Clinical trial NCT04677712
Conditions: Edematous Fibrosclerotic Panniculopathy (EFP) Cellulite
Keywords: Bruising mitigation CCH-aaes
Sponsor: Endo Pharmaceuticals
Start date: 2020-12-28; Completion date: 2021-09-02
Enrollment: 48 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will investigate treatments that may mitigate bruising after QWO™ (Collagenase clostridium histolyticum \[CCH\]-aaes) treatment of cellulite in the buttocks.

Detailed description:
CCH-aaes is indicated for the treatment of moderate to severe cellulite in the buttocks of adult women. Since bruising may be bothersome, this study will investigate treatments that may mitigate bruising after treatment of cellulite in the buttocks.

Arms: arm 1: CCH-aaes was administered without mitigation treatment (control group). arm 2: CCH-aaes was administered with compression garment. arm 3: CCH-aaes was administered with instant cold packs. arm 4: CCH-aaes was administered with arnica gel patches (OcuMend). arm 5: CCH-aaes was administered with INhance Post-Injection Serum with TriHex Technology® arm 6: CCH-aaes was administered with PDL.
Interventions: intervention 1: CCH-aaes intervention 2: Compression intervention 3: Cold Packs intervention 4: Arnica Gel intervention 5: INhance® intervention 6: PDL
Intervention descriptions: intervention 1: Participants were administered CCH-aaes by subcutaneous injection to both buttocks. intervention 2: Participants used a compression garment on both buttocks following subcutaneous CCH-aaes injections. intervention 3: Participants used cold packs applied to the right buttock for 5-10 minutes immediately after subcutaneous CCH-aaes injections. intervention 4: Participants used Arnica Gel Patches (Arnica montana 50% and Ledum palustre) immediately after the CCH-aaes injection to the right buttock. intervention 5: Participants used INhance Post-injection Serum topically immediately after the CCH-aaes injection to the right buttock. intervention 6: Investigators applied one treatment with PDL to the right buttock between days 1-7 after injection.

Protocol documents:
Prot_000.pdf: 
Protocol 
1.
TITLE PAGE
Endo Pharmaceuticals Inc. 
1400 Atwater Drive 
Malvern, PA 19355 USA 
EN3835-401 
MOBI: A PHASE 4, OPEN-LABEL STUDY TO ASSESS EFFECTS OF 
MITIGATION TREATMENTS ON BRUISING OF CCH-AAES 
TREATMENT OF BUTTOCK CELLULITE IN ADULT FEMALES  
Sponsor Name: Endo Pharmaceuticals Inc. 
Sponsor Legal Registered Address: 1400 Atwater Drive, Malvern, PA 19355 
Regulatory Agency Identifier Number: Investigational New Drug Application (IND) 110077 
Original Protocol: 20 May 2022 
 
 
 
 
 
 
 
 
NCT #NCT04677712


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TABLE OF CONTENTS 
1. 
TITLE PAGE ................................................................................................................1 
1. 
PROTOCOL SUMMARY ............................................................................................6 
1.1. 
Synopsis ........................................................................................................................6 
1.2. 
Study Schema .............................................................................................................10 
1.3. 
Schedule of Assessments ............................................................................................11 
2. 
INTRODUCTION ......................................................................................................14 
2.1. 
Background .................................................................................................................14 
2.2. 
Rationale .....................................................................................................................14 
2.3. 
Benefit-Risk Assessment ............................................................................................14 
2.3.1. 
Compression Garments ...............................................................................................15 
2.3.2. 
Instant Cold Packs ......................................................................................................15 
2.3.3. 
Arnica (OcuMend) Patches .........................................................................................15 
2.3.4. 
INhance Post-Injection Serum with TriHex Technology® .........................................17 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................18 
3.1. 
Objectives and Endpoints ...........................................................................................18 
4. 
STUDY DESIGN .......................................................................................................20 
4.1. 
Overall Design ............................................................................................................20 
4.2. 
Scientific Rationale for the Study Design ..................................................................21 
4.2.1. 
Changes to the Study Design Due to COVID-19 .......................................................22 
4.3. 
Justification for Endpoints ..........................................................................................22 
4.4. 
Justification for Dose ..................................................................................................22 
4.5. 
End of Study Definition ..............................................................................................22 
5. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................23 
5.1. 
Subject Inclusion Criteria ...........................................................................................23 
5.2. 
Subject Exclusion Criteria ..........................................................................................23 
5.3. 
Lifestyle Considerations .............................................................................................25 
5.4. 
Screen Failures ............................................................................................................25 
6. 
STUDY TREATMENT ..............................................................................................26 
6.1. 
Selection and Marking of Dimples .............................................................................26 
6.2. 
Treatment Administration ...........................................................................................26 
6.2.1. 
QWO (CCH-Aaes) ......................................................................................................26 
6.2.2. 
Mitigation Treatments ................................................................................................26 


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6.2.3. 
QWO (CCH-Aaes) Preparation/Handling/Storage .....................................................27 
6.3. 
Measures to Minimize Bias ........................................................................................28 
6.3.1. 
Mitigation Treatment Assignment Table ....................................................................28 
6.4. 
Study Treatment Compliance .....................................................................................28 
6.5. 
Prior and Concomitant Medications and Procedures ..................................................28 
6.5.1. 
Prohibited Medications ...............................................................................................28 
6.5.2. 
Suggested Concomitant Medications and Procedures ................................................29 
6.5.3. 
COVID-19 Related Protocol Deviations ....................................................................29 
7. 
DISCONTINUATION FROM STUDY TREATMENT AND STUDY 
WITHDRAWAL ........................................................................................................30 
7.1. 
Discontinuation of Study Treatment ...........................................................................30 
7.2. 
Subject Withdrawal from the Study ...........................................................................30 
7.3. 
Lost to Follow-up .......................................................................................................31 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................32 
8.1. 
Screening Assessments ...............................................................................................32 
8.1.1. 
Medical History ..........................................................................................................32 
8.1.2. 
Physical Examination .................................................................................................32 
8.1.1. 
Vital Signs ..................................................................................................................32 
8.1.2. 
Fitzpatrick Skin Scale .................................................................................................33 
8.1.3. 
Hexsel Cellulite Scale Severity ..................................................................................33 
8.1.4. 
Clinician Reported Photonumeric Cellulite Severity Scale ........................................33 
8.2. 
Efficacy Assessments .................................................................................................33 
8.2.1. 
Digital Photography ....................................................................................................34 
8.2.2. 
Investigator Assessment of Bruising Severity Scale ..................................................34 
8.2.3. 
Investigator-Bruising Improvement Scale ..................................................................34 
8.2.4. 
Investigator-Global Aesthetic Improvement Scale .....................................................35 
8.2.5. 
 
8.2.6. 
Subject-Bruising Improvement Scale .........................................................................35 
8.2.7. 
Patient Bother by Bruising Scale ................................................................................36 
8.3. 
Safety Assessments .....................................................................................................36 
8.4. 
Adverse Events and Serious Adverse Events .............................................................36 
8.4.1. 
Time Period and Frequency for Collecting Adverse Event and Serious 
Adverse Event Information .........................................................................................37 


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8.4.2. 
Method of Detecting Adverse Events and Serious Adverse Events ...........................37 
8.4.3. 
Follow-up of Adverse Events and Serious Adverse Events .......................................37 
8.4.4. 
Regulatory Reporting Requirements for Serious Adverse Events .............................37 
8.4.5. 
Pregnancy ...................................................................................................................38 
8.4.6. 
Adverse Events/Serious Adverse Events Experienced by Nonsubjects 
Exposed to Study Treatment .......................................................................................38 
8.5. 
Treatment Overdose ....................................................................................................39 
8.5.1. 
Treatment Abuse/Misuse ............................................................................................39 
9. 
STATISTICAL CONSIDERATIONS AND METHODS .........................................40 
9.1. 
Sample Size Determination ........................................................................................40 
9.2. 
Populations for Analysis .............................................................................................40 
9.3. 
Statistical Hypotheses and Analyses ..........................................................................40 
9.3.1. 
Efficacy Analysis ........................................................................................................40 
9.3.2. 
Safety Analyses ..........................................................................................................40 
9.3.2.1. 
Adverse Events ...........................................................................................................40 
9.4. 
Interim Analysis ..........................................................................................................41 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................42 
10.1. 
Appendix 1: Regulatory, Ethical and Study Oversight Considerations .....................42 
10.1.1. 
Regulatory and Ethical Considerations ......................................................................42 
10.1.2. 
Financial Disclosure ...................................................................................................42 
10.1.3. 
Informed Consent Process ..........................................................................................43 
10.1.4. 
Data Protection ...........................................................................................................43 
10.1.5. 
Dissemination of Clinical Study Data ........................................................................44 
10.1.6. 
Data Quality Assurance ..............................................................................................44 
10.1.7. 
Source Documents ......................................................................................................44 
10.1.8. 
Study and Site Closure................................................................................................45 
10.1.9. 
Publication Policy .......................................................................................................45 
10.2. 
Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up and Reporting .........................................................................46 
10.2.1. 
Definitions ..................................................................................................................46 
10.2.2. 
Relationship to Study Treatment ................................................................................47 
10.2.3. 
Intensity Assessment ..................................................................................................47 


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10.2.4. 
Reporting Adverse Events and Serious Adverse Events ............................................47 
10.2.4.1. 
Reporting Adverse Events ..........................................................................................47 
10.2.4.2. 
Reporting Serious Adverse Events .............................................................................48 
10.2.4.3. 
Follow-up Procedures for Serious Adverse Events ....................................................48 
10.3. 
Appendix 3: Contraceptive Guidance and Collection of Pregnancy 
Information .................................................................................................................48 
10.4. 
Abbreviations ..............................................................................................................48 
11. 
INVESTIGATOR’S STATEMENT ...........................................................................50 
12. 
REFERENCES ...........................................................................................................51 
 
LIST OF TABLES 
Table 1: 
Distribution of Mitigation Treatments ........................................................................20 
Table 2: 
Investigator-Global Aesthetic Improvement Scale .....................................................35 
 
 


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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Marketed Product: QWOTM(CCH-aaes) 
Name of Active Ingredient: Collagenase clostridium histolyticum (CCH) 
Title of Study: MOBI: A Phase 4, Open-Label Study to Assess Effects of Mitigation 
Treatments on Bruising of CCH-Aaes Treatment of Buttock Cellulite in Adult Females 
Lead Principal Investigator: Not applicable 
Phase of development: 4 
Objectives and Endpoints: 
Primary Objective 
Primary Endpoint 
To assess the effect of mitigation 
treatments on bruising in the 
buttocks of subjects with cellulite 
after the first treatment of QWO 
(CCH-aaes).  
• 
The proportion of subjects by buttock at each level of 
bruising on the Investigator Assessment of Bruising 
Severity Scale, at Day 4, 3 days after QWO (CCH-aaes) 
injection. This 5-level scale ranges from 0 to 4, with 0 
indicating no bruising or almost none, and 4 indicating 
very severe bruising.  
Secondary Objectives 
Secondary Endpoints 
To assess investigator assessment 
of bruising with mitigation 
treatments in subjects with cellulite 
after the first treatment of QWO 
(CCH-aaes) .  
• 
The proportion of subjects for whom the investigator 
reported an improvement of bruising on the mitigation 
treated buttock on Days 4 and 7 as measured on the 
Investigator-Bruising Improvement Scale (I-BIS), a 
3-point Likert scale, with a score on the higher end of the 
range indicating improvement with treatment.    
• 
The proportion of subjects by buttock with bruising at 
each level of the Investigator Assessment of Bruising 
Severity Scale, by visit. This 5-level scale ranges from 0 
to 4, with 0 indicating no bruising or almost none, and 4 
indicating very severe bruising. 
To assess subject assessment of 
bruising with mitigation treatments 
in subjects with cellulite after the 
first treatment of QWO (CCH-
aaes). 
• 
The proportion of subjects treated with QWO (CCH-aaes) 
reporting an improvement of bruising on the mitigation 
treated buttock on Days 4 and 7 as measured on the 
Subject-Bruising Improvement Scale (S-BIS), a 3-point 
Likert scale, with a score on the higher end of the range 
indicating improvement of bruising with treatment.  
• 
The proportion of subjects by buttock bothered by the 
appearance of bruising on each buttocks on the Patient 
Bother by Bruising Scale, a 4-point scale, with a score of 
1 indicating not bothered at all, and a score of 4, 
indicating, extremely bothered. 
 


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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Marketed Product: QWOTM(CCH-aaes) 
Name of Active Ingredient: Collagenase clostridium histolyticum (CCH) 
 
Secondary Objectives 
Secondary Endpoints 
To assess the level of aesthetic 
improvement of cellulite after 
treatment of QWO (CCH-aaes) 
with and/or without bruising 
mitigation treatment. 
• 
The proportion of subjects with an improved (+1 or 
better) score on the Investigator-Global Aesthetic 
Improvement Scale (I-GAIS) for either buttock at the Day 
71 Visit compared to Baseline. The I-GAIS is a 7-level 
scale ranging from +3 (very much improved) to -3 (very 
much worse). 
To assess the safety of QWO 
(CCH-aaes) with mitigation 
treatment in subjects with cellulite. 
• 
Percentage of subjects reporting each adverse event (AE) 
and treatment emergent adverse event (TEAEs). 
Exploratory Objective 
Exploratory Endpoint 
 
 
 
 
 
 
  
• 
 
 
 
 
 
 
Overall Design: 
This is a Phase 4, multicenter, open-label, multiple dose study to assess the effect of mitigation 
treatments on injection site bruising and safety in adult women with moderate cellulite in the 
buttocks treated with QWO (CCH-aaes). Approximately 75 subjects will be screened in order 
to enroll approximately 48 subjects in 6 cohorts. 
At the Screening Visit, subjects who meet all inclusion criteria and have no exclusion criteria 
according to the investigator’s assessment will be assigned to 1 of 6 treatment cohorts. 
Subjects will be allocated to cohorts using a site specific Mitigation Treatment Assignment 
Table provided by the sponsor. 
Pending site capabilities and available mitigation treatments, each site will administer each 
mitigation treatment, with approximately 1-3 subjects assigned to each mitigation treatment as 
shown in Table 1. Mitigation treatments will be administered at or after the initial treatment 
session of QWO (CCH-aaes). 


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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Marketed Product: QWOTM(CCH-aaes) 
Name of Active Ingredient: Collagenase clostridium histolyticum (CCH) 
Table 1: 
Distribution of Mitigation Treatments 
 
 
QWO (CCH-aaes) a 
Mitigation Treatment 
 
N Left Buttock 
Right Buttock 
Left Buttock 
Right Buttock 
Cohort 1 
8 
Up to 0.84 mg 
Up to 0.84 mg 
None 
Cohort 2 
8 
Up to 0.84 mg 
Up to 0.84 mg 
Compression garment 
Cohort 3 
8 
Up to 0.84 mg 
Up to 0.84 mg 
None 
Instant cold packs  
Cohort 4 
8 
Up to 0.84 mg 
Up to 0.84 mg 
None 
Arnica patches 
Cohort 5 
8 
Up to 0.84 mg 
Up to 0.84 mg 
None 
INhance Post-Injection 
Serum with TriHex 
Technology 
Cohort 6 
8 
Up to 0.84 mg 
Up to 0.84 mg 
None 
PDL treatment b 
a. 
For each subject, an identical dose and injection count of QWO (CCH-aaes) should be administered for the 
first treatment session to each buttock. The number of injections may differ among subjects. 
b. 
Pulse dye laser (PDL) may be used at the settings selected according to the investigator’s discretion. 
 
Eligible subjects will receive up to 0.84 mg of QWO (CCH-aaes) per buttock in both buttocks 
for a total dose of 1.68 mg per treatment session for 3 treatment sessions (Day 1, Day 21 
±3 days, and Day 43 ±3 days). To reduce variance in the bruising observed on the left and 
right buttocks after the first treatment session of QWO (CCH-aaes), each buttock should be 
treated with the same number of QWO (CCH-aaes) injections on Day 1, of up to 12 injections 
per buttock. The number of injections may differ between treatment sessions; 12 injections per 
buttock may be administered during the first treatment session followed by fewer injections 
per buttock during the second and third treatment sessions. 
Subjects will return to the site approximately on Days 2, 4, 7, and 14 (ie, 1, 3, 6, and 13 days 
after injection on Day 1) for additional evaluations and digital photography obtained with 
standardized parameters. After the first mitigation treatment session, on Days 4 and 7, the 
effect of mitigation treatments on the severity of bruising will be assessed using the I-BIS and 
the Investigator Assessment of Bruising Severity Scale. The effect of mitigation treatments on 
the severity of bruising will be assessed by subjects on the S-BIS and the Patient Bother by 
Bruising Scale. Safety will be assessed throughout the study by collecting AEs, and TEAEs, 
and assessing injection site reactions in the buttocks. 
 
  
At the investigator’s discretion, for the second and third QWO (CCH-aaes) treatment sessions 
on Days 22 and 43, subjects will be permitted to receive the same mitigation treatment to the 
right buttock as received during the first QWO (CCH-aaes) treatment session. The severity of 
bruising will be assessed at each visit. Subject and investigator assessments of satisfaction, 
aesthetic improvement, and digital photography will also be conducted on Days 22 (± 3 days) 
and 43 (±3 days). Subjects will return to the site for last study visit on Day 71 for additional 
investigator assessments of bruising and digital photography. 
Disclosure Statement: This is an interventional open-label, post-marketing study to evaluate 
the effect of mitigation treatments on the bruising induced by QWO (CCH-aaes). The efficacy 
of the mitigation treatments in reducing bruising and the safety of QWO (CCH-aaes) with 
mitigation treatments will also be assessed. 


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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Marketed Product: QWOTM(CCH-aaes) 
Name of Active Ingredient: Collagenase clostridium histolyticum (CCH) 
Number of Subjects (planned): A maximum of 75 adult female subjects will be screened in 
order to enroll 48 adult female subjects into 6 cohorts, such that approximately 45 evaluable 
subjects complete the study. 
Treatment Groups and Duration:  
It is intended to enroll 6 treatment cohorts of 8 subjects each. Cohort 1, will receive 
QWO (CCH-aaes) and no mitigation treatment. Cohorts 2-6 will receive QWO (CCH-
aaes) with different mitigation treatments. 
Subjects will complete the study on Day 71. The expected duration of subject participation is 
up to 92 days. 
Data Monitoring Committee: No data monitoring committee will be used for this study. 
 


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1.2.
Study Schema
BID = twice daily, ET= early termination, rt =right, QID = 4 times daily 


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1.3. 
Schedule of Assessments 
 
Screening Period 
Treatment Period 
Follow-up Period 
Procedures 
Day -14 
Day 1 
(Baseline) 
Day 
2 
Day 
4 
Day 
7 
Day 
14 
Day 
22 
(±3d) 
Day 
43 
(±3d) 
Day 71//ET 
(+ 7d) 
Informed consent 
X 
 
 
 
 
 
 
 
 
Inclusion/Exclusion criteria 
X 
 
 
 
 
 
 
 
 
Medical history/surgical 
history/cellulite history including 
previous treatments 
X 
 
 
 
 
 
 
 
 
Prior/Concomitant 
medications/procedures (including all 
prior medications/procedures for 
cellulite) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination (including 
height) 
X 
 
 
 
 
 
 
 
 
Weight 
X 
 
 
 
 
 
 
 
X 
Fitzpatrick skin type 
Xa 
 
 
 
 
 
 
 
 
Vital signs 
X 
Xb 
 
 
 
 
 
 
 
Digital photographyc 
 
X 
X 
X 
X 
X 
Xd 
Xd 
X 
Cohort assignment 
Xe 
 
 
 
 
 
 
 
 
QWO (CCH-aaes) administration 
 
X 
 
 
 
 
X 
X 
 
Subject Assessments 
  
 
 
 
 
 
 
 
 
 
Subject-Bruising Improvement Scale 
(S-BIS) 
 
 
X 
X 
X 
X 
Xd 
 
 
Patient Bother by Bruising Scaleg 
 
 
 
X 
X 
 
Xd 
 
 
Investigator Assessments 
Hexsel Cellulite Severity Scale (CSS) 
Subsection D 
Xh 
 
 
 
 
 
 
 
 
Clinician Reported Photonumeric 
Cellulite Severity Scale (CR-PCSS)  
Xi 
 
 
 
 
 
 
 
 
Selection and marking of dimples to 
be treated within both buttocks 
 
Xc 
 
 
 
 
Xd 
Xd 
 
Investigator Assessment of Bruising 
Severity Scale 
  
X 
X 
X 
X 
X 
Xd 
 
 
Investigator- Bruising Improvement 
Scale (I-BIS)j 
 
 
X 
X 
X 
X 
Xd 
 
 


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Screening Period 
Treatment Period 
Follow-up Period 
Procedures 
Day -14 
Day 1 
(Baseline) 
Day 
2 
Day 
4 
Day 
7 
Day 
14 
Day 
22 
(±3d) 
Day 
43 
(±3d) 
Day 71//ET 
(+ 7d) 
Investigator- Global Aesthetic 
Improvement Scale (I-GAIS)  
 
 
 
 
 
 
Xd 
X 
X 
 
 
Screening Period 
Treatment Period 
Follow-up Period 
Procedures 
Day -14 
Day 1 
(Baseline) 
Day 
2 
Day 
4 
Day 
7 
Day 
14 
Day 
22 
(±3d) 
Day 
43 
(±3d) 
Day 71//ET 
(+ 7d) 
Mitigation Treatment Cohorts 
Compression garments  
 
Xk,p 
 
 
 
 
Instant cold packs to the right buttock 
only 
 
Xl,p 
 
 
 
 
 
 
 
Arnica patches (OcuMend®) to the 
right buttock only 
 
Xm, p 
 
 
 
 
 
 
INhance Post-Injection Serum with 
TriHex Technology® to the right 
buttock only 
 
Xn,p 
 
 
 
 
Pulse dye laser (PDL) treatment to 
the right buttock only 
 
Xo,p 
 
 
 
 
Injection site reactions/local 
tolerability in each buttock treated 
 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse events (AEs) 
 
Xq 
a  Subjects with a Fitzpatrick skin rating of I-III will be included. 
b  Before injection and approximately 30 minutes after injection. Pulse and blood pressure should be collected after the subject has been sitting for 5 minutes.  
c  Buttocks will be photographed before and after injection site and dimple marking on Days 1, 22, and 43. Buttocks will also be photographed during the Days 2, 4, 
7, 14, and 71 visits (ET) (no dimple or injection site markings). 
d.  Before injection. 
e  Subjects will be assigned to 1 of 6 cohorts according to a site specific Mitigation Treatment Assignment Table. Cohort 1 =no mitigation treatment;  
Cohorts 2-6 = mitigation treatments 
f.  Before QWO (CCH-aaes) injection, and 5 and 15 minutes after injection. 
g  Using mirrors, or photographs captured either by the subject or another person with the subject’s imaging device (ie, cell phone, digital camera), or images 
captured by the investigator or designee using the site’s digital photography system. 
h  Baseline Hexsel CSS Subsection D must be ‘0’ (absence of flaccidity or sagging skin) or ‘1’ (slightly draped appearance) on each buttock. 
i   Baseline CR-PCSS rating must be a ‘3’ (moderate) on each buttock. 
j  Based on live assessments while the subject is in front of the investigator. 
k  Compression garments will be worn after QWO (CCH-aaes) injection on Day 1 and worn 24 hours a day for the next 7 days.  
l  Apply instant cold packs immediately after QWO (CCH-aaes) injection for 5-10 minutes immediately after CCH-aaes injection while subject is in a prone position. 


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m  Arnica patches applied BID for 2 days immediately after QWO (CCH-aaes) injection on Day 1. 
n   Inhance Post-Injection Serum is applied  QID directly on and around the injections site for up to 7 days after QWO (CCH-aaes) injection on Day 1, until 
resolution of bruising. 
o  PDL treatment between Days 1 (same day of QWO [CCH-aaes) injection) and Day 7 after QWO (CCH-aaes) treatment. PDL settings are according to the 
investigator’s discretion. 
p  For the second and third QWO (CCH-aaes) treatment sessions, at the investigator’s discretion, subjects will be allowed to use the same mitigation treatment in 
the same buttock (as applicable) that received mitigation treatment for the first CCH-aaes treatment session. 
q.  AEs will be collected from the time the subject signed the ICF until end of the study or early termination. 
BID = twice daily, d = Days, ET = early termination, ICF = informed consent form, QID = Four times daily 
 
 


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2. 
INTRODUCTION 
Collagenase clostridium histolyticum (CCH)-aaes (CCH, EN3835, CCH-aaes, QWO™) is a 
combination of bacterial collagenases AUX-I and AUX-II, in an approximate 1:1 mass ratio, 
Collagenase I (Clostridial class I collagenase [AUX-I]) and Collagenase II (Clostridial class II 
collagenase [AUX-II]). QWO (CCH-aaes) is FDA approved for the treatment of moderate to 
severe cellulite in the buttocks of adult women. 
2.1. 
Background 
The results of the pivotal studies (Studies EN3835-302 and -303) of QWO (CCH-aaes) in 
edematous fibrosclerotic panniculopathy, otherwise known as cellulite, supported FDA approval 
of QWO (CCH-aaes) for the treatment of moderate to severe cellulite in the buttocks of adult 
women. The approved dose of QWO (CCH-aaes) is 0.84 mg per treatment area (buttock) per 
treatment area for up to 2 treatment areas per treatment session, administered at 3 treatment 
sessions, approximately 21 days apart. This dose was shown to be an effective treatment of 
cellulite based on improvement in the severity of cellulite as determined by the investigator and 
the subject. Overall, the safety profile indicated that QWO (CCH-aaes) was well-tolerated (QWO 
Prescribing Information). Bruising (injection site bruising) was the most common AE (84%) in 
the Phase 3 studies. Bruising after the first treatment session was the most robust of the 3 
treatment sessions, with the incidence, duration and severity of bruising decreasing with each 
subsequent treatment session (Endo Clinical Study Reports EN3835-202, EN3835-205, 
EN3835-302, EN3835-303).  
2.2. 
Rationale 
Although QWO (CCH-aaes)-related post-injection bruising generally resolves within 21 days, 
and before the next treatment session, bruising is bothersome to subjects due to skin 
discoloration, and associated swelling and pain. This study will investigate treatments that may 
mitigate bruising after QWO (CCH-aaes) treatment of cellulite in the buttocks. 
Mitigation treatments that may potentially reduce bruising after QWO (CCH-aaes) injection 
were selected collaboratively with aesthetic physicians based on their experience using 
mitigation treatments when administering other injectable drugs during aesthetic procedures.  
A description of the chemistry, pharmacology, efficacy, and safety of QWO (CCH-aaes) is 
provided in the QWO Prescribing Information. 
2.3. 
Benefit-Risk Assessment 
QWO is approved for the treatment of moderate to severe cellulite in the buttocks of adult 
women.  
The selection of the mitigation treatments and their dose/regimen was a consensus based on the 
collaborative knowledge and experience of the investigators and Endo, the postulated mechanism 
of bruising of QWO (CCH-aaes) known to date, and/or supportive literature. 
The benefit and risk of each mitigation treatment is described in this section. 


