started on or after the date of the first dose of the study 
drug will be considered a TEAE if it was not present prior to the first dose of study drug, or was 
present prior to the first dose of study drug but increased in intensity during the treatment period. 
If more than 1 AE is reported prior to the first dose of study drug and coded to the same 
preferred term, then the AE with the greatest intensity will be used as the benchmark for 
comparison to the AEs occurring during the treatment period which were also coded to that 
preferred term. Any AE present prior to the first dose of study drug that increases in intensity 
during the treatment period will be re-entered with a new start date of the date of increased 
intensity. 
Descriptive statistics (the number and percentage) for subjects reporting TEAEs 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. 
Listings will be presented for all subjects. Additionally, listings will be presented for subjects 
with SAEs, subjects with AEs leading to discontinuation of study or study drug, and subjects 
who die (if any). 
17.6.5. 
Vital Signs 
Descriptive statistics for vital signs (eg, systolic and diastolic blood pressure, pulse rate, and 
body weight) and their changes from baseline at each visit and at the end of study will be 
presented. Vital signs listings for all subjects will be provided. 
Vital sign values are potentially clinically important (PCI) if they meet both the observed value 
criteria and the change from baseline criteria. The criteria for PCI vital sign values will be 
detailed in the Statistical Analysis Plan (SAP). The PCI percentages will be calculated relative to 
the number of subjects with baseline and at least one post-baseline assessment. A supportive 

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listing of subjects values will be provided including the subject ID, study center, baseline and 
post-baseline values. 
17.6.6. 
Clinical Laboratory Parameters 
Descriptive statistics for clinical laboratory values in International System of Units (SI units) and 
changes from baseline at Day 180 will be presented for each clinical laboratory parameter. 
Listings for clinical laboratory values for all subjects will be provided. 
The number and percentage of subjects with potentially clinically important (PCI) post-baseline 
clinical laboratory values will be tabulated. The criteria for PCI laboratory values will be detailed 
in the Statistical Analysis Plan (SAP). The PCI percentages will be calculated relative to the 
number of subjects with at least one post-baseline assessment. A supportive listing of subjects 
with post-baseline PCI values will be provided, including the subject ID, study center, baseline 
and post-baseline values. 
17.6.7. 
Electrocardiogram 
Not applicable (ECG is done only at screening for the subject’s enrollment eligibility). 
17.6.8. 
Physical Examination 
Body weight and BMI at Day 22, Day 43, Day 90, and Day 180 as well as their change from 
baseline (Day 1) at those time points will be presented.  
17.6.9. 
Other Safety Measurements 
Not applicable. 
17.7. 
Pharmacokinetic Analyses 
Not applicable. 
17.8. 
Pharmacodynamic Analyses 
Not applicable. 
17.9. 
Other Data (eg, Health Economics/QOL, Pharmacogenetic, etc.) 
Not applicable. 
17.10. 
Interim Analysis 
No interim analysis is planned for this study. 
17.11. 
Statistical Software 
Statistical analyses will be performed using Version 9.3 (or higher) of SAS® (SAS Institute, 
Cary, NC). 

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

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

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

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

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24. 
INVESTIGATOR OBLIGATIONS 
24.1. 
Regulatory Documents 
The Investigator is responsible for creating and/or maintaining all study documentation required 
by 21CFR 50, 54, 56, and 312, ICH, E6 section 8, as well as any other documentation defined in 
the protocol or the Investigator Agreement. The Investigator must maintain the documentation 
relating to this study and permit Endo Pharmaceuticals Inc. or a member of a regulatory agency 
access to such records. 
The Investigator must provide the following key documents to Endo Pharmaceuticals Inc. prior 
to the start of the study: 
 A completed and signed Form FDA1572. If during the course of the study any 
information reported on the Form FDA 1572 changes, a revised Form FDA1572 must 
be completed and returned to Endo Pharmaceuticals Inc. for submission to the FDA. 
For studies executed outside the United States, documentation required by the 
governing regulatory authority may be substituted for the Form FDA 1572. 
 A fully executed contract 
 The Investigator’s Statement page in this protocol signed and dated by the 
Investigator and any subsequent amendment signature pages 
 The IB acknowledgment of receipt page 
 Curricula vitae for the Principal Investigator and all Sub-Investigators listed on Form 
FDA 1572, including a copy of each physician’s license (if applicable) 
 A copy of the original IRB/IEC approval for conducting the study. If the study is 
ongoing, renewals must be submitted at yearly intervals or shorter intervals defined 
by the IRB/IEC. All subsequent modifications must be submitted and approved by the 
IRB, as described in section 21.1 
 A copy of the IRB/IEC-approved informed consent form 
 A list of IRB/IEC members or DHHS Assurance Number 
 Laboratory certifications and normal ranges (if local labs are required by the protocol) 
 A financial disclosure agreement completed and signed by the Investigator and all 
Sub-Investigators listed on Form FDA 1572. Investigator site staff that submitted an 
initial financial disclosure are also responsible for informing Endo Pharmaceuticals 
Inc. of any changes to their initial financial disclosure form 1 year after the 
completion of the study. 
A complete list of required regulatory documents will be supplied by Endo Pharmaceuticals Inc. 
or its representative. 