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2.3.1. 
Compression Garments 
Post-operative compression garments can reduce post-operative bruising, edema, and discomfort 
(Gladfelter, 2007). Bruising is minimized by compression of small blood vessels and capillaries. 
Ill-fitting compression garments may cause pain. 
2.3.2. 
Instant Cold Packs 
Applying cold (cryotherapy) is commonly used treatment for soft tissue injury (Mayo et al, 
2013) and after aesthetic procedures (Brennan, 2014; Verner et al, 2019). Cold induces 
vasoconstriction and minimizes local cellular damage by restricting hemorrhage (Mayo et al, 
2013). It also reduces metabolic demand at the site of injury which aids in healing and recovery.  
Mayo et al (2013) compared the effect of bruise reduction treatments of either cold compresses, 
hydrogen peroxide 3%, an over the counter serum containing vitamin E oil, evening primrose oil, 
glycerin, and pulse dyle laser (PDL) in 17 patients. There was no significant difference among 
cold compresses, hydrogen peroxide, and over-the-counter serum in reducing time to bruise 
resolution.  
In a meta-analysis conducted by Lee et al (2017), there was a statistically significant reduction in 
a cold compress group vs a control group in eyelid ecchymosis after rhinoplasty, at 1 hour and 1 
day post-operatively. 
Nestor et al (2010) evaluated the use of a cooling device in subjects injected with hyaluronic acid 
dermal fillers. The use of a cooling system was associated with a mean ecchymosis reduction of 
88%, 89%, 80%, and 66% compared to control immediately after injection, at 1 hour, 3 hours, 
and the day after injection, respectively. 
Prolonged application of cold at very low temperatures should be avoided, since this may cause 
frostbite and nerve injuries (Swenson et al, 1996). 
2.3.3. 
Arnica (OcuMend) Patches  
Arnica montana is a perennial of the family Asteraceae. The flowers of its various species 
contain glycosides, terpinoids, amines, coumarins, and volatile oils (Knackstedt and 
Gatherwright, 2020). It is purported to have anti-inflammatory and tissue healing actions after 
trauma bruises or tissue injuries (Ianitti et al, 2016; Widegrow et al, 2020). Various homeopathic 
oral and topical preparations of different dosages are available. A recent literature review 
evaluated the efficacy of perioperative arnica in reducing edema, ecchymosis and pain after a 
variety of aesthetic surgeries including rhinoplasty, blepharoplasty, facial cosmetic surgeries, and 
laser procedures (Knacksted and Gatherwright, 2020). The data on arnica's effect post-laser 
treatments was equivocal, however there were differences in technique and application. 
Three randomized controlled studies of perioperative oral or topical arnica in rhinoplasty 
demonstrated decreased ecchymosis (Chaiet and Marcus, 2016; Totonchi and Guyuron, 2007; 
Simsek et al, 2016). In 2 randomized controlled studies of arnica in upper blepharoplasty, there 
was no difference in the use of oral (500 mg homeopathic dilution 3 times daily) (Kotlus et al, 
2010) or topical arnica (10%) applied twice daily (BID) (van Exsel et al, 2016), compared to 
placebo.  
There were 2 randomized controlled studies that evaluated topical arnica in patients undergoing 
either 585- or 595-nm laser treatment (Leu et al, 2010; Alonso et al, 2002). In the study 


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conducted by Leu et al (2010), moderate to severe bruises were induced using a 595-nm variable 
long-pulsed PDL (spot size 7 mm; fluence 9–11 J; pulse duration 1.5 ms; cooling with 30 ms 
spray, 20 ms delay with dynamic cooling device). Treatment included either topical arnica 20%, 
5% vitamin K, 1% vitamin K and 0.3% retinol, 20% arnica, or white petrolatum applied BID, 
which was then treated under occlusion BID for 2 weeks. There was less ecchymosis with topical 
arnica compared to controls and similar results with topical vitamin K. However, results of a 
study conducted by Alonso et al (2002), found no difference between topical arnica and control. 
The study evaluated topical arnica (1 × tincture; low homeopathic potency) versus placebo 
applied BID for either 2 weeks before treatment or 2 weeks after treatment of facial 
telangiectases. PDL was applied at the settings of 585 nm and a 5 mm spot size was treated with 
6.3 J/cm2 fluence for all subjects except 1, for whom a 3 mm spot size with a 6.3 J/cm2 fluence 
was used. 
In a double-blind placebo-controlled study conducted by Aleshaki and Polich (2020) 18 bruises 
were mechanically-induced in a single patient by dropping a 3-pound, 2-foot bar of 20 inches 
onto the skin. Blinded investigators evaluated the extent of bruising after either OcuMend (arnica 
and ledum palustre patches) or placebo patches were applied. A statistically significant 
improvement in bruising was observed in the bruises treated with OcuMend compared to 
placebo. To standardize the strength of arnica and method of application, OcuMend patches will 
be used in this study. 
Use of homeopathic preparations of arnica are generally safe and well tolerated (Ianitti et al, 
2016). AEs associated with topical arnica include redness, swelling, and blistering (Leu et al, 
2010). 
Laser Treatment  
Lasers accelerate bruise reduction, by a process known as selective photothermolysis, defined as 
selectively heating hemoglobin and its breakdown products to accelerate bruise resolution (Mayo 
et al, 2013; Morton et al, 2013; Verner et al, 2019). PDL, a vascular laser, will be used as a 
mitigation treatment in this study to reduce bruising after QWO (CCH-aaes) treatment.  
The main target chromophore of PDL (585/595 nm) is oxyhemoglobin (absorption peak: 
577 nm), which results in its effectiveness in hastening the resolution of ecchymoses. Among its 
other uses, PDL has been used to treat vascular lesions and post-operative ecchymoses after 
facial cosmetic procedures (Mayo et al, 2013; Verner et al, 2019).  
Defatta et al (2009), used PDL to treat 20 patients with ecchymosis due to facial cosmetic 
surgeries (ie, cervicofacial rhytidectomy, facial lipocontouring). On post-operative Day 5, half of 
the bruise was treated. A 10-mm spot size was used, with pulse duration of 6 ms, fluence of 
6 J/cm2, and cryogen spray for 30 ms with a 20-ms delay for 3 passes. The patients returned 
48-72 hours later for PDL of the untreated areas under the same parameters, and had a final 
follow-up assessment 48 hours after. Photographs of the treated areas were obtained before and 
after PDL treatment. Ecchymoses captured on the photographs was graded on a scale of 0 to 3 
(with a score of 3 indicating severe ecchymosis) by 3 blinded independent observers. PDL 
treatment resulted in a 63% mean improvement in ecchymosis scores within 48 to 72 hours. The 
authors indicated that in their experience, maximal efficacy of PDL was observed when it was 
performed between 5 and 10 days post-operatively. 


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Karen et al (2010), used PDL to treat 10 patients with ecchymosis due to cosmetic procedures or 
traumatic injury. Each subject served as his or her own control: subjects with 2 ecchymoses had 
1 treated; those with a single lesion had half treated. Photographs were taken before treatment 
and at 24 hours, 48 hours, and 7 days after treatment. Treated bruises were between 24 and 
72 hours old. Subjects received a single treatment with the 595-nm V-Beam PDA (Candela Corp, 
Wayland, Massachusetts) with the following settings: spot size, 10 mm; fluence, 7.5 J/cm2; and 
pulse duration, 6 ms. The Dynamic Cooling Device (Candela Corp) was set at 30 ms with a 
20 ms delay. Two (2) blinded assessors graded bruise severity from 0 to 10 (0, no bruise; 10, 
worst bruising). Forty-eight (48) hours after treatment, the average improvement was 76% and 
37% for treated and untreated lesions, respectively. One (1) week after treatment, treated and 
untreated bruises had improved by 87% and 81%, respectively.  
Accelerated resolution of the treated bruise was observed within 24 hours. Twenty-four (24) 
hours after treatment, the average reduction in the size of the ecchymosis was 62% and 13% for 
treated and untreated bruises, respectively. Forty-eight (48) hours after treatment, the average 
improvement was 76% and 37% for treated and untreated lesions, respectively. The authors 
suggested that the most dramatic response occurred when hemoglobin predominates AEs 
attributed to PDL treatment include mild discomfort and edema (Defatta et al, 2009), transient 
crusting (Karen et al, 2010), and redness and bruising when used at higher settings intended to 
induce bruising (Alonso et al 2002; Leu et al, 2010). 
2.3.4. 
INhance Post-Injection Serum with TriHex Technology® 
INhance Post-Injection Serum with TriHex Technology is a commercial product containing the 
following ingredients: Water/Aqua/Eau, Glycerin, Caprylic/Capric Triglyceride, Propanediol, 
Polyacrylate-13, Lactoferrin, Phosphatidylserine, Palmitoyl Hexapeptide-12, Palmitoyl 
Tripeptide-1, Hexapeptide-11, Acetyl Hexapeptide-38, Acetyl Tetrapeptide-2, Sodium 
Hyaluronate Crosspolymer, Tremella Fuciformis Sporocarp (Silver Ear Mushroom) Extract, 
Peucedanum Graveolens (Dill) Extract, Hydroxymethoxyphenyl Decanone, Dunaliella Salina 
Extract, Betaine, Ledum Palustre (Labrador Tea) Extract, Arnica Montana Flower Extract, 
Phospholipids, Xylitylglucoside, Squalane, Caprylyl Glycol, Anhydroxylitol, Polysorbate 20, 
Xylitol, Butylene Glycol, Sorbitan Isostearate, Ethylhexylglycerin, Caprylhydroxamic Acid, 
Ascorbyl Palmitate, Xanthan Gum, Pentylene Glycol, Glucose, Helianthus Annuus (Sunflower) 
Seed Oil, Tocopherol, Potassium Sorbate, Caprylyl Methicone, Polyisobutene, Lecithin, Sodium 
Hydroxide, Disodium EDTA, Phenoxyethanol. 
The effect of INhance Post-Injection Serum vs a moisturizer was evaluated in a randomized, 
double-blind study of 16 patients who received an induced bruise via mechanical disruption 
(ie, venipuncture, blood removal and reinjection) (Widegrow et al, 2020). Of the patients treated 
with INhance Post-Injection Serum, 81% experienced less bruising after their treatment at Days 
2 and 3 compared to placebo. AEs were not reported. 


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3. 
OBJECTIVES AND ENDPOINTS 
3.1. 
Objectives and Endpoints 
Primary Objective 
Primary Endpoint 
To assess the effect of 
mitigation treatments on 
bruising in the buttocks of 
subjects with cellulite after the 
first treatment of QWO (CCH-
aaes).  
• The proportion of subjects by buttock at each level 
of bruising on the Investigator Assessment of 
Bruising Severity Scale, at Day 4, 3 days after QWO 
(CCH-aaes) injection. This 5-level scale ranges from 
0 to 4, with 0 indicating no bruising or almost none, 
and 4 indicating very severe bruising.  
Secondary Objectives 
Secondary Endpoints 
To assess investigator 
assessment of bruising with 
mitigation treatments in subjects 
with cellulite after the first 
treatment of QWO (CCH-aaes)  
• The proportion of subjects for whom the investigator 
reported an improvement of bruising on the 
mitigation treated buttock on Days 4 and 7 as 
measured on the Investigator-Bruising Improvement 
Scale (I-BIS), a 3-point Likert scale, with a score on 
the higher end of the range indicating improvement 
with treatment.    
• The proportion of subjects by buttock with bruising 
at each level of the Investigator Assessment of 
Bruising Severity Scale, by visit. This 5-level scale 
ranges from 0 to 4, with 0 indicating no bruising or 
almost none, and 4 indicating very severe bruising. 
To assess subject assessment of 
bruising with mitigation 
treatments in subjects with 
cellulite after the first treatment 
of QWO (CCH-aaes). 
• The proportion of subjects treated with QWO (CCH-
aaes) reporting an improvement of bruising on the 
mitigation treated buttock on Days 4 and 7 as 
measured on the Subject-Bruising Improvement 
Scale (S-BIS), a 3-point Likert scale, with a score on 
the higher end of the range indicating improvement 
of bruising with treatment.  
• The proportion of subjects by buttock bothered by 
the appearance of bruising on each of their buttocks 
on the Patient Bother by Bruising Scale, a 4-point 
scale, with a score of 1 indicating not bothered at all, 
and a score of 4, indicating, extremely bothered. 
To assess the effect of 
mitigation treatments on 
bruising in the buttocks of 
subjects with cellulite after the 
first treatment of QWO (CCH-
aaes). 
• The proportion of subjects by buttock with bruising 
at each level of the Investigator Assessment of 
Bruising Severity Scale, by visit. This 5-level scale 
ranges from 0 to 4, with 0 indicating no bruising or 
almost none, and 4 indicating very severe bruising. 


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Secondary Objectives 
Secondary Endpoints 
To assess the level of aesthetic 
improvement of cellulite after 
treatment of QWO (CCH-aaes) 
with and/or without bruising 
mitigation treatment. 
• The proportion of subjects with an improved (+1 or 
better) score on the Investigator-Global Aesthetic 
Improvement Scale (I-GAIS) for either buttock at the 
Day 71 Visit compared to Baseline. The I-GAIS is a 
7-level scale ranging from +3 (very much improved) 
to -3 (very much worse). 
To assess the safety of QWO 
(CCH-aaes) with mitigation 
treatment in subjects with 
cellulite. 
• Percentage of subjects reporting each adverse event 
(AE) and treatment emergent adverse event 
(TEAEs). 
Exploratory Objective 
Exploratory Endpoint 
 
 
 
 
 
• 
 
 
 
 
 
 


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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a Phase 4, multicenter, open-label, multiple dose study to assess the effect of mitigation 
treatments on injection site bruising and safety in adult women with moderate cellulite in the 
buttocks treated with QWO (CCH-aaes). Approximately 75 subjects will be screened in order to 
enroll approximately 48 subjects in 6 cohorts. 
At the Screening Visit, subjects who meet all inclusion criteria and have no exclusion criteria 
according to the investigator’s assessment will be assigned to 1 of 6 treatment cohorts. Subjects 
will be allocated to cohorts using a site specific Mitigation Treatment Assignment Table 
provided by the sponsor. 
Pending site capabilities and available mitigation treatments, each site will administer each 
mitigation treatment, with approximately 1-3 subjects assigned to each mitigation treatment as 
shown in Table 1. Mitigation treatments will be administered at or after the initial treatment 
session of QWO (CCH-aaes). 
Table 1: 
Distribution of Mitigation Treatments  
 
 
QWO (CCH-aaes)a 
Mitigation Treatment 
 
N Left Buttock 
Right Buttock 
Left Buttock 
Right Buttock 
Cohort 1 
8 
Up to 0.84 mg 
Up to 0.84 mg 
None 
Cohort 2 
8 
Up to 0.84 mg 
Up to 0.84 mg 
Compression garment 
Cohort 3 
8 
Up to 0.84 mg 
Up to 0.84 mg 
None 
Instant cold packs  
Cohort 4 
8 
Up to 0.84 mg 
Up to 0.84 mg 
None 
Arnica patches  
Cohort 5 
8 
Up to 0.84 mg 
Up to 0.84 mg 
None 
INhance Post-
Injection Serum with 
TriHex Technology 
Cohort 6 
8 
Up to 0.84 mg 
Up to 0.84 mg 
None 
PDL treatmentb 
a For each subject, an identical dose and injection count of QWO (CCH-aaes) should be administered for the first 
treatment session to each buttock. The number of injections may differ among subjects. 
bPulse dye laser (PDL) may be used at the settings selected according to the investigator’s discretion. 
Eligible subjects will receive up to 0.84 mg of QWO (CCH-aaes) per buttock in both buttocks 
for a total dose of 1.68 mg per treatment session for 3 treatment sessions (Day 1, Day 21 
±3 days, and Day 43 ±3 days). To reduce variance in the bruising observed on the left and right 
buttock of a subject after the first treatment session of QWO (CCH-aaes), each buttock should be 
treated with the same number of QWO (CCH-aaes) injections on Day 1, of up to 12 injections 
per buttock. The number of injections may differ between treatment sessions; 12 injections per 
buttock may be administered during the first treatment session followed by fewer injections per 
buttock during the second and third treatment sessions. The number of injections per buttock per 
subject may differ among subjects. 
Subjects will return to the site approximately on Days 2, 4, 7, and 14 (ie, 1, 3, 6, and 13 days 
after injection on Day 1) for additional evaluations and digital photography obtained with 
standardized parameters. After the first mitigation treatment session, on Days 4 and 7, the effect 
of mitigation treatments on the severity of bruising will be assessed using the I-BIS and the 
Investigator Assessment of Bruising Severity Scale. The effect of mitigation treatments on the 
severity of bruising will be assessed by subjects on the S-BIS and the Patient Bother by Bruising 


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Scale. Safety will be assessed by collecting AEs, and TEAEs and assessing injection site 
reactions in the buttocks throughout the study. 
 
 
At the investigator’s discretion, for the second and third QWO (CCH-aaes) treatment sessions on 
Days 22 and 43, subjects will be permitted to receive the same mitigation treatment to the right 
buttock as received during the first QWO (CCH-aaes) treatment session. The severity of bruising 
will be assessed at each visit. Subject and investigator assessments of satisfaction, aesthetic 
improvement, and digital photography will also be conducted on Days 22 (± 3 days) and 43 
(±3 days). Subjects will return to the site for last study visit on Day 71 for additional investigator 
assessments of bruising and digital photography.   
Subjects will participate in the study for approximately 92 days.  
4.2. 
Scientific Rationale for the Study Design 
The most common AE in previous studies of QWO (CCH-aaes) was injection site bruising 
(QWO Prescribing Information). Ecchymosis that occurs after an injury is generally referred to 
as a bruise (Verner et al, 2019). Bruising after the first treatment of QWO (CCH-aaes) is the 
most robust (ie, greater frequency, greater severity, longest duration) as compared to the bruising 
after the second or third treatments (CSR EN3835-205). Bruising typically resolves within 
21 days.  
The photographic substudy of Study EN3835-205, depicted bruising over time in photocollages, 
Investigators that participated in the investigational studies of QWO (CCH-aaes), and/or 
aesthetic medicine specialists who have viewed these photocollages have expressed interest in 
evaluating the effects of mitigation treatments to reduce QWO (CCH-aaes)-induced bruising. 
Mitigation treatments supported by the literature or commonly used to reduce bruising either 
post-injection or procedures in clinical practice have been selected for evaluation in this study. 
To ensure a balanced approach in the assessment of bruising among the sites and investigators, a 
Mitigation Treatment Assignment Table will be used to assign 1-3 subjects per mitigation 
treatment per site (pending site capabilities, eligible subjects, and available mitigation 
equipment). 
Subjects with Fitzpatrick skin types of I-III are included in this study. This aligns with the 
approach taken by Widegrow et al (2020) in another study conducted evaluating mitigation 
treatments on bruising.  
The endpoints evaluating the effect of the mitigation treatments on bruising will be limited to the 
time period after the first injection of QWO (CCH-aaes) when characterization of bruising of the 
unmitigated buttock is more robust (greater frequency, more severe, and longest duration) than 
after the second and third injections of QWO (CCH-aaes). This will limit confounding 
introduced by the decreased bruising observed over subsequent treatments of QWO (CCH-aaes) 
when interpreting the effects of the mitigation treatments.   
At the investigator’s discretion, for the second and third QWO (CCH-aaes) treatment sessions, 
subjects are permitted to use the same mitigation treatment in the same buttock (as applicable) 
that received mitigation treatment for the first QWO (CCH-aaes) treatment session. 


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4.2.1. 
 
Changes to the Study Design Due to COVID-19 
The COVID-19 public health emergency has disrupted the conduct of clinical research 
throughout the world. At Endo Pharmaceuticals Inc. (Endo), ensuring the safety of clinical study 
subjects is our primary concern. In addition, the integrity of data obtained from clinical studies 
must be ensured. 
To ensure subject safety and protect data integrity Endo will allow remote visits for certain study 
and safety assessments. This is aligned with the FDA Guidance on Conduct of Clinical Trials of 
Medical Products during COVID-19 Public Health Emergency (March 2020, updated 21 
September 2020), 
Additionally, subjects impacted by the health emergency will be allowed to continue in the study 
and complete assessments when the investigational sites re-open as follows: 
• If a subject had received any dose of QWO (CCH-aaes) in the study prior to an 
interruption will be allowed to continue in the study.   
4.3. 
Justification for Endpoints 
The primary endpoint will be the investigator’s assessment of bruising based on observed, in-
person assessments during the first treatment session. The subject will not be able to directly 
view the bruised skin (ie, would have to use reflection in the mirror) and lighting may not be 
standardized. As such subject viewing of the bruise might be less authentic than direct viewing 
by the investigator. 
The effect of mitigation treatments that are bilaterally administered (eg, compression garments) 
will be evaluated by the investigator by comparing bruising on each buttock (both of which 
receive mitigation treatment) vs bruising observed in the control arm (Cohort 1) that is not 
receiving mitigation treatment. Subjects in this group will not be able to compare their bruising 
to bruising on buttocks with no mitigation. 
The effect of unilaterally applied (right buttock only) topical mitigation treatments (ie, arnica 
patches, INhance, PDL treatment) will be assessed by comparing the bruising in the mitigation-
treated buttock to the contralateral buttock that did not receive mitigation treatment. As such, in 
unilateral mitigation treatment cohorts, subjects will serve as their own control. 
4.4. 
Justification for Dose 
The doses of the mitigation treatments selected are based on the published literature and the 
experience of the collaborative investigators. 
During this study, both buttocks will be treated with QWO (CCH-aaes) at the doses described in 
the QWO Prescribing Information. Subjects can receive up to 12 injections of QWO (CCH-aaes) 
to each buttock. For the first treatment session, the number of injections and dose of QWO 
(CCH-aaes) administered to each buttock should be identical.  
4.5. 
End of Study Definition 
A subject is considered to have completed the study if the subject has completed the Day 71 
visit. The end of the study is defined as the completion of the final assessment for the last subject 
enrolled in the study. 


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5. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
5.1. 
Subject Inclusion Criteria 
In order to be eligible to participate in the study, on Screening and/or Day 1, subjects must: 
1. Voluntarily sign and date an informed consent agreement. 
2. Be a female between ≥18 years of age and ≤ 50 years old. 
3. Have both buttocks with: 
a. a CR-PCSS score of 3 (moderate) as reported by the Investigator, and 
b. a Hexsel CSS Subsection D “Grade of laxity, flaccidity, or sagging skin” score of  0 
(absence of laxity, flaccidity, or sagging skin) or 1 (slightly draped appearance). 
4. Have a body mass index between ≥18 and ≤30 kg/m2, and intends to maintain stable body 
weight throughout the duration of the study (a variation of ≤10% from baseline body 
weight is permitted). 
5. Have a Fitzpatrick skin rating of I-III. 
6. Be willing to apply sunscreen before each exposure to the sun while participating in the 
study (ie, Baseline through end of study). 
7. Be judged to be in good health, based upon the investigator’s medical judgement and the 
results of a medical history and physical examination at Screening.  
8. Be willing and able to cooperate with the requirements of the study. 
9. Have ability to read, complete and understand the patient-reported outcomes rating 
instruments in English. 
5.2. 
Subject Exclusion Criteria 
A subject will be excluded from study participation if the subject: 
1. Has any of the following systemic conditions: 
a. Coagulation disorder including but not limited to a Factor II, V, VII, or X deficiency.  
b. Skin pigmentation disorder. 
c. Evidence or history of malignancy (other than excised basal-cell carcinoma) unless 
there has been no recurrence in at least 5 years. 
d. History of keloidal scarring or abnormal wound healing. 
e. 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 
including but not limited to rheumatoid arthritis and/or other rheumatoid disease(s), 
Vitamin K deficiency, or liver diseases. Any questions about concurrent diseases 
should be discussed with the Medical Monitor. 
f. Evidence of clinically significant abnormalities on physical examination or vital 
signs. 
2. Has any of the following local conditions in the buttocks: 
a. History of lower extremity thrombosis or post-thrombosis syndrome. 
b. Vascular disorder (eg, varicose veins, telangiectasia, vasculitis) in area to be treated. 


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c. Inflammation or active infection in the buttocks.  
d. Active cutaneous alteration including rash, eczema, or psoriasis. 
e. Has a tattoo in the buttocks, visible in clinical photographs. 
3. Has skin laxity or linear undulations on either buttock that can be effaced by lifting skin.  
4. Requires the following concomitant medications during the study and cannot discontinue 
these medications within the time specified before QWO (CCH-aaes) treatment. 
a. Antiplatelet medication (clopidogrel [Plavix®] including aspirin at any dose within 
14 days of treatment. 
b. Anticoagulants, such as warfarin (Coumadin®); heparin analogues within 14 days of 
treatment. 
c. Non-steroidal anti-inflammatory drugs (NSAIDS), such as ibuprofen (Motrin®, 
Advil®) and naproxen (Aleve®) 7 days before the study. 
d. Any medications (eg, corticosteroids, certain antidepressants [eg, citalopram, 
fluoxetine], nutritional/homeopathic supplements [eg, fish oil, Vitamin E, omega 3, 
ginko biloba, ginger, St John’s Wart, green tea, ginseng, feverfew, saw palmetto, 
turmeric, bromelain]) or foods (eg, pineapple) that have, or have been reported to 
have anticoagulant effects within 14 days of treatment. 
e. Antibiotics, such as penicillin and cephalosporin within 48 hours of treatment. 
5. Used any of the following for the treatment of cellulite on a buttock within the timelines 
identified below or intends to use any of the following at any time during the study: 
a. Liposuction in a buttock during the 12-month period before injection of QWO 
(CCH-aaes). 
b. Injections (eg, mesotherapy, dermal fillers, biostimulatory fillers); radiofrequency 
device treatments; laser treatment; buttock implant treatment; cryolipolysis; or 
surgery (including subcision and/or powered subcision) within a buttock during the 
12-month period before QWO (CCH-aaes) injection. 
c. Any investigational treatment for cellulite on a buttock during the 12-month period 
before injection of QWO (CCH-aaes). 
d. Endermologie™ or similar treatments in a buttock during the 6-month period before 
injection of QWO (CCH-aaes). 
e. Massage therapy for cellulite within a buttock during the 3-month period before 
injection of QWO (CCH-aaes). 
f. Creams (eg, Celluvera™, TriLastin®) and/or home therapies to prevent or mitigate 
cellulite within a buttock during the 2-week period before QWO (CCH-aaes) 
injection. 
6. Is presently nursing or providing breast milk or intends to do so during the study. 
7. Intends to become pregnant during the study. 
8. Intends to initiate an intensive sport program regimen, exercise program regimen, or 
intensive weight reduction program during the study. 
9. Has recently tanned or intends to use any tanning spray or tanning booths during the 
study. 


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10. Intends to engage in strenuous activity within 48 hours after the first injection of QWO 
(CCH-aaes). 
11. Has received an investigational drug or treatment within 30 days prior to injection of 
QWO (CCH-aaes). 
12. Has a known systemic allergy to collagenase or any other excipient of QWO (CCH-aaes).  
13. Has a known systemic allergy or local sensitivity to any of the mitigation treatments or 
included excipients (ie, arnica patches, INhance Post-injection Serum). 
14. Has received any collagenase treatments at any time prior to treatment in this study. 
15. Was a subject in a previous cellulite clinical study of CCH (EN3835, QWO [CCH-aaes]). 
16. For subjects allocated to PDL treatment  
Subjects will be excluded from PDL treatment if they have any contraindications to PDL 
as indicated in the manufacturer’s documentation, for example but not limited to:  
a. previous exposure to photosensitizing medications, food and/or supplements or other 
photosensitizing agents within 2 weeks of QWO (CCH-aaes) treatment 
b. exposure to Accutane® (isotretinoin) within 6 months of QWO (CCH-aaes) treatment. 
5.3. 
Lifestyle Considerations 
Subjects will be instructed to refrain from strenuous exercise for 48 hours after the first treatment 
with QWO (CCH-aaes).  
Subjects should avoid medications, homeopathic supplements, or foods as advised by the 
physician prior to QWO (CCH-aaes) treatment. 
Subjects should not use any tanning spray or tanning booths during the study. 
5.4. 
Screen Failures 
Screen failures are defined as subjects who consent to participate in this study but do not 
subsequently receive an injection of QWO (CCH-aaes). Screening procedures will be conducted 
on Day -14, prior to receiving QWO (CCH-aaes) injection. If mitigation treatments could not be 
procured within the 14-day Screening Period, subjects can be rescreened after the Screening 
Period. 
Subjects who do not meet all of the eligibility criteria will be deemed a screen failure and the 
following information must be recorded for all subjects who are screen failures: 
• Demography (age, gender, race/ethnicity). 
• Reason for screen failure. 
• Which eligibility criterion was not met. 
• Any AEs (including serious adverse events [SAEs]) experienced by the subject. 


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6. 
STUDY TREATMENT 
Study treatment comprises QWO (CCH-aaes) and mitigation treatments.  
6.1. 
Selection and Marking of Dimples  
To ensure that the contralateral buttock that does not receive mitigation treatment can serve as its 
own control, and that a similar level of injection site bruising will be induced, subjects should 
have a similar number of dimples requiring treatment. Subjects can be treated with up to 12 
injections of QWO (CCH-aaes) on each buttock. The number of injections of QWO (CCH-aaes) 
administered to the right and left buttocks should be identical on Day 1. The number of 
injections may differ between treatment sessions, eg, 12 injections in each buttock in the first 
treatment session followed by fewer injections per buttock at the second and third treatment 
sessions as dimples improve. 
For treatment, the investigator or qualified designee will select up to 12 dimples within each 
treatment area (each buttock) that are well-defined, evident when the subject is standing, and 
suitable for treatment.  
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 1 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. 
6.2. 
Treatment Administration 
6.2.1. 
QWO (CCH-Aaes) 
QWO will be provided by Endo Pharmaceuticals Inc. 
Dosage and Mode of Administration: QWO (CCH-aaes), 0.84 mg, injected subcutaneously per 
buttock with both buttocks treated for a total dose of 1.68 mg. For each buttock, a dose of up to 
0.84 mg of QWO (CCH-aaes) in 3.6 mL will be administered as up to 12 subcutaneous injections 
(0.3-mL injection administered as three 0.1-mL aliquots per injection). There will be 3 treatment 
visits at intervals of approximately 21 days as described in schedule of assessments. 
To induce a similar extent and severity of bruising in each buttock, approximately the same 
number of injections should be administered to the left and to the right buttock. However, the 
number of injections per buttock may differ among treatments. The number of injections 
administered to each buttock on Day 1 must be recorded. The volume and dose of injection at 
each treatment visit will be injected per the QWO Prescribing Information. QWO will be 
provided in cartons containing 1 QWO 1.84-mg single-dose vial and 1 diluent for QWO 8-mL 
single-dose vial. 
6.2.2. 
Mitigation Treatments 
Mitigation treatments will be provided locally by each investigator/subject.  


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At the investigator’s discretion and with consent of the subject, mitigation treatments provided 
after the first treatment session of QWO (CCH-aaes), can be administered after the second and 
third QWO (CCH-aaes) treatment sessions. Mitigation treatments administered after each 
treatment session with QWO (CCH-aaes) will be recorded as concomitant medications (Section 
6.4).  
Cohort 1 will serve as a control and no mitigation treatment will be administered. 
Compression Garments (Cohort 2) 
Subjects will be instructed to wear a commercially available compression garment (ie, SPANX 
Grade 3) after the injection on Day 1, for 24 hours per day for 7 days after the injection  
(Day 1 – 8). Garments may be removed for personal hygiene and when the subject is being 
evaluated at the investigator’s office during study visits. Subjects should be informed that ill-
fitting compression garments may contribute to pain.  
Instant cold packs (Cohort 3) 
Instant cold packs should be applied to the right buttock only for 5-10 minutes immediately 
after the injection of QWO (CCH-aaes) while the subject is lying in prone position. 
Arnica Gel Patches (OcuMend) (Cohort 4) 
 
Subjects will be instructed to apply OcuMend gel patches (arnica montana 50% and ledum 
palustre) immediately after the CCH-aaes injection to the right buttock only BID on Days 1 
and 2 for a total of 4 doses. One or 2 patches per application may be required depending on the 
extent of the bruising. 
INhance Post-Injection Serum with TriHex Technology® (Cohort 5) 
INhance Post-injection Serum will be applied by investigators at the site of injections on Day 1 
on the right buttock only and then by the subject or subject’s associate QID for up to 7 days 
after injection or until resolution of bruising according to the product instructions. The serum is 
available in a small 10-mL tube with a chilled tip. A small amount of the serum will be applied 
on the skin and around the injection site and gently rubbed in using the cooling applicator.  
Pulse Dye Laser Treatment (Cohort 6) 
Investigators will apply laser treatment with PDL to the bruising observed on the right buttock 
only as a single treatment between Days 1 (same day of QWO [CCH-aaes) injection) and Day 7 
after QWO (CCH-aaes) treatment. 
The investigator can adjust laser settings at his/her discretion. Laser settings will be recorded in 
detail to allow comparability across sites. Only select sites will be administering laser treatment. 
6.2.3. 
QWO (CCH-Aaes) Preparation/Handling/Storage 
Vials of 1.84 mg QWO (CCH-aaes) and its diluent (8 mL) will be supplied in the approved 
commercial packaging. QWO (CCH-aaes) and the diluent must be kept in a temperature-
monitored refrigerator (2°C to 8°C). 


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Please refer to the QWO Prescribing Information for complete information regarding 
preparation, handling, and storage. 
6.3. 
Measures to Minimize Bias 
This is an open label study, however, the mitigation treatment for each subject will be assigned 
in a 1:1:1:1:1:1 ratio using a Mitigation Treatment Assignment Table. To ensure a balanced 
approach in the application of mitigation treatments and the assessment of bruising among the 
sites and investigators, 1-3 subjects per site will be assigned to each mitigation treatment 
(pending site capabilities, subjects available, and available mitigation equipment). 
6.3.1. 
Mitigation Treatment Assignment Table 
At Screening, the investigator or designee will refer to the Mitigation Treatment Assignment 
Table to determine which mitigation treatment should be administered.   
The investigator must maintain a subject master log linking the subject identification number to 
the subject’s name. The subject identification number will not be reassigned to another subject in 
this study in the case of study withdrawal. The investigator must follow all applicable privacy 
laws in order to protect a subject’s privacy and confidentiality. Information that could identify a 
subject will be masked on material sent to and/or received by the sponsor.  
6.4. 
Study Treatment Compliance 
All subjects will receive study treatment (QWO [CCH-aaes] and mitigation treatments) 
administered by the investigator at the study site. All dosing information will be recorded for each 
subject visit. Drug inventory will be maintained in the applicable study records for each site. Used 
drug and diluent vials will be disposed of according to site procedures. Unused/unopened drug 
and diluent vials will be returned to the sponsor (or designee) at the end of the study. Accidental 
or intentional overdoses should be reported to the sponsor/designee promptly (see Section 8.5). 
6.5. 
Prior and Concomitant Medications and Procedures 
The start and stop date, dose, unit, frequency, route of administration, and indication for all prior 
(taken within the 30 days prior to the Baseline Visit) and concomitant (taken from the Baseline 
Visit through the Day 71 Visit) medications and nondrug therapies (eg, blood transfusions, 
oxygen supplementation, physical therapy, etc) received will be recorded. Mitigation treatments 
administered after each treatment session of QWO (CCH-aaes) will be recorded as concomitant 
medications. 
6.5.1. 
Prohibited Medications 
During the study, the following treatments are prohibited: 
• Anticoagulants (ie, warfarin [Coumadin] heparin analogues). 
• Antiplatelet medications (eg, clopidogrel [Plavix], aspirin). 
If a prohibited medication or procedure is used during the study, all pertinent information will be 
recorded. The designated study Medical Monitor must be informed immediately so the sponsor 
may determine whether to continue the subject in the study. 


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6.5.2. 
Suggested Concomitant Medications and Procedures 
During the study, acetaminophen will be permitted to treat pain at the injection site as needed. 
Other required concomitant medications may be administered at the investigator’s discretion.  
6.5.3. 
COVID-19 Related Protocol Deviations 
All study assessments conducted outside of the allowed windows outlined in the schedule of 
assessments due to a COVID-19 interruption will be documented as a protocol deviation. 
COVID-19 will be recorded as the reason for these out-of-window assessments. 


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7. 
DISCONTINUATION FROM STUDY TREATMENT AND STUDY 
WITHDRAWAL 
7.1. 
Discontinuation of Study Treatment 
Subjects who discontinue study treatment (QWO [CCH-aaes], or mitigation treatment) or are 
withdrawn from the study for any reason, will be encouraged to complete the remaining study 
visits and evaluations and provide any additional follow-up information as required by the study, 
unless the subject specifically indicates that they will not participate in any further evaluations. 
The date of and reason for study treatment discontinuation will be recorded. 
Permanent study treatment discontinuation is required for any of the following: 
• The subject becomes pregnant during the study. 
Subjects who discontinue from study treatment at any time after the first dose of study treatment 
(QWO [CCH-aaes] and mitigation treatments) will not be replaced. 
7.2. 
Subject Withdrawal from the Study 
Subjects may withdraw from the study at any time at their own request, or may be withdrawn at 
any time at the discretion of the investigator for safety, behavioral, compliance, or administrative 
reasons. The date of and reason for withdrawal will be recorded. 
If the subject withdraws consent for disclosure of future information, the sponsor may retain and 
continue to use any data collected before such withdrawal of consent. If a subject withdraws 
from the study, the subject may request destruction of any samples taken and not tested and the 
investigator must document this in the site study records. 
A subject may be withdrawn from the study for the following medical or administrative reasons: 
• Withdrawal by subject (reason must be specified). 
• An AE. 
• Death. 
• A protocol deviation (reason must be specified, for example: lack of compliance, use 
of a prohibited concomitant medication, etc). 
• Lost to follow-up.  
• Other reasons (reason must be specified, for example: the subject moved, pregnancy, 
investigator decision, sponsor decision to terminate the study, etc). 
If a subject withdraws from the study, all early termination (ET) procedures should be conducted 
as detailed in schedule of assessments. The date a subject withdraws and the reason for 
withdrawal will be recorded in the electronic case report form (eCRF). If, however, a subject 
withdraws consent, no additional procedures are required except the collection of AE 
information. This information should be recorded in the source documentation and the eCRF.  
Subjects who have been withdrawn from the study at any time after the first dose of study 
treatment (QWO [CCH-aaes], mitigation treatments) will not be replaced. 


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7.3. 
Lost to Follow-up 
A subject will be considered lost to follow-up if the subject repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
Subjects lost to follow-up at any time after the first dose of study treatment (QWO [CCH-aaes]) 
and mitigation treatment) will not be replaced. 


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8. 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the schedule of assessments (Section 1.3). 
Adherence to the study design requirements, including those specified in the schedule of 
assessments, is essential and required for study conduct. Protocol waivers or exemptions are not 
allowed. 
Urgent safety concerns should be discussed with the sponsor immediately upon occurrence or 
awareness to determine if the subject should continue study treatment and/or be withdrawn from 
the study. 
All screening evaluations must be completed and reviewed to confirm that potential subjects 
meet all eligibility criteria. The investigator will maintain a screening log to record details of all 
subjects screened and to confirm eligibility or record reasons for screen failure, as applicable. 
Procedures conducted as part of the subject’s routine clinical management and obtained before 
signing of the ICF may be utilized for screening or baseline purposes provided the procedures 
met the protocol-specified criteria and were performed within the time frame defined in the 
schedule of assessments. 
8.1. 
Screening Assessments 
8.1.1. 
Medical History 
Medical history and cellulite history, including all prior procedures to treat cellulite will be 
obtained at the Screening Visit. Medical history will include a review of the following systems: 
general, dermatological, respiratory, cardiovascular, gastrointestinal, genitourinary, 
gynecological, endocrine, musculoskeletal, hematological, neuropsychological, immune 
(allergies), and head, eyes, ears, nose, and throat. Historical and current medical conditions 
including date of last menstrual period for will be recorded.  
History of tobacco and alcohol use (never, current, former) will also be collected. 
Surgical history will include a review of all surgical procedures completed in the prior 5 years 
and any surgery completed at any time in the treatment area. 
8.1.2. 
Physical Examination 
A limited physical examination will include evaluation of height, weight, lungs, heart, abdomen, 
and extremities will be conducted at the Screening Visit. Weight will also be recorded at the 
Day 71/ET visit. 
All examinations will be performed by a physician or health professional listed on the Form 
FDA 1572 and licensed to perform physical examinations. The investigator will review all 
physical exam findings for clinical significance. Any physical examination finding meeting the 
investigator’s criteria for clinical significance will be recorded as an AE or SAE as appropriate. 
8.1.1. 
Vital Signs 
Temperature, pulse, systolic blood pressure, and diastolic blood pressures will be collected at the 
Screening Visit and before the first QWO (CCH-aaes) injection and approximately 30 minutes 
after injection. Pulse and blood pressure will be collected after the subject has been sitting for 
5 minutes. 


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The investigator will review all vital sign values for clinical significance. Any vital sign value 
meeting the investigator’s criteria for clinical significance will be recorded as an AE (or SAE, if 
appropriate). 
8.1.2. 
Fitzpatrick Skin Scale 
The Fitzpatrick Skin Scale is a 6-level scale (levels I-VI) for assessment of skin color and 
propensity for tanning. The skin types range from level I: Pale white skin, blue/hazel eyes, 
blond/red hair, always burns, does not tan to level VI: Dark brown or black skin, never burns, 
always tans darkly. The investigator (or designee) will determine the Fitzpatrick skin type for all 
subjects on Day 1.  
Only subjects with a Fitzpatrick skin rating of I-III at the Screening Visit will be included in the 
study. This aligns with the approach taken by Widegrow et al (2020) in another study conducted 
evaluating mitigation treatments.  
8.1.3. 
Hexsel Cellulite Scale Severity  
The Hexsel CSS is a photonumeric scale used to assess 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 (Hexsel et al, 2009; Nürnberger and Müller, 1978). Each of 
these features is evaluated on a 4-point scale from a low of 0 to a high of 3. For this study, only 
(D) laxity, flaccidity, or sagging skin will be assessed. 
To participate in the study, for each buttock, subjects must have a Baseline Hexsel CSS 
Subsection D must be ‘0’ (absence of flaccidity or sagging skin) or 1 (slightly draped 
appearance) at the Screening Visit. 
8.1.4. 
Clinician Reported Photonumeric Cellulite Severity Scale  
The Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS)-Buttock will be used 
to assess the severity of cellulite of both treatment areas (each buttock, independently). The CR-
PCSS-Buttock is a 5-level photonumeric scale developed specifically for investigators and used 
by the investigator to assess the severity of the subject’s cellulite in each buttock by live 
assessments. The ratings range from 0 (None) to 4 (Severe) with labels and descriptors to aid the 
investigator in the assessments. This assessment should be made while the subject is in the 
standing position with relaxed gluteus muscles. Investigators who are physicians will be trained 
and qualified on the use of the CR-PCSS-prior to assessing any subjects.  
Subjects must have a baseline CR-PCSS rating of ‘3’ (moderate) on each buttock at the 
Screening Visit to be included in the study. 
8.2. 
Efficacy Assessments 
Efficacy assessments will be evaluated at times specified in the schedule of assessments. Below 
is a general description of each of these assessments. Specific instructions and 
questionnaires/forms (where appropriate) will be provided in the Study Operations Manual. 
To ensure subject safety and protect data integrity, Endo, in accordance with the FDA Guidance 
on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency 
(March 2020, updated 21 September 2020), will allow remote visits for certain efficacy 


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assessments. Additionally, subjects impacted by the health emergency will be allowed to 
continue in the study and complete remaining assessments when the investigational sites re-open. 
8.2.1. 
Digital Photography 
At the time points indicated on the schedule of assessments, the investigator or qualified 
designee will photograph bilateral buttocks in a single photograph while the subjects is standing 
in a consistent, standard relaxed pose, with relaxed gluteus muscles using the investigator’s 
digital camera. Photographs of bilateral buttocks will be obtained  
• 
 Before and after marking dimples and injection sites (prior to injections) on Days 1, 
22, and 43. 
• During the Days 2, 4, 7, 14, and 71 visits (end of study/ET) (no dimple or injection 
site markings). 
All photographs taken by the investigator or qualified designee during this study are the property 
of Endo and de-identified images may be utilized for clinical development, scientific 
communication, marketing, regulatory purposes, and/or legal applications as required/desired by 
Endo. 
Digital photographs captured by the investigator will be uploaded to a central repository. Further 
information is provided in the Study Operations Manual. 
Photographs captured by the subject to assess bruising will not be uploaded to a central 
repository and are not the property of Endo. 
8.2.2. 
Investigator Assessment of Bruising Severity Scale 
At the time points indicated on the schedule of assessments, the severity of bruising for each 
buttock will be documented on the Investigator Assessment of Bruising Severity Scale, a 5-point 
photonumeric scale with  
0 = None or almost no bruising 
1 = Mild bruising 
2 = Moderate bruising 
3 = Severe bruising 
4 = Very severe bruising 
The severity of bruising will be documented on the bruising page of the eCRF. 
8.2.3. 
Investigator-Bruising Improvement Scale  
Before and after the first treatment session with QWO (CCH-aaes), at the time points indicated 
on the schedule of assessments, Investigators will complete the I-BIS, a 3-point Likert scale with 
scores on the higher end of the range indicating greater improvement with mitigation treatment. 
Investigators will rate the bruising of the mitigation-treated buttock when compared to the 
untreated (with mitigation treatment) buttock as either: 
1 = Worse (more bruising) 


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2 = Similar 
3 = Improved (less bruising) 
Note: The I-BIS assessment cannot be completed in subjects that either do not receive mitigation 
treatment (Cohort 1) or subjects that receive bilateral mitigation treatment (eg, Cohort 2 – 
compression garments). These subjects do not have only 1 untreated buttock as a comparator. 
8.2.4. 
Investigator-Global Aesthetic Improvement Scale  
The investigator will determine the degree of improvement of each buttock by comparing the 
cellulite from the Day 1 pre-treatment (Baseline) digital image of each buttock to the cellulite 
seen in a live assessment (Table 2). For each buttock, the investigator will provide the rating 
from those below that best represents his/her answer. 
Table 2: 
Investigator-Global Aesthetic Improvement Scale  
Rating 
Response Option 
Description 
+3 
Very much 
improved 
Optimal cosmetic result from treatment of the 
treated dimples 
+2 
Much improved 
Marked improvement in the treated area appearance 
from before treatment, but not completely optimal 
+1 
Improved 
Obvious improvement in the treated area 
appearance from before treatment, but additional 
treatment is indicated 
0 
No change 
The treated area appearance is essentially the same 
as before treatment 
−1 
Worse 
The treated area appearance is worse than before 
treatment 
−2 
Much worse 
Marked worsening in appearance from the initial 
condition 
−3 
Very much worse 
Obvious worsening in appearance from the initial 
condition 
 
8.2.5. 
 
 
 
8.2.6. 
Subject-Bruising Improvement Scale  
Before and after the first treatment session with QWO (CCH-aaes), at the time points indicated 
on the schedule of assessments, subjects will complete the S-BIS, a 3-point Likert scale with 
scores on the higher end of the range indicating greater improvement of bruising with treatment. 


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Subjects will rate the bruising of the QWO (CCH-aaes) mitigation-treated buttock when 
compared to the untreated (ie, meaning the buttock that was not treated with mitigation 
treatment) buttock as either: 
1 = Worse (more bruising)  
2 = Similar 
3 = Improved (less bruising) 
Note: The S-BIS assessment cannot be completed in either subjects that do not receive mitigation 
treatment (Cohort 1) or subjects that receive bilateral mitigation treatment (eg, Cohort 2 – 
compression garments). These subjects do not have only 1 untreated buttock as a comparator. 
8.2.7. 
Patient Bother by Bruising Scale 
At the time points indicated on the schedule of assessments, for each buttock, subjects will 
indicate their level of bother by bruising, on a 4-point scale as follows: 
Thinking about the bruising on your left/right buttock, how bothered are you with the appearance 
of the bruising on your left/right buttock, as either: 
1 = Not at all bothered 
2 = A little bothered 
3 = Moderately bothered 
4 = Extremely bothered 
Subjects may use either a mirror, or photographs captured by the subject or another person with 
the subject’s imaging device (ie, cell phone, digital cameras), or images captured by the 
investigator or designee using the site’s digital photography system. 
Images captured by the investigator or designee using the site’s digital photography system are 
the property of Endo (Section 8.2.1). Photographs taken by the subject will not be uploaded to 
the central repository and are not considered source documentation. 
8.3. 
Safety Assessments 
All safety assessments will be performed at the time points outlined in the schedule of 
assessments. Additional (unscheduled) safety assessments may be performed as needed. 
To ensure subject safety and protect data integrity, Endo, in accordance with the FDA Guidance 
on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency 
(March 2020, updated 21 September 2020), will allow remote visits for certain safety 
assessments. Additionally, subjects impacted by the health emergency will be allowed to 
continue in the study and complete remaining assessments when the investigational sites re-open. 
8.4. 
Adverse Events and Serious Adverse Events 
The definitions of AEs and SAEs can be found in Section 10.2. 
All AEs, including both observed or volunteered problems, complaints, signs or symptoms must 
be recorded, regardless of whether associated with the use of study treatment. Study treatment 
includes QWO (CCH-aaes) and mitigation treatments. This would include AEs resulting from 


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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. 
8.4.1. 
Time Period and Frequency for Collecting Adverse Event and Serious Adverse 
Event Information  
All SAEs and AEs will be collected by the investigator from the time of signing the ICF through 
the Day 71 visit or for 28 days after the last study treatment for those who early terminate. This 
will include any AEs that are ongoing at the time of completion/termination of the study. 
Investigators are not obligated to actively seek AEs and SAEs after conclusion of subject study 
participation. However, if the investigator learns of any SAE, including death, at any time after 
the subject has been discharged from the study, and the investigator considers the event to be 
reasonably related to the study treatment or study participation, the investigator must notify the 
sponsor within 24 hours as described in Section 10.2.4.1.  
All SAEs will be recorded and reported to the sponsor or designee within 24 hours. The 
investigator will submit any updated SAE data to the sponsor within 24 hours of it being 
available. The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and submitting SAE reports are provided in Section 10.2. 
8.4.2. 
Method of Detecting Adverse Events and Serious Adverse Events 
Care will be taken not to introduce bias when detecting AEs and SAEs. Open-ended and 
nonleading verbal questioning of the subject is the preferred method to inquire about AE 
occurrences.  
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 nonleading question such 
as, “How do you feel?” Study site personnel will then record all pertinent information. The study 
treatment compliance record should also be reviewed to detect potential intentional or 
unintentional overdoses.  
In addition, investigators will document observed and elicited AE. 
8.4.3. 
Follow-up of Adverse Events and Serious Adverse Events 
After the initial AE/SAE report, the investigator is required to proactively follow each subject at 
subsequent visits/contacts. All ongoing AEs must be followed until they have resolved or for 
28 days after the subject’s last study treatment, whichever comes first. All SAEs will be followed 
until they have resolved or the condition stabilizes, the event is otherwise explained, or until 
follow-up is no longer possible. Further information on follow-up procedures is provided in 
Section 10.3. 
8.4.4. 
Regulatory Reporting Requirements for Serious Adverse Events 
Prompt notification by the investigator to the sponsor of an SAE due to QWO (CCH-aaes) or 
mitigation treatment is essential so that legal obligations and ethical responsibilities regarding the 
safety of the study treatment under clinical investigation are met. 


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The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of the study treatment under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements regarding safety reporting to 
regulatory authorities, IRBs, and investigators. 
Investigator safety reports must be prepared for suspected, unexpected serious adverse reactions 
(SUSARs) according to local regulatory requirements and sponsor policy, and forwarded to 
investigators as necessary.  
An investigator who receives a SUSAR IND Safety Report describing an SAE or other specific 
safety information (ie, summary or listing of SAEs) from the sponsor will review and then file it 
with their study documentation, and will notify the IRB, if appropriate according to local 
requirements. 
8.4.5. 
Pregnancy 
All pregnancies in subjects identified during or after this study, where the estimated date of 
conception is determined to have occurred during the study or within 28 days of the last study 
treatment in subjects who terminate from the study early, must be reported, followed to 
conclusion, and the outcome reported, even if the subject is discontinued from the study. The 
investigator should report (as outlined above) all pregnancies within 24 hours using the 
Pregnancy Form. Monitoring of the pregnancy should continue until conclusion and follow-up 
information detailing the progress and outcome must be submitted on 1 or more Pregnancy 
Form(s). A Two-Month Follow-up Pregnancy Form detailing the status of the infant should also 
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, or any other serious 
events) must additionally be reported as such using the Serious Adverse Event (SAE)/Reportable 
Event Form (see Section 10.2). Spontaneous miscarriages should also be reported and handled as 
SAEs.  
Subjects will be instructed to immediately notify the investigator of any pregnancies.  
A subject who becomes pregnant must be withdrawn from the study. Should a subject 
discontinue treatment due to pregnancy, alternative treatment (if available) should be arranged 
according to standard of care, as determined by the investigator. Attempts to obtain the 
pregnancy follow-up and pregnancy outcome information detailed above are necessary even if a 
subject discontinues treatment because of pregnancy. 
8.4.6. 
Adverse Events/Serious Adverse Events Experienced by Nonsubjects Exposed to 
Study Treatment 
Nonsubjects are persons who are not enrolled in the study but have been exposed to study 
treatment, including instances of diversion of study treatment. All such AEs/SAEs occurring in 
nonsubjects from such exposure will be reported to the Endo Pharmacovigilance and Risk 
Management Department on the Serious Adverse Event (SAE)/Reportable Event Form 
regardless of whether the event is serious or not. Instructions for completing the form for events 
experienced by nonsubjects will be provided. SAEs occurring in nonsubjects exposed to study 


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treatment will be processed within the same SAE reporting timelines as described in 
Section 10.2. Additionally, the drug accountability source documentation at the site should 
reflect this occurrence. 
8.5. 
Treatment Overdose 
Study treatment overdose is any accidental or intentional use of treatment in an amount higher 
than the dose indicated by the protocol for that subject. Study treatment compliance should be 
reviewed to detect potential instances of overdose (intentional or accidental). 
Any treatment overdose during the study should be noted on the study treatment eCRF.  
An overdose is not an AE per se, however all AEs associated with an overdose should both be 
entered on the AE eCRF and reported using the procedures detailed in Section 10.2, even if the 
events do not meet seriousness criteria. If the AE associated with an overdose does not meet 
seriousness criteria, it must still be reported using the Endo Serious Adverse Event 
(SAE)/Reportable Event Form and in an expedited manner, but should be noted as nonserious on 
the form and the AE eCRF.  
8.5.1. 
Treatment Abuse/Misuse 
AEs associated with misuse or abuse will be appropriately reported as AEs or SAEs, and 
monitored per Section 10.2. 


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9. 
STATISTICAL CONSIDERATIONS AND METHODS 
9.1. 
Sample Size Determination 
The proposed sample size is approximately 48 subjects. The sample size is based on evaluation 
of mitigation treatment in 6 cohorts of approximately 8 subjects each. Five (5) treatment cohorts 
will receive mitigation treatments and 1 treatment cohort will not receiving mitigation treatment. 
9.2. 
Populations for Analysis 
For the purposes of analysis, the following populations are defined: 
Safety Population - The Safety Population is defined as all allocated subjects who have received 
at least 1 injection of QWO (CCH-aaes) with or without mitigation treatment. All demographic 
and baseline characteristic summaries and safety analyses will be based on this population. The 
safety parameters will be summarized using this population. 
Evaluable Population - The Evaluable Population is defined as all allocated subjects who have 
received at least 1 injection of QWO (CCH-aaes) and have at least 1 bruising assessment after 
the first dose of QWO (CCH-aaes). Analyses of the primary and secondary endpoints will be 
summarized using this population. 
9.3. 
Statistical Hypotheses and Analyses 
This section provides a general summary of the statistical methods to be used in analyzing study 
data. A more detailed statistical analysis plan (SAP) will be developed and finalized prior to 
database lock. 
9.3.1. 
Efficacy Analysis 
The primary efficacy and secondary endpoints will be summarized as count and percentage by 
mitigation group. 
In addition, the severity of bruising will be displayed by visit and mitigation group using count 
and percent.
 
9.3.2. 
Safety Analyses 
All subjects who receive at least 1 dose of QWO [CCH-aaes] with or without mitigation 
treatment will be included in the safety analyses. Subjects will be included in the safety analyses 
based on the actual mitigation received. 
9.3.2.1. 
Adverse Events 
AEs will be coded using MedDRA by preferred term within each system organ class. The 
number of AEs and the number of subjects reporting AEs will be listed and summarized 
descriptively by system organ class, preferred term, severity, and causality for each mitigation 
group. Only TEAEs will be included in all summaries. SAEs including death, will be listed.  


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9.4. 
Interim Analysis 
An interim analysis will be conducted at a time point to be determined after at least 25% of 
subjects of the count of total planned subjects have received treatment and completed Day 22 
Visit assessments. 


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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical and Study Oversight Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
This clinical study is designed to comply with the International Council for Harmonisation (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 good 
clinical practice and in accordance with the ethical principles that have their origins in the 
Declaration of Helsinki defined in 21 CFR, 312.120. 
Approval by the IRB 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 or other documentation of 
assurance of appropriate composition per local and national regulations (eg, a Department of 
Health and Human Services [DHHS] Assurance Number will satisfy this requirement for IRBs in 
the US).  
The study protocol, the informed consent form (ICF), advertisements, materials being provided 
to subjects, and amendments (if any) will be approved to IRBs at each study center in 
conformance with ICH E6, CFR Title 21 Part 56, and any other applicable local laws. The 
investigator is responsible for supplying the IRB with a copy of the current QWO Prescribing 
Information. During the course of the study, the investigator will provide timely and accurate 
reports to the IRB on the progress of the study, at intervals not exceeding 1 year (or as 
appropriate), and will notify the IRB of SAEs or other significant safety findings, per the policy 
of the IRB. At the conclusion of the study, the investigator will submit a final report or close out 
report to the IRB and provide a copy to Endo Pharmaceuticals Inc. 
Any amendment to this protocol will be provided to the investigator in writing by Endo. 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. 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.  
The investigator will be responsible for supplying updated safety and/or study information to 
study subjects as it becomes available.  
10.1.2. 
Financial Disclosure 
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 


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responsible for providing information on financial interests during the course of the study and for 
1 year after the completion of the study. 
10.1.3. 
Informed Consent Process 
The ICF must be approved by the sponsor and the IRB before any subject provides consent. The 
investigator will provide the sponsor with a copy of the IRB-approved ICF and a copy of the 
IRB’s written approval before the start of the study. 
The ICF must contain all applicable elements of informed consent and the mandatory statements 
as defined by national and local regulations, including confidentiality.  
If appropriate, the ICF will contain a separate section that addresses the use of remaining 
mandatory samples for optional exploratory research. The investigator or authorized designee 
will explain to each subject the objectives of the exploratory research. Subjects will be told that 
they are free to refuse to participate and may withdraw their consent at any time and for any 
reason during the storage period. A separate signature will be required to document a subject's 
agreement to allow any remaining specimens to be used for exploratory research. Subjects who 
decline to participate in this optional research will not provide this separate signature. 
At Baseline (and at other time as may be required by the study or when changes are made to the 
consent form), subjects will read the consent form(s) and any privacy authorization as required 
by local and national regulations (such as the Health Insurance Portability and Accountability 
Act [HIPAA] authorization form), after being given an explanation of the study. Before signing 
the consent form(s) and the privacy authorization form (if applicable), subjects will have an 
opportunity to ask questions about the study and discuss the contents of these forms with study 
site personnel. The consent/assent process shall be recorded in source documents. 
Subjects must assent understanding of and voluntarily sign these forms in compliance with ICH 
Good Clinical Practice and all applicable national and international regulations, before 
participating in any study-related procedures. Subjects will be made aware that they may 
withdraw from the study at any time for any reason.  
All versions of each subject's signed ICF must be kept on file by the site for possible inspection by 
regulatory authorities and the sponsor. Signed copies of the consent form(s) and the privacy 
authorization form, if applicable, will be given to the subject.  
The subjects will be made aware of their right to see and copy their records related to the study 
for as long as the investigator has possession of this information. If the subject withdraws 
consent and/or HIPAA authorization, the investigator can no longer disclose health information, 
unless it is needed to preserve the scientific integrity of the study. 
10.1.4. 
Data Protection 
Study subjects will be assigned a unique identifier by the sponsor or designee. Any subject 
records or datasets that are transferred to the sponsor will contain the identifier only; subject 
names or any information which would make the subject identifiable will not be transferred.  
The subject must be informed that his/her personal study-related data will be used by the sponsor 
in accordance with local data protection law. The level of disclosure (in accordance with local 
and/or national law) must also be explained to the subject.  