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24.2. 
Delegation of Responsibilities and Adequate Resources 
The Investigator should have adequate time to conduct the study properly and should have an 
adequate number of qualified staff to assist with the conduct of the study. The Investigator shall 
delegate tasks only to individuals qualified by education, training and experience to perform the 
delegated tasks. The Investigator shall have direct oversight of all delegated activities and shall 
document delegation of responsibilities. The Investigator is responsible for ensuring all delegated 
staff have been properly trained on the protocol and their assigned study responsibilities. 
24.3. 
Medical Care of Study Subjects 
The Investigator and/or a qualified Sub-Investigator shall be responsible for the subjects’ 
medical care. Any unrelated medical condition discovered during the course of the study should 
be communicated to the subject so that they may seek appropriate medical care. The Investigator 
will report all AEs as required by the protocol (section 14.5). The Investigator will inform study 
subjects of new information regarding the study drug as it becomes available. 
24.4. 
Use of Investigational Materials 
The Investigator will acknowledge that the study drug supplies are investigational and as such 
must be used strictly in accordance with the protocol and only under the supervision of the 
Principal Investigator or Sub-Investigators listed on Form FDA1572 (or other regulatory 
document, depending on region). Study drug must be stored in a safe and secure location. At 
study initiation, a representative from Endo Pharmaceuticals Inc. will inventory the study drug at 
the site. The Investigator must maintain adequate records documenting the receipt and 
disposition of all study supplies. Endo Pharmaceuticals Inc. or its representative will supply 
forms to document total inventory as well as subject specific accountability. The Investigator is 
responsible for monitoring subject’s use of the study drug to ensure compliance with the 
protocol. All study supplies shall be returned to Endo Pharmaceuticals Inc. or its designee. 
24.5. 
Retention of Records 
Federal and local regulations require that the Investigator retain a copy of all regulatory 
documents and records that support the data for this study (eg, informed consents, laboratory 
reports, source documents, study drug dispensing records) for whichever of the following is the 
longest period of time: 
 A period of 2 years following the final date of approval by the FDA or other 
regulatory agency of the study drug for the purposes that were the subject of the 
investigation; or 
 A period of 5 years following the date on which the results of the investigation were 
submitted to the FDA or other regulatory agency in support of, or as part of, an 
application for a research or marketing permit for the study drug for the purposes that 
were the subject of the investigation 
Endo Pharmaceuticals Inc. will notify Investigators once one of the above 2 timeframes has been 
satisfied. 

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If the investigation does not result in the submission of the data in support of, or as part of, an 
application for a research or marketing permit, records must be retained for a period of 2 years 
following notification by Endo Pharmaceuticals Inc. that the entire clinical investigation (not 
merely the Investigator’s portion) is completed, terminated, or discontinued or 2 years following 
withdrawal of the Investigational New Drug application (IND)/Clinical Trial Authorization 
(CTA) or request for marketing approval (New Drug 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 celllulite using a 1440-nm pulsed laser with one-year 
follow-up. Aesthet Surg J. 2011;31(3):328-41. 
11. Investigational Brochure: Collagenase Clostridium Histolyticum for Injection 
(AA4500/EN3835), Version 7.0. Endo Pharmaceuticals Inc.; May 2016. 
12. Hexsel DM, Dal’Forno T, Hexsel CL. A validated photonumeric cellulite severity scale. 
J Eur Acad Dermatol Venereol. 2009;23(5):523-8. 
13. Nürnberger F, Müller G. So-called cellulite: an invented disease. J Dermatol Surg Oncol. 
1978;4(3):221-9. 
 

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

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

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

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

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

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