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The subject must be informed that his/her medical records may be examined by Clinical Quality 
Assurance auditors or other authorized personnel appointed by the sponsor, by appropriate IRB 
members, and by inspectors from regulatory authorities. 
10.1.5. 
Dissemination of Clinical Study Data 
Aggregate results data will be provided to the sites that actively enrolled subjects into this study 
after the clinical study report is finalized. 
Study results and de-identified individual subject data will be released as required by local and/or 
national regulations. 
10.1.6. 
Data Quality Assurance 
Steps to assure the accuracy and reliability of data include the selection of qualified investigators 
and appropriate study centers, review of protocol procedures with the 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 noncompliance 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 in a timely fashion and will be 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, 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. 
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 for inspection and copying, in keeping with national and local regulations. 
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. 
10.1.7. 
Source Documents 
All subject information will be documented on source documentation (ie, paper or eCRF). 
Further information regarding documentation will be provided in the Study Operations Manual. 
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.  


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The investigator shall retain and preserve 1 copy of all data collected or databases generated in 
the course of the study, specifically including but not limited to those defined by Good Clinical 
Practice as essential.  
10.1.8. 
Study and Site Closure 
The sponsor has the right to suspend or terminate the study at any time. The study may be 
suspended or terminated for any reason. 
10.1.9. 
Publication Policy 
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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10.2. 
Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up and Reporting 
10.2.1. 
Definitions 
An AE is any unfavorable or unintended change in body structure (signs), body function 
(symptoms), laboratory result (eg, chemistry, electrocardiogram, X-ray, etc), or worsening of a 
pre-existing condition associated temporally with the use of the study treatment (QWO [CCH-
aaes]) or mitigation treatments) whether or not considered related to the study treatment. AEs 
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 TEAE is any condition that was not present prior to treatment with study treatment 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). 
An 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 preplanned surgery, procedure, or drug therapy does not constitute an SAE).  
• Results in permanent or substantial disability (permanent or substantial disruption of 
one’s ability to conduct normal life functions). 
• Is a congenital anomaly/birth defect (in offspring of a subject using the study 
treatment 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 any cancer, 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.  


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10.2.2. 
Relationship to Study Treatment 
In this study, study treatment will comprise QWO (CCH-aaes), and mitigation treatments. 
The degree of “relatedness” of the AE to the study treatment must be described using the 
following scale:  
• Not related indicates that the AE is definitely not related to the study treatment. 
• Unlikely related indicates that there are other, more likely causes and study 
treatment is not suspected as a cause. 
• Possibly related indicates that a direct cause and effect relationship between study 
treatment 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 treatment. 
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. 
10.2.3. 
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. 
10.2.4. 
Reporting Adverse Events and Serious Adverse Events 
10.2.4.1. Reporting Adverse Events 
Throughout the study, AEs will be documented in existing medical records at the site either in 
paper or electronic format 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 treatment; relationship will be 
classified as not related, unlikely related, possibly related, or probably related.  


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10.2.4.2. 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 Serious Adverse 
Event (SAE)/Reportable Event Form within 24 hours of first becoming aware of the SAE. 
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 Endo Serious Adverse Event (SAE)/Reportable Event Forms should be sent to 
 or faxed to 
.  
The sponsor will determine whether the SAE must be reported within 7 or 15 days to regulatory 
authorities in compliance with local and regional law. If so, the sponsor (or the sponsor’s 
representative) will report the event to the appropriate regulatory authorities. The investigator 
will report SAEs to the IRB per their IRB policy. 
10.2.4.3. Follow-up Procedures for Serious Adverse Events 
To fully understand the nature of any SAE, obtaining follow-up information is important. 
Whenever possible, relevant medical records such as discharge summaries, medical 
consultations, and the like should be obtained. In the event of death, regardless of cause, all 
attempts should be made to obtain the death certificate and any autopsy report. These records 
should be reviewed in detail, and the investigator should comment on any event, lab abnormality, 
or any other finding, noting whether it should be considered a serious or non-serious AE, or 
whether it should be considered as part of the subject’s history. In addition, all events or other 
findings determined to be SAEs should be identified on the follow-up SAE form and the 
investigator should consider whether the event is related or not related to study treatment. All 
events determined to be nonserious should be reported on the eCRF. 
 
10.3. 
Appendix 3: Contraceptive Guidance and Collection of Pregnancy Information 
See Section 5, and Section 8.4.5. 
10.4. 
Abbreviations 
Abbreviation  
Explanation 
AE 
Adverse event 
BID 
Twice daily 
CCH 
Collagenase clostridium histolyticum 
CSS 
Cellulite Severity Scale 
CR-PCSS 
Clinician Reported Photonumeric Cellulite Severity Scale 
eCRF 
Electronic case report form 
ET 
Early termination 
HIPAA 
Health Insurance Portability and Accountability Act 
I-BIS 
Investigator-Bruising Improvement Scale 
I-GAIS 
Investigator-Global Aesthetic Improvement Scale 
ICF 
Informed consent form 
 
International Council on Harmonisation 
ICH 
Institutional Review Board 
PDL 
Pulse dye laser 
QID 
Four times daily 


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Abbreviation  
Explanation 
SAE 
Serious adverse event 
S-BIS 
Subject-Bruising Improvement Scale 
SUSAR 
Suspected, unexpected serious adverse reactions 
TEAE 
Treatment emergent adverse event  
 


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11. 
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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12. 
REFERENCES 
Alesahki J, Polich NJ. A double-blind placebo controlled trial of arnica montana and ledum 
palustre for the reduction of ecchymosis. Available at www.cearna.com. Accessed 11 November 
2020. 
Alonso D, Lazarus MC, Baumann L. Effects of topical arnica gel on post-laser treatment bruises. 
Surg. 2002;28(8):686-8. doi: 10.1046/j.1524-4725.2002.02011.x 
Brennan C. Stop "cruising for a bruising": mitigating bruising in aesthetic medicine. Plast Surg 
Nurs. 2014;34(2):75-81. doi:10.1097/PSN.0000000000000040 
Chaiet SR, Marcus BC. Perioperative Arnica montana for reduction of ecchymosis in rhinoplasty 
surgery. Ann Plast Surg. 2016;76(5):477-82. doi: 10.1097/SAP.0000000000000312. 
DeFatta RJ, Krishna S, Williams EF 3rd. Pulsed-dye laser for treating ecchymoses after facial 
cosmetic procedures. Arch Facial Plast Surg. 2009;11(2):99-103. doi: 
10.1001/archfacial.2008.538 
Endo Pharmaceuticals, Inc. A phase 2 open-label extension study of EN3835 in the treatment of 
edematous fibrosclerotic panniculopathy [Clinical Study Report EN3835-202]. Malvern, PA; 23 
April 2019. 
Endo Pharmaceuticals, Inc. A phase 2 open-label study of EN3835 in the treatment of edematous 
fibrosclerotic panniculopathy [Clinical Study Report EN3835-205]. Malvern, PA 02 July 2019. 
Endo Pharmaceuticals, Inc. A phase 3, randomized, double-blind, placebo-controlled study of 
EN3835 in the treatment of edematous fibrosclerotic panniculopathy [Clinical Study Report 
EN3835-302]. Malvern, PA 28 June 2019. 
Endo Pharmaceuticals, Inc. A phase 3, randomized, double-blind, placebo-controlled study of 
EN385 in the treatment of edematous fibrosclerotic panniculopathy [Clinical Study Report 
EN3835-303]. Malvern, PA 15 July 2019.  
Gladfelter J. Compression garments 101. Plast Surg Nurs. 2007 27(2):73-7; doi: 
10.1097/01.PSN.0000278235.87964.f5. 
Hexsel DM, Dal’Forno T, Hexsel CL. A validated photonumeric cellulite severity scale. J Eur 
Acad Dermatol Venereol. 2009;23(5):523-528. 
Iannitti T, Morales-Medina JC, Bellavite P,et al. Effectiveness and safety of arnica montana in 
post-surgical setting, pain and inflammation. Am J Ther. 2016;23(1):e184-97. doi: 
10.1097/MJT.0000000000000036.  
Karen JK, Hale EK, Geronemus RG. A simple solution to the common problem of ecchymosis. 
Arch Dermatol. 2010;146(1):94-5. doi: 10.1001/archdermatol.2009.343. 
Knackstedt R, Gatherwright J. Perioperative homeopathic arnica and bromelain: Current results 
and future directions. Ann Plast Surg. 2020;84(3):e10-e15. doi: 
10.1097/SAP.0000000000002043 
Kotlus BS, Heringer DM, Dryden RM. Evaluation of homeopathic Arnica montana for 
ecchymosis after upper blepharoplasty: a placebo-controlled, randomized, double-blind study. 
Ophthalmic Plast Reconstr Surg. 2010;26(6):395-7. doi: 10.1097/IOP.0b013e3181cd93be. 


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Lee HS, Yoon HY, Kim IH, Hwang SH. The effectiveness of postoperative intervention in 
patients after rhinoplasty: a meta-analysis. 2017;274(7):2685-2694. doi:10.1007/s00405-017-
4535-6 
Leu S, Havey J, White LE, et al. Accelerated resolution of laser-induced bruising with topical 
20% arnica: a rater-blinded randomized controlled trial. Br J Dermatol. 2010;163(3):557-63. doi: 
10.1111/j.1365-2133.2010.09813.x. 
Mayo TT, Khan F, Hunt C, et al. Comparative study on bruise reduction treatments after bruise 
induction using the pulsed dye laser. Dermatol Surg. 2013;39(10):1459-64. doi: 
10.1111/dsu.12293. Epub 2013 Jul 30 
Morton LM, Smith KC, Dover JS, Arndt KA. Treatment of purpura with lasers and light sources. 
J Drugs Dermatol. 2013;12(11):1219-1222. 
Nestor MS, Ablon GR, Stillman MA. The use of a contact cooling device to reduce pain and 
ecchymosis associated with dermal filler injections. J Clin Aesthet Dermatol. 2010;3(3):29-34. 
Nürnberger F, Müller G. So-called cellulite: an invented disease. J Dermatol Surg Oncol. 
1978;4(3):221-229. 
QWOTM. Prescribing Information. Endo Global Aesthetics Limited; 07/2020. Accessed  05 
October 10, 2020. www.qwo.com 
Simsek G, Sari E, Kilic R, et al. Topical application of arnica and mucopolysaccharide 
polysulfate attenuates periorbital edema and ecchymosis in open rhinoplasty: A randomized 
controlled clinical study. Plast Reconstr Surg. 2016;137(3):530e-535e. doi: 
10.1097/01.prs.0000479967.94459.1c 
Swenson C, Swärd L, Karlsson J. Cryotherapy in sports medicine. Scand J Med Sci Sports. 
1996;6(4):193-200. doi:10.1111/j.1600-0838.1996.tb00090.x 
Totonchi A, Guyuron B. A randomized, controlled comparison between arnica and steroids in 
the management of postrhinoplasty ecchymosis and edema. Plast Reconstr Surg. 
2007;120(1):271-4. doi: 10.1097/01.prs.0000264397.80585.bd. 
van Exsel DC, Pool SM, van Uchelen JH, et al. Arnica ointment 10% does not improve upper 
blepharoplasty outcome: A randomized, placebo-controlled trial. Plast Reconstr Surg. 
2016;138(1):66-73. doi: 10.1097/PRS.0000000000002249 
Verner I, Prag Naveh H, Bertossi D. Treatment of injection-induced ecchymoses with light/laser-
assisted technology. Dermatol Ther. 2019 ;32(3):e12861. doi: 10.1111/dth.12861. Epub 2019 
Mar 28 
Widegrow AD, Jacob C, Palm MD, et al. Developing a topical adjunct to injectable procedures. J 
Drugs Dermatol. 2020 19(4):398-404. doi: 10.36849/JDD.2020.5016 32272517. 
 
 

SAP_001.pdf: 
Statistical Analysis Plan (SAP) Module 1 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 1
SAP MODULE 1 – DETAILED STATISTICAL METHODOLOGY
STUDY EN3835-401
MOBI: A PHASE 4, OPEN-LABEL STUDY TO ASSESS EFFECTS OF 
MITIGATION TREATMENTS ON BRUISING OF CCH-AAES 
TREATMENT OF BUTTOCK CELLULITE IN ADULT FEMALES
Version 1.0
February 10, 2021
Endo Pharmaceuticals Inc.
1400 Atwater Drive
Malvern, PA 19355
USA
NCT #NCT04677712


Statistical Analysis Plan (SAP) Module 1 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 2
TABLE OF CONTENTS
TABLE OF CONTENTS............................................................................................................2
LIST OF TABLES......................................................................................................................6
LIST OF ABBREVIATIONS AND DEFINITIONS ...................................................................7
1.
STUDY OBJECTIVE...............................................................................................8
2.
STUDY DESIGN AND MEASURES ......................................................................8
2.1.
Inclusion Criteria....................................................................................................12
2.2.
Exclusion Criteria...................................................................................................12
2.3.
Selecting and Marking of Dimples..........................................................................14
2.4.
Treatment Administration.......................................................................................15
2.4.1.
QWO (CCH-aaes) ..................................................................................................15
2.4.2.
Mitigation Treatments.............................................................................................15
2.4.2.1.
Compression Garments (Cohort 2)..........................................................................15
2.4.2.2.
Instant cold packs (Cohort 3)..................................................................................15
2.4.2.3.
Arnica Gel Patches (OcuMend) (Cohort 4) .............................................................15
2.4.2.4.
INhance Post-Injection Serum with TriHex Technology (Cohort 5)........................16
2.4.2.5.
Pulse Dye Laser Treatment (Cohort 6)....................................................................16
2.5.
Measures to Minimize Bias.....................................................................................16
2.6.
Digital Photographs ................................................................................................16
2.7.
Investigator Assessment Ratings.............................................................................16
2.7.1.
Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS)...................16
2.7.2.
Hexsel Cellulite Severity Scale (CSS).....................................................................17
2.7.3.
Investigator Assessment of Bruising Severity Scale................................................18
2.7.4.
Investigator Bruising Improvement Scale (I-BIS) ...................................................18
2.7.5.
Investigator-Global Aesthetic Improvement Scale (I-GAIS) ...................................18
2.8.
Subject Assessment Ratings....................................................................................19
2.8.2.
Subject Bruising Improvement Scale (S-BIS) .........................................................19
2.8.3.
Patient Bother by Bruising Scale.............................................................................19
2.9.
Skin Assessment (Fitzpatrick Scale) .......................................................................20
2.10.
Weight, Height, and BMI........................................................................................20
2.11.
Adverse Events.......................................................................................................20


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2.12.
Medical History......................................................................................................21
2.13.
Physical Examination .............................................................................................21
2.14.
Vital Signs..............................................................................................................21
2.15.
Pregnancy...............................................................................................................22
2.16.
Prior and Concomitant Medications and Procedures ...............................................22
2.16.1.
Prohibited Medications...........................................................................................22
2.16.2.
Suggested Concomitant Medications and Procedures..............................................22
2.17.
COVID-19 Related Protocol Deviations .................................................................22
3.
STUDY PARAMETERS........................................................................................23
3.1.
Subject Disposition.................................................................................................23
3.2.
Early Termination Visit Assessments......................................................................23
3.3.
Study Treatment .....................................................................................................23
3.3.1.
QWO (CCH-aaes) Assessments..............................................................................23
3.3.2.
Mitigation Assessments ..........................................................................................24
3.3.3.
Cohorts...................................................................................................................24
3.4.
Efficacy Parameters................................................................................................24
3.4.1.
Investigator Bruising Severity Scale .......................................................................24
3.4.1.1.
Investigator Bruising Severity Scale Rating ............................................................24
3.4.1.2.
Baseline Investigator Bruising Severity Scale Rating..............................................24
3.4.1.3.
Change from Baseline Investigator Bruising Severity Scale Rating.........................24
3.4.2.
I-GAIS ...................................................................................................................25
3.4.2.1.
I-GAIS Rating ........................................................................................................25
3.4.2.2.
One-Level I-GAIS Responder.................................................................................25
3.4.3.
I-BIS Rating ...........................................................................................................25
3.4.4.
S-BIS Rating ..........................................................................................................25
3.4.5.
Patient Bothered by Bruising Scale Rating..............................................................25
3.5.
Safety Parameters ...................................................................................................26
3.5.1.
Adverse Events and Treatment-Emergent Adverse Events......................................26
3.5.1.1.
Adverse Event Duration..........................................................................................26


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3.5.1.2.
Intensity of Adverse Events ....................................................................................26
3.5.1.3.
Relationship to QWO (CCH-aaes) ..........................................................................26
3.5.1.4.
Relationship to Mitigation Treatment......................................................................26
3.5.1.5.
Action Taken with QWO (CCH-aaes) and Mitigation Treatments...........................27
3.5.2.
Vital Signs..............................................................................................................27
3.6.
Other Parameters ....................................................................................................27
3.6.1.
Medical History......................................................................................................27
3.6.2.
Prior/Concomitant Medications and Procedures......................................................27
4.
ANALYSIS POPULATIONS.................................................................................28
4.1.
Safety Population....................................................................................................28
4.2.
Evaluable Population..............................................................................................28
5.
STATISTICAL METHODS...................................................................................28
5.1.
Overview................................................................................................................28
5.2.
Missing Data Handling ...........................................................................................29
5.3.
Subject Disposition.................................................................................................29
5.4.
Protocol Deviations ................................................................................................29
5.5.
Demographics and Baseline Characteristics ............................................................29
5.6.
Medical and Surgical History..................................................................................30
5.7.
Efficacy Evaluation ................................................................................................30
5.7.1.
Overview of Treatment...........................................................................................30
5.7.1.1.
QWO (CCH-aaes) ..................................................................................................30
5.7.1.2.
Mitigation...............................................................................................................30
5.7.2.
Primary Endpoint and Secondary Endpoints – Bruising Level ................................31
5.7.3.
Secondary Endpoints – Improvement of Bruising ...................................................31
5.7.4.
Secondary Endpoints – Patient Bothered by Bruising..............................................31
5.7.5.
Exploratory Endpoints –
5.8.
Safety Evaluation....................................................................................................32
5.8.1.
Adverse Events.......................................................................................................32
5.8.1.1.
Adverse Event Conventions....................................................................................33
5.8.2.
Weight and BMI.....................................................................................................34
5.8.3.
Vital Signs..............................................................................................................34
5.8.4.
Prior and Concomitant Medications and Procedures ...............................................34
6.
DERIVED VARIABLES........................................................................................34


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6.1.
Subject Level Variables..........................................................................................34
6.2.
Safety Variables .....................................................................................................35
6.2.1.
Adverse Events.......................................................................................................35
6.3.
Imputation of Partial Dates .....................................................................................36
6.4.
Relative Study Day.................................................................................................36
6.5.
Conventions and Algorithms...................................................................................36
6.5.1.
Summary Tables/Subject Listings Conventions ......................................................36
7.
INTERIM ANALYSES..........................................................................................37
8.
SAMPLE SIZE DETERMINATIONS....................................................................37
9.
TABLES, LISTINGS, AND GRAPH SHELLS ......................................................37
10.
CHANGE FROM PROTOCOL..............................................................................37
11.
REVISION HISTORY ...........................................................................................38
12.
REFERENCES.......................................................................................................38
13.
TABLES, LISTINGS, AND GRAPH SHELLS ......................................................38


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LIST OF TABLES
Table 1: 
Distribution of Mitigation Treatments.......................................................................8
Table 2: 
Study EN3835-401 Schedule of Assessments .........................................................10
Table 3: 
Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS)...................17
Table 4: 
Hexsel CSS (D) laxity, flaccidity or sagging of skin ...............................................17
Table 5: 
Investigator Bruising Severity Scale .......................................................................18
Table 6:
Investigator Bruising Improvement Scale (I-BIS) ..................................................18
Table 7: 
Investigator Global Aesthetic Improvement Scale (I-GAIS)....................................19
Table 8: 
Subject Bruising Improvement Scale (S-BIS) .........................................................19
Table 9: 
Patient Bother by Bruising Scale.............................................................................20
Table 10: Fitzpatrick Scale .....................................................................................................20
Table 11: Subject Level Derived Dataset Variables ................................................................34
Table 12: Adverse Event Variables by Event..........................................................................35
Table 13: Adverse Event Variables by Subject .......................................................................35
Table 14: Changes from Protocol ...........................................................................................37
Table 15: Revision History.....................................................................................................38


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LIST OF ABBREVIATIONS AND DEFINITIONS
Abbreviation
Definition
AE
Adverse event
ATC
Anatomical therapeutic chemical
BID
Twice daily
BIS
Bruising Improvement Scale
BMI
Body mass index
CCH
Collagenase clostridium histolyticum
cm
centimeters
CR-PCSS
Clinician Reported Photonumeric Cellulite Severity Scale
CSS
Cellulite Severity Scale
eCRF
Electronic case report form
ET
Early termination
EN3835
Purified lyophilized clostridial collagenase
GAIS
Global Aesthetic Improvement Scale
IA
Interim Analysis
I-BIS
Investigator – Bruising Improvement Scale
ICF
Informed consent form
ICH
International Council on Harmonisation
I-GAIS
Investigator Global Aesthetic Improvement Scale
kg
kilogram
m
meters
MedDRA
Medical Dictionary for Regulatory Activities
mg
milligrams
mL
milliliters 
NSAIDS
Non-steroidal anti-inflammatory drugs
PDL
Pulse Dye Laser
PR-PCSS
Patient Reported Photonumeric Cellulite Severity Scale
QID
Four times daily
SAE
Serious adverse event
SAP
Statistical Analysis Plan
S-BIS
Subject – Bruising Improvement Scale
SD
Standard deviation
TEAE
Treatment-emergent adverse event
WHO
World Health Organization


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1.
STUDY OBJECTIVE
The primary objective of this study is to assess the effect of mitigation treatments on bruising in 
the buttocks of subjects with cellulite after the first treatment of QWO (CCH-aaes).
The secondary objectives of this study are:

To assess both investigator and subject assessment of bruising with mitigation treatments 
in subjects with cellulite after the first treatment of QWO (CCH-aaes);

To assess the level of aesthetic improvement of cellulite after treatment of QWO (CCH-
aaes) with and/or without bruising mitigation treatment;

To assess the safety of QWO (CCH-aaes) with mitigation treatment in subjects with 
cellulite.
 
 
2.
STUDY DESIGN AND MEASURES
This study is a Phase 4, multicenter, open-label, multiple dose study to assess the effect of 
mitigation treatments on injection site bruising and safety in adult women with moderate cellulite 
in the buttocks treated with QWO (CCH-aaes). Approximately 75 subjects will be screened in 
order to enroll approximately 48 subjects in 6 cohorts.
At the Screening Visit, subjects who meet all inclusion criteria and have no exclusion criteria 
according to the investigator’s assessment will be assigned to 1 of 6 treatment cohorts. Subjects 
will be allocated to cohorts using a site-specific Mitigation Treatment Assignment Table 
provided by the sponsor.
Pending site capabilities and available mitigation treatments, each site will administer each 
mitigation treatment, with approximately 1-3 subjects assigned to each mitigation treatment as 
shown in Table 1. Mitigation treatments will be administered at or after the initial treatment 
session of QWO (CCH-aaes).
Table 1: 
Distribution of Mitigation Treatments
QWO (CCH-aaes)a
Mitigation Treatment
N
Left Buttock
Right Buttock
Left Buttock
Right Buttock
Cohort 1
8
Up to 0.84 mg
Up to 0.84 mg
None
Cohort 2
8
Up to 0.84 mg
Up to 0.84 mg
Compression garment
Cohort 3
8
Up to 0.84 mg
Up to 0.84 mg
None
Instant cold packs
Cohort 4
8
Up to 0.84 mg
Up to 0.84 mg
None
Arnica patches
Cohort 5
8
Up to 0.84 mg
Up to 0.84 mg
None
INhance Post-Injection 
Serum with TriHex 
Technology
Cohort 6
8
Up to 0.84 mg
Up to 0.84 mg
None
PDL Treatmentb
aFor each subject, an identical dose and injection count of QWO (CCH-aaes) should be administered for the first treatment 
session to each buttock.  The number of injections may differ among subjects.
bPulse dye laser (PDL) may be used at the settings selected according to the investigator's discretion.


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Eligible subjects will receive up to 0.84 mg of QWO (CCH-aaes) per buttock in both buttocks 
for a total dose of 1.68 mg per treatment session for 3 treatment sessions (Day 1, Day 21 ±3 
days, and Day 43 ±3 days). To reduce variance in the bruising observed on the left and right 
buttock of a subject after the first treatment session of QWO (CCH-aaes), each buttock should be 
treated with the same number of QWO (CCH-aaes) injections on Day 1, of up to 12 injections 
per buttock. The number of injections may differ between treatment sessions; 12 injections per 
buttock may be administered during the first treatment session followed by fewer injections per 
buttock during the second and third treatment sessions. The number of injections per buttock per 
subject may differ among subjects.
Subjects will return to the site on Days 2, 4, 7, and 14 (ie, 1, 3, 6, and 13 days after injection on 
Day 1) for additional evaluations and digital photography obtained with standardized parameters. 
After the first mitigation treatment session, on Days 4 and 7, the effect of mitigation treatments 
on the severity of bruising will be assessed using the Investigator Bruising Improvement Scale 
(I-BIS) and the Investigator Assessment of Bruising Severity Scale. The effect of mitigation 
treatments on the severity of bruising will be assessed by subjects on the Subject Bruising 
Improvement Scale (S-BIS) and the Patient Bother by Bruising Scale. Safety will be assessed by 
collecting adverse events (AEs) and treatment-emergent adverse events (TEAEs) and assessing 
injection site reactions in the buttocks throughout the study. 
 
At the investigator’s discretion, for the second and third QWO (CCH-aaes) treatment sessions on 
Days 22 and 43, subjects will be permitted to receive the same mitigation treatment to the right 
buttock as received during the first QWO (CCH-aaes) treatment session. The severity of bruising 
will be assessed at each visit. Subject and investigator assessments of satisfaction, aesthetic 
improvement, and digital photography will also be conducted on Days 22 (± 3 days) and 43 (±3 
days). Subjects will return to the site for last study visit on Day 71 for additional investigator 
assessments of bruising and digital photography.
Subjects will participate in the study for approximately 92 days.
Table 2 contains the schedule of assessments.


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Table 2: 
Study EN3835-401 Schedule of Assessments
Procedures
Screening Period
Treatment Period
Follow-Up Period
Day -14
Day 1
(Baseline)
Day 2
Day 4
Day 7
Day 14
Day 22 
(± 3d)
Day 43 
(± 3d)
Day 71/ET (+7d)
Informed consent
X
Inclusion/exclusion criteria
X
Medical history/surgical history/cellulite history 
including previous treatments
X
Prior/concomitant medications/procedures 
(including all prior medications/procedures for 
cellulite)
X
X
X
X
X
X
X
X
X
Physical examination (including height)
X
Weight
X
X
Fitzpatrick skin type
X a
Vital signs
X
X b
Digital photographyc
X
X
X
X
X
X d
X d
X
Cohort assignment
X e
QWO (CCH-aaes) administration
X
X
X
Subject Assessments
 
 
Subject-Bruising Improvement Scale (S-BIS)
X
X
X
X
X d
Patient Bother by Bruising Scale g
X
X
X d
Investigator Assessments
Hexsel Cellulite Severity Scale (CSS) Subsection 
D
X h
Clinician-Reported Photonumeric Cellulite 
Severity Scale (CR-PCSS)
X i
Selection and marking of dimples to be treated 
with both buttocks
X c
X d
X d
Investigator Assessment of Bruising Severity 
Scale
X
X
X
X
X
X d
Investigator- Bruising Improvement Scale (I-
BIS) j
X
X
X
X
X d
Investigator- Global Aesthetic Improvement 
Scale (I-GAIS)
X d
X
X


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Table 2: 
Study EN3835-401 Assessments (Continued)
Procedures
Screening Period
Treatment Period
Follow-Up Period
Day -14
Day 1
(Baseline)
Day 2
Day 4
Day 7
Day 14
Day 22 
(± 3d)
Day 43 
(± 3d)
Day 71/ET (+7d)
Mitigation Treatment Cohorts
Compression garments
X k,p
Instant cold packs to the right buttock only
X l,p
Arnica patches (OcuMend®) to the right buttock 
only
X m,p
INhance Post-Injection Serum with TriHex 
Technology® to the right buttock only
X n,p
Pulse dye laser (PDL) treatment to the right 
buttock only
X o,p
Injection site reactions/local tolerability in each 
buttock treated
X
X
X
X
X
X
X
X
Adverse events (AEs)
X q
a Subjects with a Fitzpatrick skin rating of I-III will be included.
b Before injection and approximately 30 minutes after injection. Pulse and blood pressure should be collected after the subject has been sitting for 5 minutes.
c Buttocks will be photographed before and after injection site and dimple marking on Days 1, 22, and 43. Buttocks will also be photographed during the Days 2,
4, 7, 14, and 71 visits (ET) (no dimple or injection site markings).
d. Before injection.
e Subjects will be assigned to 1 of 6 cohorts according to a site specific Mitigation Treatment Assignment Table. Cohort 1 = no mitigation treatment;
Cohorts 2-6 = mitigation treatments
f Before QWO (CCH-aaes) injection, and 5 and 15 minutes after injection.
g Using mirrors, or photographs captured either by the subject or another person with the subject’s imaging device (ie, cell phone, digital camera), or images
captured by the investigator or designee using the site’s digital photography system.
h Baseline Hexsel CSS Subsection D must be ‘0’ (absence of flaccidity or sagging skin) or ‘1’ (slightly draped appearance) on each buttock.
i Baseline CR-PCSS rating must be a ‘3’ (moderate) on each buttock.
j Based on live assessments while the subject is in front of the investigator.
k Compression garments will be worn after QWO (CCH-aaes) injection on Day 1 and worn 24 hours a day for the next 7 days.
l Apply instant cold packs immediately after QWO (CCH-aaes) injection for 5-10 minutes immediately after CCH-aaes injection while subject is in a prone
position.
m Arnica patches applied BID for 2 days immediately after QWO (CCH-aaes) injection on Day 1.
n Inhance Post-Injection Serum is applied QID directly on and around the injections site for up to 7 days after QWO (CCH-aaes) injection on Day 1, until
resolution of bruising.
o PDL treatment between Days 1 (same day of QWO [CCH-aaes] injection) and Day 7 after QWO (CCH-aaes) treatment. PDL settings are according to the investigator’s 
discretion.
p For the second and third QWO (CCH-aaes) treatment sessions, at the investigator’s discretion, subjects will be allowed to use the same mitigation treatment in
the same buttock (as applicable) that received mitigation treatment for the first CCH-aaes treatment session.
q AEs will be collected from the time the subject signed the ICF until end of the study or early termination.
BID = twice daily, d = Days, ET = early termination, ICF = informed consent form, QID = Four times daily


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2.1.
Inclusion Criteria
In order to be eligible to participate in the study, subjects must meet the following criteria at 
Screening and/or Day 1 visit:
1. Voluntarily sign and date an informed consent agreement.
2. Be a female ≥18 years of age and ≤ 50 years of age.
3. Have both buttocks with:
a.
A CR-PCSS score of 3 (moderate) as reported by the Investigator, and
b. A Hexsel CSS Subsection D “Grade of laxity, flaccidity, or sagging skin” score of 0 
(absence of laxity, flaccidity, or sagging skin) or 1 (slightly draped appearance).
4. Have a body mass index between ≥18 and ≤ 30 kg/m2, and intends to maintain stable 
body weight throughout the duration of the study (a variation of ≤ 10% from baseline 
body weight is permitted).
5. Have a Fitzpatrick skin rating of I-III.
6. Be willing to apply sunscreen before each exposure to the sun while participating in the 
study (ie, Baseline through end of study).
7. Be judged to be in good health, based upon the investigator’s medical judgment and the 
results of a medical history and physical examination at Screening. 
8. Be willing and able to cooperate with the requirements of the study.
9. Be able to read, complete and understand the patient reported outcomes rating 
instruments in English.
2.2.
Exclusion Criteria
A subject will be excluded from study participation if the subject:
1. Has any of the following systemic conditions:
a.
Coagulation disorder including but not limited to a Factor II, V, VII, or X deficiency.
b. Skin pigmentation disorder.
c.
Evidence or history of malignancy (other than excised basal-cell carcinoma) unless 
there has been no recurrence in at least 5 years.
d. History of keloidal scarring or abnormal wound healing.
e.
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, 
including but not limited to rheumatoid arthritis and/or other rheumatoid disease(s), 
Vitamin K deficiency, or liver diseases. Any questions about concurrent diseases 
should be discussed with the Medical Monitor.
f.
Evidence of clinically significant abnormalities on physical examination or vital 
signs.
2. Has any of the following local conditions in the buttocks:


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a.
History of lower extremity thrombosis or post-thrombosis syndrome.
b. Vascular disorder (eg, varicose veins, telangiectasia, vasculitis) in area to be treated.
c.
Inflammation or active infection in the buttocks.
d. Active cutaneous alteration including rash, eczema, or psoriasis.
e.
Has a tattoo in the buttocks, visible in clinical photographs.
3. Has skin laxity or linear undulations on either buttock that can be effaced by lifting skin.
4. Requires the following concomitant medications during the study and cannot discontinue 
these medications within the time specified before QWO (CCH-aaes) treatment:
a.
Antiplatelet medication (clopidogrel [Plavix®]) including aspirin at any dose within 
14 days of treatment.
b. Anticoagulants, such as warfarin (Coumadin®); heparin analogues within 14 days of 
treatment.
c.
Non-steroidal anti-inflammatory drugs (NSAIDS), such as ibuprofen (Motrin®, 
Advil®) and naproxen (Aleve®) 7 days before the study.
d. Any medications (eg, corticosteroids, certain antidepressants [eg, citalopram, 
fluoxetine], nutritional/homeopathic supplements [eg, fish oil, Vitamin E, omega 3, 
ginko biloba, ginger, St John’s Wart, green tea, ginseng, feverfew, saw palmetto, 
turmeric, bromelain]) or foods (eg, pineapple) that have, or have been reported to 
have anticoagulant effects within 14 days of treatment.
e.
Antibiotics, such as penicillin and cephalosporin within 48 hours of treatment.
5. Has used any of the following for the treatment of cellulite on a buttock within the 
timelines identified below or intends to use any of the following at any time during the 
study:
a.
Liposuction in a buttock during the 12-month period before injection of QWO (CCH-
aaes).
b. Injections (eg, mesotherapy, derma fillers, biostimulatory fillers); radiofrequency 
device treatments; laser treatment; buttock implant treatment; cryolipolysis; or 
surgery (including subcision and/or powered subcision) within a buttock during the 
12-month period before QWO (CCH-aaes) injection.
c.
Any investigational treatment for cellulite on the buttock during the 12-month period 
before the injection of QWO (CCH-aaes).
d. Endermologie™or similar treatments within a buttock during the 6-month period 
before injection of QWO (CCH-aaes).
e.
Massage therapy for cellulite within a buttock during the 3-month period before 
injection of QWO (CCH-aaes).
f.
Creams (eg, Celluvera™, TriLastin®) and/or home therapies to prevent or mitigate 
cellulite within a buttock during the 2-week period before QWO (CCH-aaes) 
injection.
6. Is presently nursing or providing breast milk or intends to do so during the study.
7. Intends to become pregnant during the study.


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8. Intends to initiate an intensive sport program regimen, exercise program regimen, or 
intensive weight reduction program during the study.
9. Has recently tanned or intends to use tanning spray or tanning booths during the study.
10. Intends to engage in strenuous activity within 48 hours after the first injection of QWO 
(CCH-aaes).
11. Has received an investigational drug or treatment within 30 days prior to injection of 
QWO (CCH-aaes).
12. Has a known systemic allergy to collagenase or any other excipient of QWO (CCH-aaes).
13. Has a known systemic allergy or local sensitivity to any of the mitigation treatments or 
included excipients (ie, arnica patches, INhance post-injection serum).
14. Has received any collagenase treatments at any time prior to treatment in this study.
15. Was a subject in a previous cellulite clinical trial of CCH: (EN3835, QWO [CCH-aaes]).
16. For subjects allocated to PDL treatment:
Subjects will be excluded from PDL treatment if they have any contraindications to PDL 
as indicated in the manufacturer’s documentation, for example but not limited to:
a. previous exposure to photosensitizing medications, food and/or supplements or other 
photosensitizing agents within 2 weeks of QWO (CCH-aaes) treatment.
b. exposure to Accutane® (isotretinoin) within 6 months of QWO (CCH-aaes) treatment.
2.3.
Selecting and Marking of Dimples
To ensure that the contralateral buttock that does not receive mitigation treatment can serve as 
the subject's own control, and that a similar level of injection site bruising will be induced, 
subjects should have a similar number of dimples requiring treatment. Subjects can be treated 
with up to 12 injections of QWO (CCH-aaes) on each buttock. The number of injections of 
QWO (CCH-aaes) administered to the right and left buttocks should be identical on Day 1. The 
number of injections may differ between treatment sessions, eg, 12 injections in each buttock in 
the first treatment session followed by fewer injections per buttock at the second and third 
treatment sessions as dimples improve.
For treatment, the investigator or qualified designee will select up to 12 dimples within each 
treatment area (each buttock) that are well-defined, evident when the subject is standing, and 
suitable for treatment.
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 1 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.


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2.4.
Treatment Administration
2.4.1.
QWO (CCH-aaes)
QWO will be provided by Endo Pharmaceuticals Inc.
Dosage and Mode of Administration: QWO (CCH-aaes), 0.84 mg, injected subcutaneously per 
buttock with both buttocks treated for a total dose of 1.68 mg. For each buttock, a dose of up to 
0.84 mg of QWO (CCH-aaes) in 3.6 mL will be administered as up to 12 subcutaneous injections 
(0.3-mL injection administered as three 0.1-mL aliquots per injection). There will be 3 treatment 
visits at intervals of approximately 21 days as described in schedule of assessments.
To induce a similar extent and severity of bruising in each buttock, approximately the same 
number of injections should be administered to the left and to the right buttock. However, the 
number of injections per buttock may differ among treatments. The number of injections 
administered to each buttock on Day 1 must be recorded. The volume and dose of injection at 
each treatment visit will be injected per the QWO Prescribing Information. QWO will be 
provided in cartons containing 1 QWO 1.84-mg single-dose vial and 1 diluent for QWO 8-mL 
single-dose vial.
2.4.2.
Mitigation Treatments
Mitigation treatments will be provided locally by each investigator/subject.  
At the investigator’s discretion and with consent of the subject, mitigation treatments provided 
after the first treatment session of QWO (CCH-aaes), can be administered after the second and 
third QWO (CCH-aaes) treatment sessions. Mitigation treatments administered after each
treatment session with QWO (CCH-aaes) may be recorded as concomitant medications.
Cohort 1 will serve as a control and no mitigation treatment will be administered.
2.4.2.1.
Compression Garments (Cohort 2)
Subjects will be instructed to wear a commercially available compression garment (ie, SPANX 
Grade 3) after the injection on Day 1, for 24 hours per day for 7 days after the injection (Day 1 –
Day 8). Garments may be removed for personal hygiene and when the subject is being evaluated 
at the investigator’s office during study visits. Subjects should be informed that ill-fitting 
compression garments may contribute to pain.
2.4.2.2.
Instant cold packs (Cohort 3)
Instant cold packs should be applied to the right buttock only for 5-10 minutes immediately 
after the injection of QWO (CCH-aaes) while the subject is lying in prone position.
2.4.2.3.
Arnica Gel Patches (OcuMend) (Cohort 4)
Subjects will be instructed to apply OcuMend gel patches (arnica montana 50% and ledum 
palustre) immediately after the CCH-aaes injection to the right buttock only BID on Days 1 
and 2 for a total of 4 doses. One or two patches per application may be required depending on 
the extent of the bruising.


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2.4.2.4.
INhance Post-Injection Serum with TriHex Technology (Cohort 5)
INhance Post-injection Serum will be applied by investigators at the site of injections on Day 1 
on the right buttock only and then by the subject or subject’s associate QID for up to 7 days 
after injection or until resolution of bruising according to the product instructions. The serum is 
available in a small 10-mL tube with a chilled tip. A small amount of the serum will be applied 
on the skin and around the injection site and gently rubbed in using the cooling applicator.
2.4.2.5.
Pulse Dye Laser Treatment (Cohort 6)
Investigators will apply laser treatment with PDL to the bruising observed on the right 
buttock only as a single treatment between Day 1 (same day of QWO [CCH-aaes) injection) 
and Day 7 after QWO (CCH-aaes) treatment.
The investigator can adjust laser settings at his/her discretion. Laser settings will be recorded in 
detail to allow comparability across sites. Only select sites will be administering laser treatment.
2.5.
Measures to Minimize Bias
This is an open label study, however, the mitigation treatment for each subject will be assigned 
in a 1:1:1:1:1:1 ratio using a Mitigation Treatment Assignment Table. To ensure a balanced 
approach in the application of mitigation treatments and the assessment of bruising among the 
sites and investigators, 1-3 subjects per site will be assigned to each mitigation treatment 
(pending site capabilities, subjects available, and available mitigation equipment).
At Screening, the investigator or designee will refer to the Mitigation Treatment Assignment 
Table to determine which mitigation treatment should be administered.
The investigator must maintain a subject master log linking the subject identification number to 
the subject’s name. The subject identification number will not be reassigned to another subject in 
this study in the case of study withdrawal.
2.6.
Digital Photographs
At the time points indicated on the schedule of assessments, the investigator or qualified 
designee will photograph bilateral buttocks in a single photograph while the subjects is 
standing in a consistent, standard relaxed pose, with relaxed gluteus muscles using the 
investigator’s digital camera. Photographs of bilateral buttocks will be obtained:

Before and after marking dimples and injection sites (prior to injections) on 
Days 1, 22, and 43.

During the Days 2, 4, 7, 14, and 71 visits (end of study/ET) (no dimple or 
injection site markings).
2.7.
Investigator Assessment Ratings
2.7.1.
Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS)
Investigators will rate the severity of the cellulite of each buttock, independently, at the 
Screening visit using the 5-level Clinician-Reported Photonumeric Cellulite Severity Scale 
(CR-PCSS). 


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The following labels and descriptions are associated with each level of severity on the CR-PCSS 
Buttock scale (Table 3): 
Table 3: 
Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS)
Rating
Response Option
0
None: No dimples or evident cellulite
1
Almost None: Few dimples that are mostly superficial in depth
2
Mild: Several dimples of which most are shallow in depth
3
Moderate: Many dimples of which most are moderate in depth
4
Severe: A lot of dimples with some of more severe depth
Investigators will be instructed to look at each buttock under evaluation ‘live’ with the subject 
standing in front of him/her with relaxed gluteus muscles. Investigators who are physicians will 
be trained and qualified on the use of the CR-PCSS prior to assessing any subjects.  
Subjects must have a baseline CR-PCSS rating of ‘3’ (moderate) on each buttock at the 
Screening visit to be included in the study.
2.7.2.
Hexsel Cellulite Severity Scale (CSS)
The Hexsel CSS is a photonumeric scale that looks at 5 key morphologic features of cellulite[3,4]:

A - Number of evident depressions.

B - Depth of depressions.

C - Morphological appearance of skin surface alterations.

D - Laxity, flaccidity or sagging of skin.

E - Current classification scale based on medical literature.
Each of these features is evaluated on a 4-point scale from a low of 0 to a high of 3. For this 
study, only “D - laxity, flaccidity or sagging of skin” will be assessed for eligibility.
Investigators who are physicians will use the Hexsel CSS Subsection D (laxity, flaccidity or 
sagging of skin) to assess the severity of laxity in each buttock at the Screening Visit (Table 4). 
The assessment will be made while the subject is in the standing position with relaxed gluteus 
muscles.  
Table 4: 
Hexsel CSS (D) laxity, flaccidity or sagging of skin
Rating
Description
0
Absence
1
Slight
2
Moderate 
3
Severe
To participate in the study, for each buttock, subjects must have a Baseline Hexsel CSS 
Subsection D rating of ‘0’ (absence of flaccidity or sagging skin) or ‘1’ (slightly draped 
appearance) at the Screening Visit.


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2.7.3.
Investigator Assessment of Bruising Severity Scale
Severity of bruising for each buttock will be documented on the Investigator Assessment of 
Bruising Severity Scale on Days 1, 2, 4, 7, 14, and 22 (before injection). Investigators will be 
asked to rate the level of subject bruising using a 5-point photonumeric scale (Table 5):
Table 5: 
Investigator Bruising Severity Scale
Rating
Response Option
0
None or almost no bruising
1
Mild Bruising
2
Moderate Bruising
3
Severe Bruising
4
Very Severe Bruising
Investigators will document their responses on the corresponding page of the eCRF.
2.7.4.
Investigator Bruising Improvement Scale (I-BIS)
On Days 2, 4, 7, 14, and 22 (before injection), the investigator will rate the bruising of the 
mitigation-treated buttock when compared to the untreated (with mitigation treatment) buttock 
using the 3-point Likert scale (Table 6). Scores on the higher end of the range indicate greater 
improvement of bruising with treatment. 
Table 6:
Investigator Bruising Improvement Scale (I-BIS)
Rating
Response Option
1
Worse (more bruising)
2
Similar
3
Improved (less bruising)
The I-BIS evaluations will be based on live assessments while the subject is in front of the 
investigator. Note that the I-BIS assessment cannot be completed for subjects that either do not 
receive mitigation treatment (Cohort 1) or subjects that receive bilateral mitigation treatment (as 
in Cohort 2), as there is no untreated buttock for comparison.
2.7.5.
Investigator-Global Aesthetic Improvement Scale (I-GAIS)
On Days 22, 43, and 71, the investigator will determine the degree of improvement of each of the 
buttocks by comparing the cellulite by live assessment on Days 22, 43, and 71 to the Day 1 
pre-treatment (Baseline) image of that buttock (Table 7). The investigator will provide a separate 
rating for each buttock from the I-GAIS and enter the results on the corresponding page of the 
eCRF.


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Table 7: 
Investigator Global Aesthetic Improvement Scale (I-GAIS)
Rating
Response Option
Description
+3
Very much improved
Optimal cosmetic result from treatment of the treated dimples
+2
Much improved
Marked improvement in the treated area appearance from before 
treatment, but not completely optimal
+1
Improved
Obvious improvement in the treated area appearance from before 
treatment, but additional treatment is indicated
0
No change
The treated area appearance is essentially the same as before treatment
−1
Worse
The treated area appearance is worse than before treatment
−2
Much worse
Marked worsening in appearance from the initial condition
−3
Very much worse
Obvious worsening in appearance from the initial condition
2.8.
Subject Assessment Ratings
2.8.1.
 
 
2.8.2.
Subject Bruising Improvement Scale (S-BIS)
On Days 2, 4, 7, 14, and 22 (before injection), the subject will rate the bruising of the mitigation-
treated buttock when compared to the untreated (with mitigation treatment) buttock using the 
3-point Likert scale (Table 8). Scores on the higher end of the range indicate greater 
improvement of bruising with treatment.
Table 8: 
Subject Bruising Improvement Scale (S-BIS)
Rating
Response Option
1
Worse (more bruising)
2
Similar
3
Improved (less bruising)
Note that the S-BIS assessment cannot be completed for subjects that either do not receive 
mitigation treatment (Cohort 1) or subjects that receive bilateral mitigation treatment (as in 
Cohort 2), as there is no untreated buttock for comparison.
2.8.3.
Patient Bother by Bruising Scale
On Days 4, 7, and 22 (before injection), subjects will indicate their level of bother by bruising for 
each buttock using a 4-point scale.  Subjects were asked “Thinking about the bruising on your 


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left/right buttock, how bothered are you with the appearance of the bruising on your left/right 
buttock?” and asked to respond using one of the following ratings (Table 9):
Table 9: 
Patient Bother by Bruising Scale
Rating
Description
1
Not at all bothered
2
A little bothered
3
Moderately bothered
4
Extremely bothered
Subjects may use a mirror, or photographs captured by the subject or another person with the 
subject’s imaging device (ie cell phone, digital cameras) or images captured by the investigator 
or designee using the site’s digital photography system. 
2.9.
Skin Assessment (Fitzpatrick Scale)
At the Screening Visit, subject skin type will be evaluated by the Investigator using the 
Fitzpatrick Scale (Table 10).  Only subjects with a Fitzpatrick skin rating of I-III at the Screening 
Visit will be included in the study.
Table 10: 
Fitzpatrick Scale
Rating
Response Option
Description
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
2.10.
Weight, Height, and BMI
At the Screening Visit, height and weight measurements will be taken. Baseline body mass index 
(BMI) will be computed from these measurements as the weight in kilograms (kg) divided by 
height in meters squared (m2). 
Body weight will also be measured at the Day 71/ET visit; BMI will be computed from this 
measurement using the height at Screening.
2.11.
Adverse Events
Adverse Events (AEs), including both observed or volunteered problems, complaints, signs or 
symptoms must be recorded, regardless of whether associated with the use of study treatment. 
Study treatment includes QWO (CCH-aaes) and mitigation treatments. 
The following information will be collected for all AEs: 

Verbatim description 

Injection Site Reaction (Yes/No)

Date of Onset


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
Date of Resolution/or Ongoing

Severity (Mild, Moderate, Severe)

Relationship to QWO (CCH-aaes) (Not Related, Unlikely Related, Possibly Related, 
Probably Related) 

Action taken with QWO (CCH-aaes) (None, Interrupted, Withdrawn)

Relationship to Mitigation Treatment (Not Related, Unlikely Related, Possibly 
Related, Probably Related) 

Action taken with Mitigation Treatment (None, Interrupted, Withdrawn)

Outcome (Recovered/Resolved, Recovered/Resolved w/Sequelae, Recovering/ 
Resolving, Not Recovered/Not Resolved, Fatal, Unknown)

Whether or not a concomitant medication or procedure was required

Classified as a serious adverse event (SAE) or not

SAE Code (Death, Life-threatening, Inpatient or prolonged hospitalization, Persistent 
or significant disability/incapacity, Congenital anomaly or birth defect, Other 
medically important event)
2.12.
Medical History
Medical history and cellulite history, including all prior procedures to treat cellulite, will be 
obtained at the Screening Visit.  Medical history will include a review of the following systems: 
general, dermatological, respiratory, cardiovascular, gastrointestinal, genitourinary, 
gynecological, endocrine, musculoskeletal, hematological, neuropsychological, immune 
(allergies), and head, eyes, ears, nose, and throat. Historical and current medical conditions 
including date of last menstrual period will be recorded.
History of tobacco and alcohol use (never, current, former) will also be collected.
Surgical history will include a review of all surgical procedures completed in the prior 5 years 
and any surgery completed at any time in the treatment area.
2.13.
Physical Examination
A limited physical examination will include evaluation of height, weight, lungs, heart, abdomen, 
and extremities will be conducted at the Screening Visit. Weight will also be recorded at the Day 
71/ET visit.
2.14.
Vital Signs
Temperature, pulse, systolic blood pressure, and diastolic blood pressures will be collected at 
the Screening Visit, and before the first QWO (CCH-aaes) injection and approximately 
30 minutes after injection on Day 1. Pulse and blood pressure will be collected after the subject 
has been sitting for 5 minutes.


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The investigator will review all vital sign values for clinical significance. Any vital sign value 
meeting the investigator’s criteria for clinical significance will be recorded as an AE (or SAE, if 
appropriate).
2.15.
Pregnancy 
All pregnancies in subjects identified during or after this study, where the estimated date of 
conception is determined to have occurred during the study or within 28 days of the last study 
treatment in subjects who terminate the study early, must be reported, followed to conclusion, 
and the outcome reported, even if the subject is discontinued from the study. 
Subjects will be instructed to immediately notify the investigator of any pregnancies.
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, including spontaneous miscarriages, must additionally be reported 
and handled as SAEs.
A subject who becomes pregnant must be withdrawn from the study. 
2.16.
Prior and Concomitant Medications and Procedures
Any prior medications and nondrug therapies (eg, blood transfusions, oxygen supplementation, 
physical therapy, etc.), including all prior medications and/or procedures for cellulite, taken 
within the 30 days prior to the Baseline Visit will be recorded. Any concomitant medications 
and/or nondrug therapies received from the Baseline Visit through the Day 71 Visit will also be 
recorded. Mitigation treatments administered after each treatment session of QWO (CCH-aaes) 
may be recorded as concomitant medications or procedures, as appropriate.
2.16.1.
Prohibited Medications
During the study, the following treatments are prohibited:

Anticoagulants (ie, warfarin [Coumadin] heparin analogues)

Antiplatelet medications (eg, clopidogrel [Plavix], aspirin)
2.16.2.
Suggested Concomitant Medications and Procedures
During the study, acetaminophen will be permitted to treat pain at the injection site as needed.  
Other required concomitant medications may be administered at the investigator’s discretion.
2.17.
COVID-19 Related Protocol Deviations
All study assessments conducted outside of the allowed windows outlined in the schedule of 
assessments due to a COVID-19 interruption will be documented as a protocol deviation. 
COVID-19 will be recorded as the reason for these out-of-window assessments.


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3.
STUDY PARAMETERS
3.1.
Subject Disposition
Subjects will be considered as completing the study if they complete the Day 71 visit. Subjects 
who do not complete the study will report their reason for early discontinuation. 
Time in the study (days) will be computed as the date of last visit minus the date of Day 1 + 1, 
where the date of the last visit is determined as the following:

The date of Day 71 if the subject completes the study

The date of early termination visit if the subject is terminated early from study at a 
non-scheduled visit

The date of the latest scheduled visit if the subject is terminated early from study at a 
scheduled visit or lost to follow-up
3.2.
Early Termination Visit Assessments
Subjects who discontinue study treatment (QWO [CCH-aaes] or mitigation treatment) or are 
withdrawn from the study will be encouraged to complete the remaining study visits and 
evaluations, including providing any additional follow-up information, unless the subject 
specifically indicates that they will not participate in any further evaluations.
Subjects who discontinue or are withdrawn from the study at any time after the first dose of the 
study treatment (QWO [CCH-aaes] and mitigation treatments) will not be replaced.
Permanent study discontinuation is required if the subject becomes pregnant during the study.
3.3.
Study Treatment 
Subjects will be divided into 1 of 6 treatment cohorts (different mitigation treatments along with 
the same QWO treatment). Subjects will first receive up to 0.84 mg of QWO (CCH-aaes) 
injected subcutaneously per buttock with both buttocks treated. There will be 3 treatment visits at 
intervals of 21 days as described in the schedule of assessments. Mitigation treatments will be 
provided locally by each investigator/subject, and can be administered after each treatment 
session of QWO (CCH-aaes).  
3.3.1.
QWO (CCH-aaes) Assessments
To induce a similar extent and severity of bruising in each buttock, approximately the same 
number of injections (up to 12 per buttock) will be administered to the left and right buttock; 
however, the number of injections per buttock may differ among treatments as dimples improve.  
The number of injections administered at each treatment session will be recorded for each 
buttock. The difference in the number of injections administered will be computed for each 
subject for each QWO treatment session as (number of QWO injections in left buttock) –
(number of QWO injections in right buttock). A positive difference is indicative of more 
injections in the left buttock, while a negative difference is indicative of more injections in the 
right buttock.


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3.3.2.
Mitigation Assessments
Mitigation treatments administered after each treatment session of QWO (CCH-aaes) will be 
recorded on the Study Mitigation Treatment page of the eCRF. The start and stop date, type of 
mitigation treatment, and location (left and/or right buttock) will be recorded and assessed.  
Mitigation treatments may also be recorded as concomitant medications or procedures; these 
treatment records will be included in corresponding assessments (see section 3.6.2).
3.3.3.
Cohorts
The cohorts will be structured as described in Table 1, and will be summarized by the mitigation 
treatment used:

Cohort 1: No mitigation treatment (control)

Cohort 2: Compression garments

Cohort 3: Instant cold packs

Cohort 4: Arnica gel patches (OcuMend)

Cohort 5: INhance post-injection serum with TriHex technology

Cohort 6: Pulse Dye Laser (PDL) treatment
Once subjects are assigned to a particular cohort using the site-specific Mitigation Treatment 
Assignment Table, the cohort assignments will remain regardless of the actual treatment 
received. Subjects who receive a different mitigation treatment at any time from the mitigation 
treatment to which they were assigned will be reported as a protocol deviation. 
3.4.
Efficacy Parameters
3.4.1.
Investigator Bruising Severity Scale 
3.4.1.1.
Investigator Bruising Severity Scale Rating
The Investigator Bruising Severity Scale Rating is directly obtained from the investigator’s 
assessments of each buttock at an evaluation visit. 
3.4.1.2.
Baseline Investigator Bruising Severity Scale Rating
The Baseline Investigator Bruising Severity Scale Rating is the rating obtained for this item from 
the investigator’s assessments on Day 1.
3.4.1.3.
Change from Baseline Investigator Bruising Severity Scale Rating
The change from baseline Investigator Bruising Severity Scale Rating will be the visit rating 
minus the baseline rating. A negative change in score indicates a reduction in subject bruising 
severity, while a positive change in score indicates an increase in subject bruising severity.


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3.4.2.
I-GAIS
3.4.2.1.
I-GAIS Rating
The I-GAIS rating is directly obtained from the investigator’s assessments of each buttock at an 
evaluation visit. 
3.4.2.2.
One-Level I-GAIS Responder 
One-level I-GAIS Responder is defined as any subject with an improved (+1, +2 or +3) score on 
the I-GAIS at an evaluation visit.
3.4.3.
I-BIS Rating
The I-BIS rating is directly obtained from the investigator’s assessment rating comparing the 
bruising of the mitigation-treated buttock to the untreated (with mitigation treatment) buttock at 
an evaluation visit. Note that this assessment cannot be completed in either subjects that do not 
receive mitigation treatment (Cohort 1) or subjects that receive bilateral mitigation treatment (eg, 
Cohort 2 – compression garments) since the subjects in those two cohorts do not have a untreated 
buttock as a comparator.
3.4.4.
S-BIS Rating
The S-BIS rating is directly obtained from the subject’s assessment rating comparing the 
bruising of the mitigation-treated buttock to the untreated (with mitigation treatment) buttock.  
Note that this assessment cannot be completed in either subjects that do not receive mitigation 
treatment (Cohort 1) or subjects that receive bilateral mitigation treatment (eg, Cohort 2 –
compression garments) since the subjects in those two cohorts do not have a untreated buttock as 
a comparator.
3.4.5.
Patient Bothered by Bruising Scale Rating
The Patient Bothered by Bruising Scale rating is directly obtained from the subject’s answer to 
the question “how bothered are you with the appearance of the bruising on your left/right 
buttock?” for each buttock. To complete this assessment, subjects may use either a mirror or 
photographs captured by the subject or another person with the subject’s imaging device, or 
images captured by the investigator or designee using the site’s digital photography system.
  
 
 


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3.5.
Safety Parameters
3.5.1.
Adverse Events and Treatment-Emergent Adverse Events
Adverse events will be mapped to system organ class and preferred term using the Medical 
Dictionary for Regulatory Activities (MedDRA). Treatment-emergent adverse events (TEAEs) 
are any AEs with a start date equal to or after the date of the first injection of QWO (CCH-aaes). 
3.5.1.1.
Adverse Event Duration
Duration of an AE will be the AE end date minus the AE start date + 1. If AEs are still ongoing 
at the end of the study or AEs have partial start or stop dates, durations of those AEs are not 
determined.
3.5.1.2.
Intensity of Adverse Events
Intensity (or severity) of AEs will be graded as “mild”, “moderate” or “severe”. For AEs with 
missing severity, the most severe assessment will be imputed for analyses, following worst-case 
principle. If the intensity of an AE changes, then the most severe intensity during the continuous 
episode will be recorded.
3.5.1.3.
Relationship to QWO (CCH-aaes) 
The causal relationship with study drug (QWO [CCH-aaes]) will be classified by the investigator 
and will be reported as follows:

Not related.

Unlikely related.

Possibly related.

Probably related.
QWO-related adverse events are AEs with the relationship described by the investigator as 
“probably related” or “possibly related”. “Not related” or “unlikely related” causality 
assessments are considered as not related.
Any missing relationship of an AE to QWO (CCH-aaes) will be considered as related for the 
analyses, following worst-case principle. 
3.5.1.4.
Relationship to Mitigation Treatment 
The causal relationship with mitigation treatment will be classified by the investigator and will 
be reported as follows:

Not related.


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
Unlikely related.

Possibly related.

Probably related.
Mitigation-related adverse events are AEs with the relationship described by the investigator as 
“probably related” or “possibly related”. “Not related” or “unlikely related” causality 
assessments are considered as not related.
Any missing relationship of an AE to mitigation treatment will be considered as related for the 
analyses, following worst-case principle. 
3.5.1.5.
Action Taken with QWO (CCH-aaes) and Mitigation Treatments
The action taken with QWO (CCH-aaes) treatment and/or the mitigation treatment will be 
reported by the investigator as follows:

Not changed

Interrupted.

Withdrawn.
Actions taken with QWO (CCH-aaes) will be reported separately from actions taken with 
mitigation treatment. 
3.5.2.
Vital Signs 
The baseline values for vital signs (study baseline) will be those taken at Day 1 pre-dose for the 
by-visit analyses.
Vital signs will be analyzed for Day 1, with pre-dose value as baseline and post-baseline 
measurement taken approximately 30 minutes after injection. Change from baseline will be the 
post-baseline value minus the baseline value.
3.6.
Other Parameters
3.6.1.
Medical History
Medical history will be mapped to preferred term using MedDRA. All medical history terms will 
be reviewed by the study medical monitor to determine if any other terms should be included.
3.6.2.
Prior/Concomitant Medications and Procedures
A concomitant medication is any medication with a stop date on or after the date of the first 
QWO (CCH-aaes) injection, or a medication reported as ongoing. A prior medication is any 
medication taken prior to the date of the first QWO (CCH-aaes) injection. All medications will 
be coded with the World Health Organization (WHO) drug dictionary, by active ingredient and 
WHO anatomical therapeutic chemical (ATC) classification of ingredients. 


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A concomitant procedure is any procedure and/or nondrug therapy with a stop date on or after 
the date of the first QWO (CCH-aaes) injection, or a procedure and/or nondrug therapy reported 
as ongoing.  A prior procedure is any procedure and/or nondrug therapy administered prior to the 
date of the first QWO (CCH-aaes) injection. Procedures will be reported using the “Additional 
Concomitant Procedure/Therapy” page of the eCRF. 
For all previous and concomitant medications, the following information will be collected: 
medication name, start date, stop date or ongoing, dose and dose unit, route of administration, 
frequency, indication, and whether the medication is used to treat an adverse event (Yes/No).
For all previous and concomitant procedures, the following information will be collected:  
description of procedure/surgery/non-drug therapy, start date, stop date or ongoing, indication, 
and whether the therapy/procedure is used to treat an adverse event (Yes/No).
4.
ANALYSIS POPULATIONS
4.1.
Safety Population
The Safety Population is defined as all subjects allocated to treatment who receive at least 
1 injection of QWO (CCH-aaes) with or without mitigation treatment. All demographic and 
baseline characteristics, as well as safety parameters, will be summarized based on this 
population. 
4.2.
Evaluable Population
The Evaluable Population is defined as all subjects allocated to treatment who receive at least 
1 injection of QWO (CCH-aaes) and have at least 1 bruising assessment after the first dose of 
QWO (CCH-aaes). The primary and key secondary efficacy parameters will be summarized 
based on this population. 
5.
STATISTICAL METHODS
5.1.
Overview
The primary efficacy endpoint will be summarized as frequency counts and percentages based on 
the Evaluable Population by cohort. Mean and standard deviation (SD) will also be provided.
The secondary and supportive efficacy endpoints except for change from baseline measures will 
be summarized as frequency counts and percentages based on the Evaluable Population by 
cohort and by buttock, where appropriate. The change from baseline measures will be 
summarized using descriptive statistics (n, mean, SD, median, minimum and maximum). 
TEAEs will be summarized as frequency counts and percentages by preferred term and by 
cohort. The results and change from baseline for vital signs will be summarized using descriptive 
statistics.
Subject listings of all data from the eCRFs as well as any derived variables will be presented.


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5.2.
Missing Data Handling
Missing efficacy data will not be imputed for analysis unless otherwise specified.  
5.3.
Subject Disposition
The number of subjects included in each study population will be summarized by cohort and 
overall. Subjects excluded from the Safety Population or Evaluable Population will be listed.
The number and percentages of subjects screened, enrolled, completed, and withdrawn from the 
study, as well as the reason for withdrawal from study will be summarized by cohort and overall. 
The number and percentage of screen failures will also be shown.
A listing of disposition data will be provided. Screen failure reasons will also be listed. In 
addition, a listing for inclusion/exclusion criteria will also be presented.
5.4.
Protocol Deviations
Protocol deviations will be divided in categories and severity (major/minor) will be determined. 
Protocol deviations will not be summarized; however, a subject listing will be presented. 
5.5.
Demographics and Baseline Characteristics
Demographics and baseline characteristics will be summarized by cohort and overall using the 
Safety Population. Age, height (at Screening), body weight (at Screening), and BMI in kg/m2 (at 
Screening) will be summarized as continuous variables using descriptive statistics (n, mean, 
standard deviation (SD), median, minimum and maximum). 
Gender, race and ethnicity will be summarized as categorical variables using frequency counts 
and percentages. In addition, age group and BMI group will be summarized as categorical 
variables using frequency counts and percentages.
The following baseline characteristics will be summarized using frequency counts and 
percentages:

CR-PCSS cellulite severity ratings for each buttock at Screening.

Hexsel CSS Section D (laxity, flaccidity or sagging of skin) scores for each buttock at 
Screening.

Skin category based on Fitzpatrick Skin Scale assessment.

Report of tobacco and alcohol use

Alcohol use (Never, Current, and Former).

Tobacco use (Never, Current, and Former).
All demographic and baseline characteristics will be presented in subject listings.


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5.6.
Medical and Surgical History
Medical and surgical history, including cellulite history and previous treatments, will be coded 
using MedDRA. Medical and surgical history data will not be summarized; however, a subject 
listing will be provided.
5.7.
Efficacy Evaluation
Efficacy parameters will be summarized for each mitigation group based on the Evaluable 
Population, unless otherwise stated. Missing values will not be imputed, and only observed data 
will be summarized.
For mitigation treatments that are bilaterally administered (e.g. compression garments in cohort 
2), efficacy parameters will be compared to the control arm (cohort 1).  For mitigation treatments 
that are unilaterally applied (e.g. instant cold packs, arnica patches, INhance, and PDL treatment 
in cohorts 3-6, which are applied to the right buttock only), subjects will serve as their own 
control. In these cases, efficacy parameters from mitigation treatment (right buttock) will be 
compared to contralateral buttock with no mitigation treatment (left buttock).  There will be no 
formal comparison of efficacy parameters between mitigation treatments.
5.7.1.
Overview of Treatment 
Summaries for both QWO (CCH-aaes) and mitigation treatments will be provided for the Safety 
Population.  
5.7.1.1.
QWO (CCH-aaes)
The following information regarding QWO (CCH-aaes) treatment will be summarized for each 
buttock by cohort:

Number of QWO (CCH-aaes) treatment sessions per subject

Number of subjects who received QWO (CCH-aaes) treatment or did not receive 
QWO (CCH-aaes) treatment each treatment visit

For subjects who had the QWO (CCH-aaes) treatment done, the number of injections 
given at each treatment visit

For subjects who had the QWO (CCH-aaes) treatment done, the subject-level 
difference in the number of injections given at each treatment visit (left buttock –
right buttock).
A subject listing containing all QWO (CCH-aaes) treatment administration information will be 
provided.
5.7.1.2.
Mitigation
The following information regarding mitigation treatments will be summarized for the treated 
buttock(s), by cohort:

Number of mitigation treatment sessions per subject per QWO treatment cycle


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
For subjects who had mitigation treatment done, the type of mitigation treatment 
received, by treatment visit
Note that for Cohort 2, mitigation treatment was administered to both left and right buttocks.  For 
Cohorts 3-6, mitigation treatment was administered to right buttock only.  Cohort 1 did not 
receive mitigation treatment and therefore will not be included in mitigation treatment 
summaries.
A subject listing containing mitigation treatment administration information will be provided.  
5.7.2.
Primary Endpoint and Secondary Endpoints – Bruising Level
For each cohort, results at each level of bruising on the Investigator Assessment of Bruising 
Severity Scale (see section 2.7.1) will be summarized by visit and by buttock for each subject
using counts and percentages. Results and changes from baseline evaluation rating will also be 
summarized using descriptive statistics (mean and SD).
A listing of Investigator Assessment of Bruising Severity ratings will be provided.
5.7.3.
Secondary Endpoints – Improvement of Bruising
For each cohort, results at each rating level of the I-GAIS (see section 2.7.5) will be summarized 
by visit and by buttock for each subject using counts and percentages, along with mean and SD.  
Additionally, the 1-level I-GAIS responders (as defined in section 3.4.2.2) will be summarized 
by cohort and by buttock for each subject using counts and percentages of subjects.  A listing of 
I-GAIS ratings will be provided.
For subjects that receive unilateral mitigation treatments (cohorts 3-6), results at each rating level 
of the I-BIS (see section 2.7.4) will also be summarized by visit using counts and percentages.   
A listing of I-BIS ratings will be provided.
For subjects that receive unilateral mitigation treatments (cohorts 3-6), results at each rating level 
of the S-BIS (see section 2.8.2), as determined by the subject’s self-assessment, will be 
summarized by visit using counts and percentages. A listing of S-BIS ratings will be provided. 
5.7.4.
Secondary Endpoints – Patient Bothered by Bruising
For each cohort, results at each rating level of the Patient Bother by Bruising Scale (see section 
2.8.3) will be summarized by visit and by buttock for each subject using counts and percentages.  
A listing of Patient Bother by Bruising ratings will be provided. 
5.7.5.
Exploratory Endpoints –
 
 
 
 
 


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5.8.
Safety Evaluation
5.8.1.
Adverse Events
The following listings will be provided based on all AEs:

Listing of deaths.

Listing of non-fatal SAEs.

Listing of non-serious AEs leading to discontinuation from study.
Listing of non-serious AEs leading to interruption or discontinuation of either QWO (CCH-aaes) 
or mitigation treatment. The following summary tables of AEs will be presented by cohort:

TEAEs

Overall summary

By preferred term  

By preferred term and severity

By frequency of SAEs

By frequency of most common non-SAE

QWO-related AEs 

Overall summary

By preferred term 

By preferred term and severity

Mitigation-related AEs 

Overall summary

By preferred term 

By preferred term and severity
The overall summary will consist of the following items: 

Total number of AEs

All AEs

Mild AEs

Moderate AEs

Severe AEs

Related to QWO (CCH-aaes) Only (TEAEs overall summary only)

Related to Mitigation Only (TEAEs overall summary only)

Related to both QWO (CCH-aaes) and Mitigation (TEAEs overall summary only)

Total number of subjects with

At least 1 AE


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
At least 1 SAE 

At least 1 severe AE 

No severe AEs but at least 1 moderate AE

No severe/moderate AEs but at least 1 mild AE

At least 1 AE leading to discontinuation from study

At least 1 AE leading to interruption or discontinuation of QWO (CCH-aaes) only 
(TEAE overall summary only)

At least 1 AE leading to interruption or discontinuation of Mitigation Treatment 
only (TEAE overall summary only)

At least 1 AE leading to interruption or discontinuation of both QWO (CCH-aaes) 
and Mitigation Treatment (TEAE overall summary only)

Total number of subjects who died (TEAEs overall summary only)
Percentages for the total number of mild, moderate, and severe AEs will be based on the total 
number of all AEs in the cohort.
The by frequency summaries will also include the total number of occurrences the AE preferred 
term was reported as well the number of subjects with at least 1 report of the AE.  Most common 
non-SAEs are any preferred term AE that at least 5% of the subjects in any cohort report at least 
once. 
5.8.1.1.
Adverse Event Conventions
The following conventions will be followed:

Table by preferred term - If an AE preferred term occurred multiple times within a 
body system for the same subject, the preferred term will only be counted once for the 
subject for the summary of preferred terms. If an AE body system occurred multiple 
times for the same subject, the body system will only be counted once for the subject 
for the summary of body systems. If a subject has any AE, the subject will be counted 
once in the summary of subjects with at least 1 AE.

Table by preferred term and severity - If an AE preferred term occurred multiple 
times within a body system for the same subject, only the most severe one will be 
used. If the most severe preferred term of an AE occurred multiple times within a 
body system for the same subject, only 1 will be counted. In addition, this summary 
will also contain the total number of subjects with at least 1 mild, 1 moderate, or 
1 severe. If a subject has at least 1 severe AE, then the subject will be counted in the 
severe category. If the subject has no severe AEs, but at least 1 moderate AE, then the 
subject will be counted in the moderate category, and if the subject has no severe and 
no moderate AEs, but has at least 1 mild AE, then the subject will be counted in the 
mild category.

Table of frequency of preferred terms – Preferred terms will be ordered by their 
descending frequency within the treatment cohort. If 2 or more preferred terms are 
tied in their frequency, then the preferred terms will be ordered alphabetically.


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5.8.2.
Weight and BMI
Weight and BMI at baseline, Day 71/ET, and change from baseline will be summarized by 
treatment cohort. 
5.8.3.
Vital Signs
Vital signs on injection day will be summarized at baseline (pre-injection) and post-injection 
time points (30 minutes after injection) and change from baseline by treatment cohort. The 
baseline value will be based on the pre-injection measurement at each treatment session. A 
listing of all vital sign information will be provided.
5.8.4.
Prior and Concomitant Medications and Procedures
Prior and concomitant medications will be summarized by cohort and overall using frequency 
counts and percentages by active ingredient within each ATC, with ATC and active ingredients 
ordered alphabetically. Prior and concomitant procedures (nondrug therapies) will be 
summarized by cohort and overall using frequency counts and percentages with name of the 
procedures ordered alphabetically. Multiple uses of the same medication/procedure by a subject 
will be counted only once. 
Subject listings of medications (indicating prior and concomitant medications) and procedures 
(indicating prior and concomitant procedures) will be provided. 
Mitigation treatments recorded as concomitant medications or concomitant procedures will be 
included in associated summaries and listings.
6.
DERIVED VARIABLES
6.1.
Subject Level Variables
The following variables will be determined for each subject (see Table 11).
Table 11: 
Subject Level Derived Dataset Variables
Variable
Definition
Age Group
 18 – <25 years
25 – <35 years
  35 – 50 years
Height (cm)
If height unit is inches, then height is equal to the recorded value multiplied by 
2.54 and then rounded to 1 decimal point.
Weight (kg)
If weight unit is pounds, then weight is equal to the recorded value multiplied 
by 0.454 and then rounded to 1 decimal point.
BMI (kg/m2)
Weight/(Height/100)2
BMI Group
Normal Weight (<25.0 kg/m2)
Overweight (≥25.0 kg/m2)
Baseline
For Investigator Assessment of Bruising Severity Scale: Day 1 measurement. 
Otherwise: Last evaluable measurement before first QWO (CCH-aaes) 
injection on Day 1.
Date of First QWO Injection
Day 1 visit date


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Table 11: 
Subject Level Derived Dataset Variables (Continued)
Variable
Definition
Difference in number of 
QWO injections 
(number of QWO injections in left buttock) – (number of QWO injections in 
right buttock).
Last Date in Study
Date of last visit where subject was seen by the investigator.
If subject was lost to follow-up, then last date of contact. If the subject had 
contact with the site after the final visit (eg, to follow-up on an AE), the last 
visit date will still be used as last date in the study.
Time in Study
Last Date in Study – Date of First Injection + 1
AE=Adverse event; BMI=Body mass index
6.2.
Safety Variables
6.2.1.
Adverse Events
Adverse events will be organized in 2 different ways: by event and by subject. The by event 
dataset will include all the characteristics of the event obtained on the eCRF plus the derived 
variables presented in Table 12. A second by event dataset will be created for the AE duration 
analysis. This duration dataset will contain only the subject number, treatment session, body 
system classification, preferred term, and duration.
Table 12: 
Adverse Event Variables by Event
Variable
Values/Definition
Treatment-Emergent
AE with a start date after the first dose of study medication
QWO-Related
If relationship to QWO (CCH-aaes) is reported as possible, probable or missing; ‘unlikely 
related’ AE will be classified as not a drug-related AE. 
Mitigation-Related
If relationship to study mitigation only is reported as possible, probable or missing; 
‘unlikely related’ AE will be classified as not a mitigation-related AE.
Onset Day
AE Start Date - Date of First Injection + 1
Duration
AE Stop Date - AE Start Date + 1
AE=Adverse event
The by-subject dataset will summarize all the AE events for a subject and will include the 
variables presented in Table 13. The same variables will be computed for TEAEs and treatment-
related AEs.
Table 13: 
Adverse Event Variables by Subject
Variable
Values/Definition
Total AEs
Sum of number of AEs the subject reported
Total Mild AEs
Sum of number of mild AEs the subject reported
Total Moderate AEs
Sum of number of moderate AEs the subject reported
Total Severe AEs
Sum of number of severe AEs the subject reported
Had AE
Flag (Y/N) to indicate subject had at least 1 AE
Had Severe AE
Flag (Y/N) to indicate subject had at least 1 AE of moderate or severe severity
Had SAE
Flag (Y/N) to indicate subject had at least 1 serious AE


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Table 13: 
Adverse Event Variables by Subject (Continued)
Variable
Values/Definition
Had AE Leading to 
Discontinuation
Flag (Y/N) to indicate subject had at least 1 AE that led to discontinuation from the 
study
Had AE Leading to 
Interruption/Withdrawal 
of QWO (CCH-aaes)
Flag (Y/N) to indicate subject had at least 1 AE that led to interruption/withdrawal of 
QWO (CCH-aaes)
Had AE Leading to 
Interruption/Withdrawal 
of Mitigation
Flag (Y/N) to indicate subject had at least 1 AE that led to interruption/withdrawal of 
Mitigation treatment
AE=Adverse event; SAE=Serious adverse event; Y/N=Yes/No
6.3.
Imputation of Partial Dates
Study visit dates, birthdates, informed consent date, injection dates/times, all assessment dates, 
and date of completion/last contact date must be complete dates; no imputations will be done. No 
imputations will be done for partial medical history onset/resolution dates, partial 
alcohol/tobacco stop dates, missing date of last menstrual period, partial AEs onset/end dates and 
partial concomitant medication/procedure start/stop dates. All AEs with a missing onset day will 
be considered treatment-emergent except if the onset month/year is prior to the first injection 
date. All medications/procedures with a missing onset and stop day will be considered 
concomitant except if the stop month/year is prior to the first injection date. 
6.4.
Relative Study Day
Relative study day will be computed for each visit and for each AE. For visits or events 
occurring on or after the Day 1 visit, relative study day will be the date of visit (event) minus the 
date of first QWO (CCH-aaes) injection + 1. For visits or events that occur prior to the Day 1 
visit, the relative study day will be the date of visit (event) minus the date of first QWO (CCH-
aaes) injection. 
6.5.
Conventions and Algorithms
6.5.1.
Summary Tables/Subject Listings Conventions
Summary tables, subject listings, graphs and any supportive SAS output will include a “footer” 
of explanatory notes that will indicate, when applicable: 

Date of data extraction 

Date and time of output generation

SAS program name, including the path, that generates the output
Null summary tables will be presented with a note stating that “No Subjects Met Criteria.” 
The summary tables will clearly indicate the effective sample size per treatment group. All 
summary tables involving percentages will round the percentages off to 1 decimal place. All 
summary tables involving descriptive statistics of continuous variables will round the mean and 
median to 1 decimal place more than the variable’s standard form and round the standard 


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deviation to 2 decimal places more than the variable’s standard form. The standard form of a 
percent change variable is one decimal place.
When calculating percentages, the denominator will be based on the number of non-missing 
responses. The number of missing responses will be presented as a count only. If the 
denominator is expected to change over time, then the denominator used to calculate the 
percentage should be presented on the table. Any subject and/or buttock record removed from an 
analysis will be noted at the bottom of the table along with the reason for removal. These 
subjects and/or buttock records will also be listed.
When summarizing AEs, and vital signs, subjects with multiple occurrences of an event will be 
counted only once in the summary. When AEs are summarized by severity, if the subject has 
multiple occurrences of the same AE, the most severe will be used for the summary.
By-subject listings for AEs and vital signs will be provided. Other by-subject listings will be 
provided as support for summary tables and serve as a data source substitute when a summary 
table is deemed either inappropriate or unnecessary. All subject listings will be organized by 
investigational site and cohort, sorted by subject number. When applicable, the subject listings 
will include the visit date, and days relative to the start of first treatment and start of treatment 
session. 
7.
INTERIM ANALYSES
An interim analysis (IA) will be conducted at a time point to be determined after at least 25% of 
subjects of the count of total planned subjects have received treatment and completed Day 22 
Visit assessments.
8.
SAMPLE SIZE DETERMINATIONS
The proposed sample size is approximately 48 subjects. The sample size is based on evaluation 
of mitigation treatment in 6 cohorts of approximately 8 subjects each. Five (5) treatment cohorts 
will receive mitigation treatments and 1 treatment cohort will not receive mitigation treatment.
9.
TABLES, LISTINGS, AND GRAPH SHELLS
The layouts of the summary tables, subject listings, and graphs are presented in SAP Module 2. 
These layouts incorporate all the appropriate table titles, table numbers, and footnotes. 
10.
CHANGE FROM PROTOCOL
Table 14 lists any significant changes in the SAP from what is proposed in the protocol.
Table 14: 
Changes from Protocol
Text in Protocol
Change in SAP
Justification


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11.
REVISION HISTORY
Non-editorial changes made to any of the sections of this SAP will be recorded in Table 15. All 
significant changes require a new signature page be completed.
Table 15: 
Revision History
Description of Change/Reason for Change
Document 
Version Number 
Before Change
Date of Change
Original
N/A
N/A
12.
REFERENCES
1. US Food and Drug Administration. Guidance for Industry, E9 Statistical Principles for 
Clinical Studies (ICH E9); 1998:30.
2. Clinical Study Protocol: MOBI: A Phase 4, Open-Label Study to Assess Effects of 
Mitigation Treatments on Bruising of CCH-aaes Treatment of Buttock Cellulite in 
Females. Dated: November 18, 2020.
3. Hexsel DM, Dal’Forno T, Hexsel CL. A validated photonumeric cellulite severity scale. J 
Eur Acad Dermatol Venereol. 2009;23 (5):523-8.
4. Nürnberger F, Müller G. So-called cellulite: an invented disease. J Dermatol Surg Oncol. 
1978;4(3):221-9.
13.
TABLES, LISTINGS, AND GRAPH SHELLS 
The layouts of the summary tables, subject listings, and graphs are presented in SAP Module 2. 
These layouts incorporate all the appropriate table titles, table numbers, and footnotes.


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SAP MODULE 2 – TABLE, LISTING AND GRAPH SHELLS
Protocol No. EN3835-401
MOBI: A PHASE 4, OPEN-LABEL STUDY TO ASSESS EFFECTS OF 
MITIGATION TREATMENTS ON BRUISING OF CCH-AAES 
TREATMENT OF BUTTOCK CELLULITE IN ADULT FEMALES
Version 1.0
February 10, 2021
Endo Pharmaceuticals Inc.
1400 Atwater Drive
Malvern, PA 19355
USA


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LIST OF TABLES
Table 14.1.1
Subject Disposition
Table 14.1.2
Demographic and Baseline Characteristics - Safety Population
Table 14.1.3
CR-PCSS Cellulite Severity Rating and Hexsel CSS Subsection D Score of 
Left/Right Buttock at Screening - Safety Population
Table 14.1.4.1.1
Prior Medications - Safety Population
Table 14.1.4.1.2
Concomitant Medications - Safety Population
Table 14.1.4.2.1
Prior Procedures - Safety Population
Table 14.1.4.2.2
Concomitant Procedures - Safety Population
Table 14.2.1.1
Treatment Exposure – QWO (CCH-aaes) - Safety Population
Table 14.2.1.2
Overview of Treatment – QWO (CCH-aaes) - Safety Population
Table 14.2.2
Treatment Exposure – Mitigation Treatment, Treated Buttock [1] - Safety 
Population
Table 14.2.3.1
Observed and Change from Baseline in Investigator Assessment of 
Bruising Severity, by Visit - Evaluable Population
Table 14.2.3.2
Summary of Investigator-Global Aesthetic Improvement Scale (I-GAIS) 
Ratings and 1-Level Responders by Visit - Evaluable Population
Table 14.2.3.3
Summary of Investigator-Bruising Improvement Scale (I-BIS) Ratings by 
Visit - Evaluable Population
Table 14.2.3.4
Summary of Subject-Bruising Improvement Scale (S-BIS) Ratings by 
Visit - Evaluable Population
Table 14.2.3.5
Summary of Patient Bothered by Bruising Ratings by Visit - Evaluable 
Population
 
Table 14.3.1.1
Overall Summary of Treatment-Emergent Adverse Events - Safety 
Population
Table 14.3.1.2
Overall Summary of QWO-Related Adverse Events - Safety Population
Table 14.3.1.3
Overall Summary of Mitigation-Related Adverse Events - Safety 
Population
Table 14.3.2.1
Treatment-Emergent Adverse Events by System Organ Class and Preferred 
Term - Safety Population
Table 14.3.2.2
QWO-Related Adverse Events by System Organ Class and Preferred 
Term - Safety Population
Table 14.3.2.3
Mitigation-Related Adverse Events by System Organ Class and Preferred 
Term - Safety Population


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Table 14.3.3.1
Treatment-Emergent Adverse Events by System Organ Class, Preferred 
Term and Severity - Safety Population
Table 14.3.3.2
QWO-Related Adverse Events by System Organ Class, Preferred Term, 
and Severity - Safety Population
Table 14.3.3.3
Mitigation-Related Adverse Events by System Organ Class, Preferred 
Term, and Severity - Safety Population
Table 14.3.4.1
Summary of Serious Adverse Events by Frequency - Safety Population
Table 14.3.5.1
Summary of Most Common (>=5%) Non-Serious Treatment-Emergent 
Adverse Events by Frequency - Safety Population
Table 14.4.1.1
Body Weight (kg) and BMI (kg/m^2) - Safety Population
Table 14.4.2.1
Vital Signs: Systolic Blood Pressure (mmHg) - Safety Population
Table 14.4.2.2
Vital Signs: Diastolic Blood Pressure (mmHg) - Safety Population
Table 14.4.2.3
Vital Signs: Body Temperature (oC) - Safety Population
Table 14.4.2.4
Vital Signs: Pulse Rate (beats per minute) - Safety Population


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LIST OF DATA LISTINGS
Listing 16.2.1.1
Subject Visits and Disposition
Listing 16.2.1.2
Discontinued Subjects - All Subjects
Listing 16.2.1.3
Screen Failures - All Subjects
Listing 16.2.1.4
Inclusion/Exclusion Criteria - All Subjects
Listing 16.2.2
Protocol Deviations - All Subjects
Listing 16.2.3
Exclusion from Analysis Population - All Enrolled Subjects
Listing 16.2.4.1
Demographics - All Enrolled Subjects
Listing 16.2.4.2
Baseline Characteristics - All Enrolled Subjects
Listing 16.2.4.3
Medical and Surgical History - All Enrolled Subjects
Listing 16.2.4.4
Prior and Concomitant Medications - All Enrolled Subjects
Listing 16.2.4.5
Prior and Concomitant Procedures - All Enrolled Subjects
Listing 16.2.5.1
Treatment Administration: QWO (CCH-aaes) - All Enrolled Subjects
Listing 16.2.5.2
Treatment Administration: Mitigation Treatment - All Enrolled Subjects
Listing 16.2.6.1
Investigator Assessment of Bruising Severity - All Enrolled Subjects
Listing 16.2.6.2
Investigator Global Aesthetic Improvement Scale (I-GAIS) 
Assessment - All Enrolled Subjects
Listing 16.2.6.3
Investigator Bruising Improvement Scale (I-BIS) Assessment - All 
Enrolled Subjects
Listing 16.2.6.4
Subject Bruising Improvement Scale (S-BIS) Assessment - All Enrolled 
Subjects
Listing 16.2.6.5
Patient Bother by Bruising Assessment - All Enrolled Subjects
Listing 16.2.6.7
Digital Photography - All Enrolled Subjects
Listing 16.2.7.1
Adverse Events - All Enrolled Subjects
Listing 16.2.7.2
Deaths - All Enrolled Subjects
Listing 16.2.7.3
Non-fatal Serious Adverse Events - All Enrolled Subjects
Listing 16.2.7.4
Non-serious AEs Leading to either QWO or Mitigation Treatment 
Interruption or Discontinuation - All Enrolled Subjects
Listing 16.2.7.5
Non-serious AEs Leading to either QWO or Mitigation Treatment 
Withdrawn - All Enrolled Subjects
Listing 16.2.8.1
Vital Signs - All Enrolled Subjects
Listing 16.2.8.2
Physical Examinations - All Enrolled Subjects


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 43
Table 14.1.1
Subject Disposition
Statistic
Cohort 1
No Mitigation
Cohort 2
Compression
...
Cohort 6
PDL Treatment
Overall
Screened Subjects [1]
n
xx
  Screen Failures [2]
n (%)
xx (xx.x)
Enrolled Subjects [3]
n
xx
Xx
…
xx
xx
Safety Population [4]
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Evaluable Population [5]
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Study Completion Status
  Completed Study [6]
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Withdrawn from Study
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    Adverse Event
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    Death
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    Protocol Non-compliance
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    Withdrawal by Subject
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    Investigator Decision
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    Sponsor Decision
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    Subject Moved
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    Pregnancy
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    Lost to Follow-Up
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    Other
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
[1] All subjects who signed informed consent.
[2] Percentages for screen failure subjects are based on the number of screened subjects in each column.
[3] All subjects who were enrolled and allocated to one of the 6 mitigation cohorts. Percentages were based on all enrolled subjects.
[4] All enrolled subjects who received at least one injection of QWO (CCH-aaes) with or without mitigation treatment.
[5] All enrolled subjects who received at least one injection of QWO (CCH-aaes) with or without mitigation treatment and have at least 
one bruising assessment after the first dose of QWO (CCH-aaes).
[6] Received at least one injection of QWO (CCH-aaes) with or without mitigation treatment and completed the Day 71 visit.
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: please include columns for cohorts 1-3 on page 1, and columns for cohorts 4-6 and Overall on page 2 if it is 
impossible to put all columns in one page. Cohort column headers should read: “Cohort 1 No Mitigation”, “Cohort 2 Compression”, 
“Cohort 3 Cold Packs”, “Cohort 4 Arnica Patches”, “Cohort 5 INhance Serum”, “Cohort 6 PDL Treatment”.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 44
Table 14.1.2
Demographic and Baseline Characteristics
Safety Population
Statistic
Cohort 1
No Mitigation
(N=xxx)
Cohort 2
Compression
(N=xxx)
...
Cohort 6
PDL Treatment
(N=xxx)
Overall
(N=xxx)
Age (Years)
n
xx
Xx
xx
xx
Mean
xx.x
xx.x
…
xx.x
xx.x
SD
xx.xx
xx.xx
…
xx.xx
xx.xx
Median
xx.x
xx.x
…
xx.x
xx.x
Min
xx
Xx
xx
xx
Max
xx
Xx
xx
xx
Age Group 
  18-<25 Years
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  25-<35 Years
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  35-50 Years
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Gender
  Female
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Race
  American Indian/Alaskan Native
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Asian
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Black of African American
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Native Hawaiian or Other Pacific 
Islander
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  White
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Other
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Ethnicity
  Hispanic or Latino
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Not Hispanic and Non-Latino
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 45
Table 14.1.2
Demographic and Baseline Characteristics
Safety Population
Statistic
Cohort 1
No Mitigation
(N=xxx)
Cohort 2
Compression
(N=xxx)
...
Cohort 6
PDL Treatment
(N=xxx)
Overall
(N=xxx)
Body Weight (kg)
n
xx
Xx
xx
xx
Mean
xx.x
xx.x
…
xx.x
xx.x
SD
xx.xx
xx.xx
…
xx.xx
xx.xx
Median
xx.x
xx.x
…
xx.x
xx.x
Min
xx
Xx
xx
xx
Max
xx
Xx
xx
xx
Body Height (cm)
n
xx
Xx
xx
xx
Mean
xx.x
xx.x
…
xx.x
xx.x
SD
xx.xx
xx.xx
…
xx.xx
xx.xx
Median
xx.x
xx.x
…
xx.x
xx.x
Min
xx
Xx
xx
xx
Max
xx
Xx
xx
xx
BMI (kg/m^2)
n
xx
Xx
xx
xx
Mean
xx.x
xx.x
…
xx.x
xx.x
SD
xx.xx
xx.xx
…
xx.xx
xx.xx
Median
xx.x
xx.x
…
xx.x
xx.x
Min
xx
Xx
xx
xx
Max
xx
Xx
xx
xx
BMI Group
  Normal Weight (< 25.0 kg/m^2)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Overweight (>= 25.0 kg/m^2)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 46
Table 14.1.2
Demographic and Baseline Characteristics
Safety Population
Statistic
Cohort 1
No Mitigation
(N=xxx)
Cohort 2
Compression
(N=xxx)
...
Cohort 6
PDL Treatment
(N=xxx)
Overall
(N=xxx)
Skin Category (Fitzpatrick Scale) [1]
  I (Pale White)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  II (Fair)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  III (Darker White)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Alcohol Use
  Never
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Current
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Former
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Tobacco Use
  Never
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Current
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Former
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
[1] Only subjects with a Fitzpatrick skin rating of I-III at the Screening Visit were eligible for the study as per the protocol 
inclusion criteria.
Note: Safety Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment.  
Datasets (extraction):  status(ddmmmyyyy),
       ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: please include columns for cohorts 1-3 on page 1, and columns for cohorts 4-6 and Overall on page 2 if it is 
impossible to put all columns in one page. Cohort column headers should read: “Cohort 1 No Mitigation”, “Cohort 2 Compression”, 
“Cohort 3 Cold Packs”, “Cohort 4 Arnica Patches”, “Cohort 5 INhance Serum”, “Cohort 6 PDL Treatment”.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 47
Table 14.1.3
CR-PCSS Cellulite Severity Rating and Hexsel CSS Subsection D Score of Left/Right Buttock at Screening
Safety Population
Buttock
Parameter
Statistic
Cohort 1
No Mitigation
(N=xxx)
Cohort 2
Compression
(N=xxx)
...
Cohort 6
PDL Treatment
(N=xxx)
Overall
(N=xxx)
Left
CR-PCSS Rating [1]
  3 (Moderate)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Hexsel CSS Subsection D Score [2]
  0 (Absence of flaccidity or sagging 
of skin)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  1 (Slightly draped appearance)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Right
CR-PCSS Rating [1]
  3 (Moderate)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Hexsel CSS Subsection D Score [2]
  0 (Absence of flaccidity or sagging 
of skin)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  1 (Slightly draped appearance)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
[1] CR-PCSS = Clinician-Reported Photonumeric Cellulite Severity Scale. Only subjects with a baseline CR-PCSS rating of 3 (Moderate) 
on each buttock at the Screening Visit were included in the study as per the protocol inclusion criteria.
[2] CSS = Cellulite Severity Scale. Only subjects with a baseline Hexsel CSS Subsection D score of 0 or 1 on each buttock at the 
Screening Visit were included in the study as per the protocol inclusion criteria.
Note: Safety Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment.     
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: please include columns for cohorts 1-3 on page 1, and columns for cohorts 4-6 and Overall on page 2 if it is 
impossible to put all columns in one page. Cohort column headers should read: “Cohort 1 No Mitigation”, “Cohort 2 Compression”, 
“Cohort 3 Cold Packs”, “Cohort 4 Arnica Patches”, “Cohort 5 INhance Serum”, “Cohort 6 PDL Treatment”.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 48
Table 14.1.4.1.1
Prior Medications
Safety Population
Drug Class/
  Preferred Term [1] 
Statistic
Cohort 1
No Mitigation
(N=xxx)
Cohort 2
Compression
(N=xxx)
...
Cohort 6
PDL Treatment
(N=xxx)
Overall
(N=xxx)
Number of subjects with at least one 
prior medication [2]
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Drug Class 1
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Preferred Term 1
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Preferred Term 2
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Preferred Term 3
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Drug Class 2
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Preferred Term 4
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Preferred Term 5
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Preferred Term 6
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Preferred Term 7
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
[1] Drug class and preferred term were coded using WHO-drug dictionary (Version xxxxx).
[2] Prior medications are any medication reported as taken prior to Day 1.  
Note: Safety Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment.     
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: please include columns for cohorts 1-3 on page 1, and columns for cohorts 4-6 and Overall on page 2 if it is 
impossible to put all columns in one page. Cohort column headers should read: “Cohort 1 No Mitigation”, “Cohort 2 Compression”, 
“Cohort 3 Cold Packs”, “Cohort 4 Arnica Patches”, “Cohort 5 INhance Serum”, “Cohort 6 PDL Treatment”. Table should be 
sorted alphabetically by Drug Class/Preferred Term.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 49
Table 14.1.4.1.2
Concomitant Medications
Safety Population
Drug Class/
  Preferred Term [1] 
Statistic
Cohort 1
No Mitigation
(N=xxx)
Cohort 2
Compression
(N=xxx)
...
Cohort 6
PDL Treatment
(N=xxx)
Overall
(N=xxx)
Number of subjects with at least one 
concomitant medication [2]
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Drug Class 1
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Preferred Term 1
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Preferred Term 2
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Preferred Term 3
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Drug Class 2
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Preferred Term 4
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Preferred Term 5
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Preferred Term 6
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Preferred Term 7
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
[1] Drug class and preferred term were coded using WHO-drug dictionary (Version xxxxx).
[2] Concomitant medications are any medication reported as taken on or after Day 1 (Baseline Visit) through Day 71/Early Termination 
Visit. Mitigation medications provided after each QWO (CCH-aaes) treatment session may also be included as concomitant medications.   
Note: Safety Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment.     
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: please include columns for cohorts 1-3 on page 1, and columns for cohorts 4-6 and Overall on page 2 if it is 
impossible to put all columns in one page. Cohort column headers should read: “Cohort 1 No Mitigation”, “Cohort 2 Compression”, 
“Cohort 3 Cold Packs”, “Cohort 4 Arnica Patches”, “Cohort 5 INhance Serum”, “Cohort 6 PDL Treatment”. Table should be 
sorted alphabetically by Drug Class/Preferred Term.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 50
Table 14.1.4.2.1
Prior Procedures
Safety Population
Procedure 
Statistic
Cohort 1
No Mitigation
(N=xxx)
Cohort 2
Compression
(N=xxx)
...
Cohort 6
PDL Treatment
(N=xxx)
Overall
(N=xxx)
Number of subjects with at least one 
prior procedure [1]
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
xxxxxxxxxxxx
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
xxxxxxxxxxxx
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
xxxxxxxxxxxx
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
xxxxxxxxxxxx
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
xxxxxxxxxxxx
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
xxxxxxxxxxxx
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
xxxxxxxxxxxx
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
xxxxxxxxxxxx
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
xxxxxxxxxxxx
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
[1] A prior procedure is any procedure/nondrug therapy reported as received prior to Day 1.
Note: Safety Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment.     
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: please include columns for cohorts 1-3 on page 1, and columns for cohorts 4-6 and Overall on page 2 if it is 
impossible to put all columns in one page. Cohort column headers should read: “Cohort 1 No Mitigation”, “Cohort 2 Compression”, 
“Cohort 3 Cold Packs”, “Cohort 4 Arnica Patches”, “Cohort 5 INhance Serum”, “Cohort 6 PDL Treatment”. Table should be 
sorted alphabetically by Drug Class/Preferred Term.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 51
Table 14.1.4.2.2
Concomitant Procedures
Safety Population
Procedure 
Statistic
Cohort 1
No Mitigation
(N=xxx)
Cohort 2
Compression
(N=xxx)
...
Cohort 6
PDL Treatment
(N=xxx)
Overall
(N=xxx)
Number of subjects with at least one 
concomitant procedure [1]
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
xxxxxxxxxxxx
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
xxxxxxxxxxxx
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
xxxxxxxxxxxx
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
xxxxxxxxxxxx
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
xxxxxxxxxxxx
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
xxxxxxxxxxxx
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
xxxxxxxxxxxx
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
xxxxxxxxxxxx
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
xxxxxxxxxxxx
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
[1] A concomitant procedure is any procedure/nondrug therapy received on or after Day 1 (Baseline Visit) through Day 71/Early
Termination Visit. Mitigation procedures administered after each QWO (CCH-aaes) treatment session may also be included as 
concomitant procedures.   
Note: Safety Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment.     
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: please include columns for cohorts 1-3 on page 1, and columns for cohorts 4-6 and Overall on page 2 if it is 
impossible to put all columns in one page. Cohort column headers should read: “Cohort 1 No Mitigation”, “Cohort 2 Compression”, 
“Cohort 3 Cold Packs”, “Cohort 4 Arnica Patches”, “Cohort 5 INhance Serum”, “Cohort 6 PDL Treatment”. Table should be 
sorted alphabetically by Drug Class/Preferred Term.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 52
Table 14.2.1.1
Treatment Exposure – QWO (CCH-aaes)
Safety Population
Cohort 1
No Mitigation
(N=xxx)
...
Cohort 6
PDL Treatment
(N=xxx)
Parameter
Statistic
Left 
Right
Left 
Right
Treatment Sessions Per Subject
  One QWO Treatment Session
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Two QWO Treatment Sessions
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  Three QWO Treatment Sessions
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Treatment Session 1 (Day 1)
  QWO Treatment Done
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  QWO Treatment Not Done
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Treatment Session 2 (Day 22)
  QWO Treatment Done
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  QWO Treatment Not Done
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Treatment Session 3 (Day 43)
  QWO Treatment Done
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  QWO Treatment Not Done
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Note: Safety Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment.     
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: please include columns for cohorts 1-3 on page 1, and columns for cohorts 4-6 on page 2 if it is impossible to put 
all columns in one page. Cohort column headers should read: “Cohort 1 No Mitigation”, “Cohort 2 Compression”, “Cohort 3 Cold 
Packs”, “Cohort 4 Arnica Patches”, “Cohort 5 INhance Serum”, “Cohort 6 PDL Treatment”.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 53
Table 14.2.1.2
Overview of Treatment – QWO (CCH-aaes)
Safety Population
Visit
Statistic
Cohort 1
No Mitigation
(N=xxx)
...
Cohort 6
PDL Treatment
(N=xxx)
  Parameter
Left
Right
Difference 
[1]
Left
Right
Difference 
[1]
QWO Treatment Session 1 (Day 1)
  Number of QWO Injections
n 
Xx
xx
xx
…
xx
xx
xx
Mean
xx.x
xx.x
xx.x
…
xx.x
xx.x
xx.x
SD
xx.xx
xx.xx
xx.xx
…
xx.xx
xx.xx
xx.xx
Median
xx.x
xx.x
xx.x
…
xx.x
xx.x
xx.x
Min
Xx
xx
xx
xx
xx
xx
Max
Xx
xx
xx
xx
xx
xx
QWO Treatment Session 2 (Day 22)
  Number of QWO Injections
n 
Xx
xx
xx
…
xx
xx
xx
Mean
xx.x
xx.x
xx.x
…
xx.x
xx.x
xx.x
SD
xx.xx
xx.xx
xx.xx
…
xx.xx
xx.xx
xx.xx
Median
xx.x
xx.x
xx.x
…
xx.x
xx.x
xx.x
Min
Xx
xx
xx
xx
xx
xx
Max
Xx
xx
xx
xx
xx
xx
QWO Treatment Session 3 (Day 43)
  Number of QWO Injections
n 
Xx
xx
xx
…
xx
xx
xx
Mean
xx.x
xx.x
xx.x
…
xx.x
xx.x
xx.x
SD
xx.xx
xx.xx
xx.xx
…
xx.xx
xx.xx
xx.xx
Median
xx.x
xx.x
xx.x
…
xx.x
xx.x
xx.x
Min
Xx
xx
xx
xx
xx
xx
Max
Xx
xx
xx
xx
xx
xx
[1] Difference = (number of QWO injections in left buttock) – (number of QWO injections in right buttock). Difference was calculated 
for each subject for each QWO treatment session.
Note: Safety Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment.     
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: please include columns for cohorts 1-3 on page 1, and columns for cohorts 4-6 and Overall on page 2 if it is 
impossible to put all columns in one page. Cohort column headers should read: “Cohort 1 No Mitigation”, “Cohort 2 Compression”, 
“Cohort 3 Cold Packs”, “Cohort 4 Arnica Patches”, “Cohort 5 INhance Serum”, “Cohort 6 PDL Treatment”.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 54
Table 14.2.2
Treatment Exposure – Mitigation Treatment, Treated Buttock [1]
Safety Population
Visit
  Mitigation Treatment Type
Statistic
Cohort 2
Compression
(N=xxx)
...
Cohort 6
PDL Treatment
(N=xxx)
Mitigation Treatment Sessions Per Subject
  One Mitigation Treatment Session
n (%)
xx (xx.x)
…
xx (xx.x)
  Two Mitigation Treatment Sessions
n (%)
xx (xx.x)
…
xx (xx.x)
  Three Mitigation Treatment Sessions
n (%)
xx (xx.x)
…
xx (xx.x)
Treatment Session 1 (Day 1)
  Compression garment
n (%)
xx (xx.x)
…
xx (xx.x)
  Instant cold packs
n (%)
xx (xx.x)
…
xx (xx.x)
  Arnica patches
n (%)
xx (xx.x)
…
xx (xx.x)
  INhance post-injection serum [2]
n (%)
xx (xx.x)
…
xx (xx.x)
  PDL Treatment [3]
n (%)
xx (xx.x)
…
xx (xx.x)
Treatment Session 2 (Day 22)
  Compression garment
n (%)
xx (xx.x)
…
xx (xx.x)
  Instant cold packs
n (%)
xx (xx.x)
…
xx (xx.x)
  Arnica patches
n (%)
xx (xx.x)
…
xx (xx.x)
  INhance post-injection serum [2]
n (%)
xx (xx.x)
…
xx (xx.x)
  PDL Treatment [3]
n (%)
xx (xx.x)
…
xx (xx.x)
Treatment Session 3 (Day 43)
  Compression garment
n (%)
xx (xx.x)
…
xx (xx.x)
  Instant cold packs
n (%)
xx (xx.x)
…
xx (xx.x)
  Arnica patches
n (%)
xx (xx.x)
…
xx (xx.x)
  INhance post-injection serum [2]
n (%)
xx (xx.x)
…
xx (xx.x)
  PDL Treatment [3]
n (%)
xx (xx.x)
…
xx (xx.x)
[1] For Cohort 2, mitigation treatment was administered to both left and right buttocks. For Cohorts 3-6, mitigation treatment was 
administered to right buttock only.  
[2] INhance post-injection serum with TriHex technology.
[3] PDL = pulse dye laser.
Note: By design, Cohort 1 did not receive any mitigation treatment.
Safety Population includes all subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation treatment.  
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: please include columns for cohorts 2-3 on page 1, and columns for cohorts 4-6 and Overall on page 2 if it is 
impossible to put all columns in one page. Cohort column headers should read: “Cohort 2 Compression”, “Cohort 3 Cold Packs”, 
“Cohort 4 Arnica Patches”, “Cohort 5 INhance Serum”, “Cohort 6 PDL Treatment”.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 55
Table 14.2.3.1 
Observed and Change from Baseline in Investigator Assessment of Bruising Severity, by Visit
Evaluable Population
Visit 
Cohort 1
No Mitigation
(N=xxx)
...
Cohort 6
PDL Treatment
(N=xxx)
  Bruising Severity Rating [1]
Statistic [2]
Left
Right
Left
Right
Baseline [3]
  Number of Subjects Evaluated
n
xx
xx
…
xx
xx
  0 (None or almost none)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  1 (Mild)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  2 (Moderate) 
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  3 (Severe)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  4 (Very Severe) 
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  
Mean
xx.x
xx.x
…
xx.x
xx.x
SD
xx.xx
xx.xx
…
xx.xx
xx.xx
Day 2
  Number of Subjects Evaluated
n
xx
xx
…
xx
xx
  0 (None or almost none)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  1 (Mild)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  2 (Moderate) 
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  3 (Severe)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  4 (Very Severe) 
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  
Mean
xx.x
xx.x
…
xx.x
xx.x
SD
xx.xx
xx.xx
…
xx.xx
xx.xx
Change from Baseline at Day 2
  Number of Subjects Evaluated
n
xx
xx
…
xx
xx
  -4
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  -3
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  -2
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  -1
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  0
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  +1
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  +2
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  +3
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  +4
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  
Mean
xx.x
xx.x
…
xx.x
xx.x
SD
xx.xx
xx.xx
…
xx.xx
xx.xx
[1] Results as reported using the Investigator Assessment of Bruising Severity Scale.
[2] Percentages are based on number of subjects with non-missing assessments at an evaluation visit.
[3] Based on results recorded at the Baseline Visit (Day 1).
[4] Based on results recorded at the Day 22 Visit, before injection.
Note: By design, Cohort 1 did not receive any mitigation treatment. For Cohort 2, mitigation treatment was administered to both left 
and right buttocks. For Cohorts 3-6, mitigation treatment was administered to right buttock only.   
    Evaluable Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment and have at least one bruising assessment after the first dose of QWO (CCH-aaes).  


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 56
Table 14.2.3.1 
Observed and Change from Baseline in Investigator Assessment of Bruising Severity, by Visit
Evaluable Population
Visit 
Cohort 1
No Mitigation
(N=xxx)
...
Cohort 6
PDL Treatment
(N=xxx)
  Bruising Severity Rating [1]
Statistic [2]
Left
Right
Left
Right
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: please include columns for cohorts 1-2 on page 1, columns for cohorts 3-4 on page 2, and columns for cohorts 5-
6 on page 3. Cohort column headers should read: “Cohort 1 No Mitigation”, “Cohort 2 Compression”, “Cohort 3 Cold Packs”, 
“Cohort 4 Arnica Patches”, “Cohort 5 INhance Serum”, “Cohort 6 PDL Treatment”.
Repeat this table for Bruising Level ratings for days 4, 7, 14, and 22, and change from baseline at days 4, 7, 14 and 22.  For Day 22, 
please include footnote [4] (i.e. display should be “Day 22 [4]” and “Change from Baseline at Day 22 [4]”).


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 57
Table 14.2.3.2
Summary of Investigator-Global Aesthetic Improvement Scale (I-GAIS) Ratings and 1-Level Responders by Visit
Evaluable Population
Visit 
Cohort 1
No Mitigation
(N=xxx)
...
Cohort 6
PDL Treatment
(N=xxx)
  Parameter
Statistic 
[1]
Left
Right
Left
Right
Day 22 [2]
  I-GAIS Rating [3]
  Number of Subjects Evaluated
n
  xx
  xx
xx
xx
    +3 (Very much improved)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    +2 (Much improved)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    +1 (Improved)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    0 (No change)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    -1 (Worse)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    -2 (Much worse)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    -3 (Very much worse)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
     
Mean
xx.x
xx.x
xx.x
xx.x
SD
xx.xx
xx.xx
xx.xx
xx.xx
  1-level I-GAIS Responder [4]
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Day 43
  I-GAIS Rating [3]
    Number of Subjects Evaluated
n
  xx
  xx
xx
xx
    +3 (Very much improved)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    +2 (Much improved)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    +1 (Improved)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    0 (No change)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    -1 (Worse)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    -2 (Much worse)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    -3 (Very much worse)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Mean
xx.x
xx.x
xx.x
xx.x
SD
xx.xx
xx.xx
xx.xx
xx.xx
  1-level I-GAIS Responder [4]
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Day 71
  I-GAIS Rating [3]
    Number of Subjects Evaluated
n
  xx
  xx
xx
xx
    +3 (Very much improved)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    +2 (Much improved)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    +1 (Improved)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    0 (No change)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    -1 (Worse)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    -2 (Much worse)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
    -3 (Very much worse)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Mean
xx.x
xx.x
xx.x
xx.x
SD
xx.xx
xx.xx
xx.xx
xx.xx


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 58
Table 14.2.3.2
Summary of Investigator-Global Aesthetic Improvement Scale (I-GAIS) Ratings and 1-Level Responders by Visit
Evaluable Population
Visit 
Cohort 1
No Mitigation
(N=xxx)
...
Cohort 6
PDL Treatment
(N=xxx)
  Parameter
Statistic 
[1]
Left
Right
Left
Right
  1-level I-GAIS Responder [4]
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
[1] Percentages are based on number of subjects with non-missing assessments at an evaluation visit.
[2] Based on results recorded at the Day 22 visit, before injection.
[3] I-GAIS = Investigator–Global Aesthetic Improvement Scale.
[4] A subject is considered a 1-level I-GAIS Responder if they have an improved (+1, +2, +3) rating on the I-GAIS at an evaluation 
visit.
Note: By design, Cohort 1 did not receive any mitigation treatment. For Cohort 2, mitigation treatment was administered to both left 
and right buttocks.  For Cohorts 3-6, mitigation treatment was administered to right buttock only.
    Evaluable Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment and have at least one bruising assessment after the first dose of QWO (CCH-aaes).
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: please include columns for cohorts 1-2 on page 1, columns for cohorts 3-4 on page 2, and columns for cohorts 5-
6 on page 3.  Cohort column headers should read: “Cohort 1 No Mitigation”, “Cohort 2 Compression”, “Cohort 3 Cold Packs”, 
“Cohort 4 Arnica Patches”, “Cohort 5 INhance Serum”, “Cohort 6 PDL Treatment”.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 59
Table 14.2.3.3
Summary of Investigator-Bruising Improvement Scale (I-BIS) Ratings by Visit
Evaluable Population
Visit
  I-BIS Rating [1]
Statistic 
[2]
Cohort 3
Cold Packs
(N=xxx)
Cohort 4
Arnica Patches
(N=xxx)
Cohort 5
INhance Serum
(N=xxx)
Cohort 6
PDL Treatment
(N=xxx)
Day 2
  Number of Subjects Evaluated
n
xx
xx
xx
xx
  1 (Worse – more bruising)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  2 (Similar)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  3 (Improved – less bruising)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Day 4
  Number of Subjects Evaluated
n
xx
xx
xx
xx
  1 (Worse – more bruising)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  2 (Similar)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  3 (Improved – less bruising)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Day 7
  Number of Subjects Evaluated
n
xx
xx
xx
xx
  1 (Worse – more bruising)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  2 (Similar)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  3 (Improved – less bruising)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Day 14
  Number of Subjects Evaluated
n
xx
xx
xx
xx
  1 (Worse – more bruising)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  2 (Similar)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  3 (Improved – less bruising)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Day 22 [3]
  Number of Subjects Evaluated
n
xx
xx
xx
xx
  1 (Worse – more bruising)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  2 (Similar)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  3 (Improved – less bruising)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
[1] I-BIS = Investigator–Bruising Improvement Scale.  I-BIS Rating was directly obtained from the investigator’s assessment rating 
comparing the bruising of the mitigation-treated buttock to the untreated (with mitigation treatment) buttock.  The I-BIS 
assessment was not completed for subjects that did not receive mitigation treatment (Cohort 1) or subjects that received bilateral 
mitigation treatment (Cohort 2), as these subjects did not have an untreated buttock as a comparator.
[2] Percentages are based on number of subjects with non-missing assessments at an evaluation visit.
[3] Based on results recorded at the Day 22 visit, before injection.
Note: Evaluable Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without 
mitigation treatment and have at least one bruising assessment after the first dose of QWO (CCH-aaes).
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 60
Table 14.2.3.4
Summary of Subject-Bruising Improvement Scale (S-BIS) Ratings by Visit
Evaluable Population
Visit
  S-BIS Rating [1]
Statistic 
[2]
Cohort 3
Cold Packs
(N=xxx)
Cohort 4
Arnica Patches
(N=xxx)
Cohort 5
INhance Serum
(N=xxx)
Cohort 6
PDL Treatment
(N=xxx)
Day 2
  Number of Subjects Evaluated
n
xx
xx
xx
xx
  1 (Worse – more bruising)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  2 (Similar)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  3 (Improved – less bruising)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Day 4
  Number of Subjects Evaluated
n
xx
xx
xx
xx
  1 (Worse – more bruising)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  2 (Similar)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  3 (Improved – less bruising)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Day 7
  Number of Subjects Evaluated
n
xx
xx
xx
xx
  1 (Worse – more bruising)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  2 (Similar)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  3 (Improved – less bruising)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Day 14
  Number of Subjects Evaluated
n
xx
xx
xx
xx
  1 (Worse – more bruising)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  2 (Similar)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  3 (Improved – less bruising)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Day 22 [3]
  Number of Subjects Evaluated
n
xx
xx
xx
xx
  1 (Worse – more bruising)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  2 (Similar)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  3 (Improved – less bruising)
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
[1] S-BIS = Subject–Bruising Improvement Scale.  S-BIS Rating was directly obtained from the subject’s assessment rating comparing the 
bruising of the mitigation-treated buttock to the untreated (with mitigation treatment) buttock.  The S-BIS assessment was not 
completed for subjects that did not receive mitigation treatment (Cohort 1) or subjects that received bilateral mitigation 
treatment (Cohort 2), as these subjects did not have an untreated buttock as a comparator.
[2] Percentages are based on number of subjects with non-missing assessments at an evaluation visit.
[3] Based on results recorded at the Day 22 visit, before injection.
Note: Evaluable Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without 
mitigation treatment and have at least one bruising assessment after the first dose of QWO (CCH-aaes).
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
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Endo Pharmaceuticals Inc.
Page 61
Table 14.2.3.5
Summary of Patient Bothered by Bruising Ratings by Visit
Evaluable Population
Visit
Cohort 1
No Mitigation
(N=xxx)
…
Cohort 6
PDL Treatment
(N=xxx)
  Patient Bother Rating [1]
Statistic 
[2]
Left
Right
Left
Right
Day 4
  Number of Subjects Evaluated
n
xx
xx
xx
xx
  1 (Not at all bothered)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  2 (A little bothered)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  3 (Moderately bothered)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  4 (Extremely bothered)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Day 7
  Number of Subjects Evaluated
n
xx
xx
xx
xx
  1 (Not at all bothered)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  2 (A little bothered)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  3 (Moderately bothered)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  4 (Extremely bothered)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
Day 22 [3]
  Number of Subjects Evaluated
n
xx
xx
xx
xx
  1 (Not at all bothered)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  2 (A little bothered)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  3 (Moderately bothered)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
  4 (Extremely bothered)
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
xx (xx.x)
[1] Results as reported using the Patient Bothered by Bruising Scale.
[2] Percentages are based on number of subjects with non-missing assessments at an evaluation visit.
[3] Based on results recorded at the Day 22 visit, before injection.
Note: By design, Cohort 1 did not receive any mitigation treatment. For Cohort 2, mitigation treatment was administered to both left 
and right buttocks.  For Cohorts 3-6, mitigation treatment was administered to right buttock only.
    Evaluable Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment and have at least one bruising assessment after the first dose of QWO (CCH-aaes).
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: please include columns for cohorts 1-2 on page 1, columns for cohorts 3-4 on page 2, and columns for cohorts 5-
6 on page 3. Cohort column headers should read: “Cohort 1 No Mitigation”, “Cohort 2 Compression”, “Cohort 3 Cold Packs”, 
“Cohort 4 Arnica Patches”, “Cohort 5 INhance Serum”, “Cohort 6 PDL Treatment”.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 62
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: please include columns for cohorts 1-2 on page 1, columns for cohorts 3-4 on page 2, and columns for cohorts 5-
6 on page 3.  Cohort column headers should read: “Cohort 1 No Mitigation”, “Cohort 2 Compression”, “Cohort 3 Cold Packs”, 
“Cohort 4 Arnica Patches”, “Cohort 5 INhance Serum”, “Cohort 6 PDL Treatment”.
 
 


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 63
Table 14.3.1.1
Overall Summary of Treatment-Emergent Adverse Events
Safety Population
Parameter
Statistic
Cohort 1
No Mitigation
(N=xxx)
Cohort 2
Compression
(N=xxx)
…
Cohort 6
PDL Treatment
(N=xxx)
Total Number of TEAEs Reported [1]
n
xx
Xx
…
xx
  Total Number of Mild TEAEs [1]
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  Total Number of Moderate TEAEs [1] 
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  Total Number of Severe TEAEs [1]
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  Total Number of TEAEs related to QWO only [2]
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  Total Number of TEAEs related to Mitigation only [2] 
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  Total Number of TEAEs related to both QWO and Mitigation [2]
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
Number of Subjects Reporting TEAEs:
  At least one TEAE
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  At least one Serious TEAE
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  At least one Severe TEAE
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  No Severe TEAE, but at least one Moderate TEAE
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  No Severe/Moderate TEAEs, but at least one Mild TEAE
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  At least one TEAE Leading to Withdrawal from Study
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  At least one TEAE Leading to Interruption/Discontinuation of 
QWO (CCH-aaes) only
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  At least one TEAE Leading Interruption/Discontinuation of 
Mitigation Treatment only
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  At least one TEAE Leading to Interruption/Discontinuation of 
both QWO (CCH-aaes) and Mitigation Treatment
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  
Number of Subjects with TEAEs Resulting in Death
n 
xx 
xx 
…
xx 
[1] Treatment emergent adverse events (TEAEs) are adverse events with a start date after the first dose of QWO (CCH-aaes). Total 
number of adverse events reported includes the same adverse event occurring multiple times for a subject being counted at each 
occurrence.  Percentages were based on the overall total number of all adverse events within the cohort.
[2] Treatment emergent adverse events (TEAEs) reported as having possibly or probably related to either QWO, or mitigation treatment, 
or both.  Missing relationships were considered as related.
Note: Safety Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment.     
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: please include columns for cohorts 1-3 on page 1, and columns for cohorts 4-6 and Overall on page 2 if it is 
impossible to put all columns in one page. Cohort column headers should read: “Cohort 1 No Mitigation”, “Cohort 2 Compression”, 
“Cohort 3 Cold Packs”, “Cohort 4 Arnica Patches”, “Cohort 5 INhance Serum”, “Cohort 6 PDL Treatment”.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 64
Table 14.3.1.2
Overall Summary of QWO-Related Adverse Events
Safety Population
____________________________________________________________________________________________________________________________________
[1] QWO-related adverse events (QWO-related AEs) are treatment-emergent adverse events reported as having possibly or probably related 
to QWO (CCH-aaes).  Missing relationships were considered as related. Total number of adverse events reported includes the same 
adverse event occurring multiple times for a subject being counted at each occurrence.  Percentages were based on the overall total 
number of all adverse events within the cohort.
Note: Safety Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment.     
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: Use same format as Table 14.3.1.1 with QWO- Related Adverse Events only. Replace TEAE with QWO-Related 
AEs.  Do not include rows “Related to xxx” and “At least 1 AE leading to interruption or discontinuation of xxx”.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 65
Table 14.3.1.3
Overall Summary of Mitigation-Related Adverse Events
Safety Population
____________________________________________________________________________________________________________________________________
[1] Mitigation-related adverse events (Mitigation-related AEs) are treatment-emergent adverse events reported as having possibly or 
probably related to the mitigation treatment. Missing relationships were considered as related. Total number of adverse events 
reported includes the same adverse event occurring multiple times for a subject being counted at each occurrence.  Percentages were 
based on the overall total number of all adverse events within the cohort.
Note: Safety Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment.     
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: Use same format as Table 14.3.1.1 with Mitigation-Related Adverse Events only. Replace TEAE with Mitigation-
Related AEs..  Do not include rows “Related to xxx” and “At least 1 AE leading to interruption or discontinuation of xxx”.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 66
Table 14.3.2.1
Treatment-Emergent Adverse Events by System Organ Class and Preferred Term
Safety Population
System Organ Class
  Preferred Term [1]
Statistic
Cohort 1
No Mitigation
(N=xxx)
Cohort 2
Compression
(N=xxx)
…
Cohort 6
PDL Treatment
(N=xxx)
Number of Subjects with at least one TEAE [2]
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
System Organ Class 1
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  Preferred Term 1
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  Preferred Term 2
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  Preferred Term 3
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
System Organ Class 2
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  Preferred Term 4
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  Preferred Term 5
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  Preferred Term 6
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  Preferred Term 7
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
[1] System organ class and preferred term were coded using MedDRA dictionary (Version xx.x).  If multiple adverse events were reported 
within a given system organ class and/or preferred term, only one event was counted per subject.
[2] Treatment-emergent adverse events (TEAEs) are adverse events with a start date after the first dose of QWO (CCH-aaes).
Note: Safety Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment.     
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: please include columns for cohorts 1-3 on page 1, and columns for cohorts 4-6 and Overall on page 2 if it is 
impossible to put all columns in one page. Cohort column headers should read: “Cohort 1 No Mitigation”, “Cohort 2 Compression”, 
“Cohort 3 Cold Packs”, “Cohort 4 Arnica Patches”, “Cohort 5 INhance Serum”, “Cohort 6 PDL Treatment”.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 67
Table 14.3.2.2
QWO-Related Adverse Events by System Organ Class and Preferred Term
Safety Population
____________________________________________________________________________________________________________________________________
[1] System organ class and preferred term were coded using MedDRA dictionary (Version xx.x).  If multiple adverse events were reported 
within a given system organ class and/or preferred term, only one event was counted per subject.
[2] QWO-related adverse events (QWO-related AEs) are treatment-emergent adverse events reported as having possibly or probably related 
to QWO (CCH-aaes).  Missing relationships were considered as related.
Note: Safety Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment.     
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: Use same format as Table 14.3.2.1 with QWO-Related events only. Replace TEAE with QWO-Related AEs..


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 68
Table 14.3.2.3
Mitigation-Related Adverse Events by System Organ Class and Preferred Term
Safety Population
____________________________________________________________________________________________________________________________________
[1] System organ class and preferred term were coded using MedDRA dictionary (Version xx.x).  If multiple adverse events were reported 
within a given system organ class and/or preferred term, only one event was counted per subject.
[2] Mitigation-related adverse events (Mitigation-related AEs) are treatment-emergent adverse events reported as having possibly or 
probably related to the mitigation treatment. Missing relationships were considered as related.
Note: Safety Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment.     
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: Use same format as Table 14.3.2.1 with Mitigation-Related events only. Replace TEAE with Mitigation-Related 
AEs.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 69
Table 14.3.3.1
Treatment-Emergent Adverse Events by System Organ Class, Preferred Term and Severity
Safety Population
System Organ Class\
  Preferred Term [1]
Severity
Statistic
Cohort 1
No Mitigation
(N=xxx)
Cohort 2
Compression
(N=xxx)
…
Cohort 6
PDL Treatment
(N=xxx)
Number of Subjects whose most severe TEAE [2] is 
Mild
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
Moderate
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
Severe
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
System Organ Class 1
Mild
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
Moderate
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
Severe
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  Preferred Term 1
Mild
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
Moderate
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
Severe
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  Preferred Term 2
Mild
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
Moderate
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
Severe
n (%)
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
[1] System organ class and preferred term were coded using MedDRA dictionary (Version xx.x).  If multiple adverse events were reported 
within a given system organ class and/or preferred term, only the most severe event was counted per subject.
[2] Treatment-emergent adverse events (TEAEs) are adverse events with a start date after the first dose of QWO (CCH-aaes).
Note: Safety Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment.     
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: please include columns for cohorts 1-3 on page 1, and columns for cohorts 4-6 and Overall on page 2 if it is 
impossible to put all columns in one page. Cohort column headers should read: “Cohort 1 No Mitigation”, “Cohort 2 Compression”, 
“Cohort 3 Cold Packs”, “Cohort 4 Arnica Patches”, “Cohort 5 INhance Serum”, “Cohort 6 PDL Treatment”.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 70
Table 14.3.3.2
QWO-Related Adverse Events by System Organ Class, Preferred Term, and Severity
Safety Population
____________________________________________________________________________________________________________________________________
[1] System organ class and preferred term were coded using MedDRA dictionary (Version xx.x).  If multiple adverse events were reported 
within a given system organ class and/or preferred term, only the most severe event was counted per subject.
[2] QWO-related adverse events (QWO-related AEs) are treatment-emergent adverse events reported as having possibly or probably related 
to the QWO (CCH-aaes). Missing relationships were considered as related.
Note: Safety Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment.     
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: Use same format as Table 14.3.2.1 with QWO-Related events only. Replace TEAE with QWO-Related AEs.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 71
Table 14.3.3.3
Mitigation-Related Adverse Events by System Organ Class, Preferred Term, and Severity
Safety Population
____________________________________________________________________________________________________________________________________
[1] System organ class and preferred term were coded using MedDRA dictionary (Version xx.x).  If multiple adverse events were reported 
within a given system organ class and/or preferred term, only the most severe event was counted per subject.
[2] Mitigation-related adverse events (Mitigation-related AEs) are treatment-emergent adverse events reported as having possibly or 
probably related to the mitigation treatment. Missing relationships were considered as related.
Note: Safety Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment.     
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: Use same format as Table 14.3.3.1 with Mitigation-Related events only. Replace TEAE with Mitigation-Related 
AEs.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 72
Table 14.3.4.1
Summary of Serious Adverse Events by Frequency
Safety Population
Cohort 1
No Mitigation
(N=xxx)
…
Cohort 6
PDL Treatment
(N=xxx)
Preferred Term [1]
System Organ Class 
[1]
Subjects
n (%)
Occurrence [3]
n
Any Serious TEAE [2]
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  Most Frequent Preferred Term
System Organ Class
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  2nd Most Frequent Preferred Term
System Organ Class
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  3rd Most Frequent Preferred Term
System Organ Class
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
[1] System organ class and preferred term were coded using MedDRA dictionary (Version xx.x).  If multiple serious adverse events were 
reported within a given system organ class and/or preferred term, only one event was counted per subject.
[2] Serious adverse events (SAEs) were determined by the investigator and marked as SAE on eCRF.
[3] Occurrence is the total number of times the serious adverse event was reported in the study.
Note: Safety Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment.     
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: please include columns for cohorts 1-2 on page 1, columns for cohorts 3-4 on page 2, and columns for cohorts 5-
6 on page 3. Cohort column headers should read: “Cohort 1 No Mitigation”, “Cohort 2 Compression”, “Cohort 3 Cold Packs”, 
“Cohort 4 Arnica Patches”, “Cohort 5 INhance Serum”, “Cohort 6 PDL Treatment”.  


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 73
Table 14.3.5.1
Summary of Most Common (>=5%) Non-Serious Treatment-Emergent Adverse Events by Frequency
Safety Population
Cohort 1
No Mitigation
(N=xxx)
…
Cohort 6
PDL Treatment
(N=xxx)
Preferred Term [1]
System Organ Class 
[1]
Subjects
n (%)
Occurrence [3]
n
Any Most Common Non-Serious TEAE [2]
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  Most Frequent Preferred Term
System Organ Class
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  2nd Most Frequent Preferred Term
System Organ Class
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
  3rd Most Frequent Preferred Term
System Organ Class
xx (xx.x)
xx (xx.x)
…
xx (xx.x)
[1] System organ class and preferred term were coded using MedDRA dictionary (Version xx.x).  If multiple serious adverse events were 
reported within a given system organ class and/or preferred term, only one event was counted per subject.
[2] Any non-serious TEAEs (adverse events with a start date after the first dose of QWO [CCH-aaes]) reported at least 5% of subjects 
in any cohort at least once.
[3] Occurrence is the total number of times the non-serious TEAE was reported in the study.
Note: Safety Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment.     
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: please include columns for cohorts 1-2 on page 1, columns for cohorts 3-4 on page 2, and columns for cohorts 5-
6 on page 3. Cohort column headers should read: “Cohort 1 No Mitigation”, “Cohort 2 Compression”, “Cohort 3 Cold Packs”, 
“Cohort 4 Arnica Patches”, “Cohort 5 INhance Serum”, “Cohort 6 PDL Treatment”.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 74
Table 14.4.1.1
Body Weight (kg) and BMI (kg/m^2)
Safety Population
Parameter
  Timepoint
Statistic
Cohort 1
No Mitigation
(N=xxx)
Cohort 2
Compression
(N=xxx)
...
Cohort 6
PDL Treatment
(N=xxx)
Body Weight (kg)
  Baseline [1]
n
xx
xx
xx
Mean
xx.x
xx.x
…
xx.x
SD
xx.xx
xx.xx
…
xx.xx
Median
xx.x
xx.x
…
xx.x
Min
xx
xx
xx
Max
xx
xx
xx
  Day 71/ET
    Value
n
xx
xx
xx
Mean
xx.x
xx.x
…
xx.x
SD
xx.xx
xx.xx
…
xx.xx
Median
xx.x
xx.x
…
xx.x
Min
xx
xx
xx
Max
xx
xx
xx
    Change from Baseline
n
xx
xx
xx
Mean
xx.x
xx.x
…
xx.x
SD
xx.xx
xx.xx
…
xx.xx
Median
xx.x
xx.x
…
xx.x
Min
xx
xx
xx
Max
xx
xx
xx
BMI (kg/m^2)
  Baseline [1]
n
xx
xx
…
xx
Mean
xx.x
xx.x
…
xx.x
SD
xx.xx
xx.xx
…
xx.xx
Median
xx.x
xx.x
…
xx.x
Min
xx
xx
xx
Max
xx
xx
xx
…
…
…
…
…
…
[1] Based on the last evaluable measurement before first QWO (CCH-aaes) injection at the Baseline Visit (Day 1).
Note: BMI = Body Mass Index; ET = Early Termination.
Safety Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment.     
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 75
Table 14.4.1.1
Body Weight (kg) and BMI (kg/m^2)
Safety Population
Parameter
  Timepoint
Statistic
Cohort 1
No Mitigation
(N=xxx)
Cohort 2
Compression
(N=xxx)
...
Cohort 6
PDL Treatment
(N=xxx)
Programming note: please include columns for cohorts 1-3 on page 1, columns for cohorts 4-6 on page 2 if it is impossible to put all 
columns in one page.   Repeat for BMI Day 71/ET Value and Change from Baseline.  Cohort column headers should read: “Cohort 1 
No Mitigation”, “Cohort 2 Compression”, “Cohort 3 Cold Packs”, “Cohort 4 Arnica Patches”, “Cohort 5 INhance Serum”, 
“Cohort 6 PDL Treatment”.  


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 76
Table 14.4.2.1
Vital Signs: Systolic Blood Pressure (mmHg)
Safety Population
Timepoint
Statistic
Cohort 1
No Mitigation
(N=xxx)
Cohort 2
Compression
(N=xxx)
...
Cohort 6
PDL Treatment
(N=xxx)
Baseline [1]
n
xx
Xx
xx
Mean
xx.x
xx.x
…
xx.x
SD
xx.xx
xx.xx
…
xx.xx
Median
xx.x
xx.x
…
xx.x
Min
xx
Xx
xx
Max
xx
Xx
xx
30 Minutes After Injection
  Value
n
xx
Xx
xx
Mean
xx.x
xx.x
…
xx.x
SD
xx.xx
xx.xx
…
xx.xx
Median
xx.x
xx.x
…
xx.x
Min
xx
Xx
xx
Max
xx
Xx
xx
  Change from Baseline
n
xx
Xx
xx
Mean
xx.x
xx.x
…
xx.x
SD
xx.xx
xx.xx
…
xx.xx
Median
xx.x
xx.x
…
xx.x
Min
xx
Xx
xx
Max
xx
Xx
xx
[1] Based on the last evaluable measurement before first QWO (CCH-aaes) injection at the Baseline Visit (Day 1).
Notes: ET = Early Termination. 
Safety Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment.     
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: please include columns for cohorts 1-3 on page 1, columns for cohorts 4-6 on page 2 if it is impossible to put all 
columns in one page.   Cohort column headers should read: “Cohort 1 No Mitigation”, “Cohort 2 Compression”, “Cohort 3 Cold 
Packs”, “Cohort 4 Arnica Patches”, “Cohort 5 INhance Serum”, “Cohort 6 PDL Treatment”.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 77
Table 14.4.2.2
Vital Signs: Diastolic Blood Pressure (mmHg)
Safety Population
[1] Based on the last evaluable measurement before first QWO (CCH-aaes) injection at the Baseline Visit (Day 1).
Notes: ET = Early Termination. 
Safety Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment.     
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programming note: Use same format as Table 14.4.2.1. Replace Systolic BP with Diastolic BP.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 78
Repeat Table 14.4.2.1 format for the following tables:
Table 14.4.2.3
Vital Signs: Body Temperature (oC)
Safety Population
Table 14.4.2.4
Vital Signs: Pulse Rate (beats per minute)
Safety Population


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 79
Listing 16.2.1.1
Subject Visits and Disposition
Subject ID
Cohort [1]
Visit
Visit Date 
(Study Day [2])
Visit 
Done?/If 
no, Reason
Visit Type
Completed 
Study?
Reason for Early 
Termination/Withdrawal
XXXX-XXXX
Cohort 1
Screening
yyyy-mm-dd (-xx)
Yes
Remote
Day 1
yyyy-mm-dd (xx)
Yes
Remote
Day 2
yyyy-mm-dd (xx)
No/xxxx
Remote
Day 4
yyyy-mm-dd (xx)
Yes
Remote
…
…
…
…
…
…
Day 43
yyyy-mm-dd (xx)
Yes
Remote
No
Pregnancy (xxxx)
Unscheduled 
(if any)
yyyy-mm-dd (xx)
Yes
In-Person
XXXX-XXXX
Cohort 2
Screening
yyyy-mm-dd (-xx)
Yes
Day 1
yyyy-mm-dd (xx)
Yes
Day 2
yyyy-mm-dd (xx)
Yes
Day 4
yyyy-mm-dd (xx)
Yes
…
…
…
…
…
…
Day 71/ET
yyyy-mm-dd (xx)
Yes
Yes
[1] Cohort 1 = No mitigation treatment; Cohort 2 = Compression garment on both buttocks; Cohort 3 = Instant cold packs on right 
buttock only; Cohort 4 = Arnica patches on right buttock only; Cohort 5 = INhance post-injection serum with TreHex technology on right 
buttock only; Cohort 6 = pulse dye laser treatment on right buttock only.
[2] Study day is relative to the day of first QWO (CCH-aaes) injection (i.e. Date of Day 1). 
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 80
Listing 16.2.1.2
Discontinued Subjects 
All Subjects
Subject ID
Cohort [1]
First Injection 
Date
Last Visit Date 
Time in Study 
(days)[2]
Reason for Early 
Termination/Withdrawal
XXXX-XXXX
Cohort 1
yyyy-mm-dd 
yyyy-mm-dd 
xx
xxxxxxxxxxxxxxxxxx
XXXX-XXXX
Cohort 1
yyyy-mm-dd 
yyyy-mm-dd 
xx
Xxxxxxxxxxxxxxxxxx
XXXX-XXXX
Cohort 2
yyyy-mm-dd 
yyyy-mm-dd 
xx
xxxxxxxxxxxxxxxxxx
XXXX-XXXX
Cohort 4
yyyy-mm-dd 
yyyy-mm-dd 
xx
xxxxxxxxxxxxxxxxxx
…
…
…
…
…
…
[1] Cohort 1 = No mitigation treatment; Cohort 2 = Compression garment on both buttocks; Cohort 3 = Instant cold packs on right 
buttock only; Cohort 4 = Arnica patches on right buttock only; Cohort 5 = INhance post-injection serum with TreHex technology on right 
buttock only; Cohort 6 = pulse dye laser treatment on right buttock only.
[2] Time in Study (days) = (Last Visit Date) – (First Injection Date) + 1.
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programmer’s Note: Keep only discontinued subjects who are not screen failures.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 81
Listing 16.2.1.3
Screen Failures
All Subjects
Subject ID
Cohort [1]
Screening Type
Screen Failure Date
Reason for Screen Failure
Specify
XXXX-XXXX
Cohort 1
Initial
yyyy-mm-dd
xxxxxxxxxxxxxxxxxx
xxxxxxxxx
XXXX-XXXX
Cohort 1
Initial
yyyy-mm-dd 
Xxxxxxxxxxxxxxxxxx
Xxxxxxxxx
XXXX-XXXX
Cohort 2
Initial
yyyy-mm-dd
xxxxxxxxxxxxxxxxxx
xxxxxxxxx
XXXX-XXXX
Cohort 4
Rescreening
yyyy-mm-dd
xxxxxxxxxxxxxxxxxx
xxxxxxxxx
…
…
…
…
…
…
[1] Cohort 1 = No mitigation treatment; Cohort 2 = Compression garment on both buttocks; Cohort 3 = Instant cold packs on right 
buttock only; Cohort 4 = Arnica patches on right buttock only; Cohort 5 = INhance post-injection serum with TreHex technology on right 
buttock only; Cohort 6 = pulse dye laser treatment on right buttock only.
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programmer’s Note: sort by subject ID.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 82
Listing 16.2.1.4
Inclusion/Exclusion Criteria
All Subjects
Subject ID
Cohort [1]
Inclusion Criteria Not Met/ 
Exclusion Criteria Met
Inclusion/Exclusion Criterion
XXXX-XXXX
Cohort 1
INC01
xxxxxxxxxxxxxxxxxx
XXXX-XXXX
Cohort 1
EXCL02
Xxxxxxxxxxxxxxxxxx
XXXX-XXXX
Cohort 2
xxxxx
xxxxxxxxxxxxxxxxxx
XXXX-XXXX
Cohort 4
xxxxx
xxxxxxxxxxxxxxxxxx
…
…
…
…
[1] Cohort 1 = No mitigation treatment; Cohort 2 = Compression garment on both buttocks; Cohort 3 = Instant cold packs on right 
buttock only; Cohort 4 = Arnica patches on right buttock only; Cohort 5 = INhance post-injection serum with TreHex technology on right 
buttock only; Cohort 6 = pulse dye laser treatment on right buttock only.
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programmer’s Note: sort by subject ID.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 83
Listing 16.2.2
Protocol Deviations 
All Subjects
Subject ID
Cohort [1]
Date of Deviation 
(Study Day [2])
Protocol Deviation 
Number/Category
Description of Protocol Deviation
Severity of 
Protocol Deviation
XXXX-XXXX
Cohort 1
yyyy-mm-dd (-xx)
xx/xxxxxxxxx
xxxxxxxxxxxxxxxxxx
Major
XXXX-XXXX
Cohort 1
yyyy-mm-dd (xx) 
xx/xxxxxxxxx
Xxxxxxxxxxxxxxxxxx
Minor
XXXX-XXXX
Cohort 2
yyyy-mm-dd (-xx)
xx/xxxxxxxxx
xxxxxxxxxxxxxxxxxx
xxxxxxxxx
XXXX-XXXX
Cohort 4
yyyy-mm-dd (xx)
xx/xxxxxxxxx
xxxxxxxxxxxxxxxxxx
xxxxxxxxx
…
…
…
…
…
…
[1] Cohort 1 = No mitigation treatment; Cohort 2 = Compression garment on both buttocks; Cohort 3 = Instant cold packs on right 
buttock only; Cohort 4 = Arnica patches on right buttock only; Cohort 5 = INhance post-injection serum with TreHex technology on right 
buttock only; Cohort 6 = pulse dye laser treatment on right buttock only.
[2] Study day is relative to the day of first QWO (CCH-aaes) injection (i.e. Date of Day 1).
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programmer’s Note: sort by subject ID.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 84
Listing 16.2.3
Exclusion from Analysis Population
All Enrolled Subjects
Subject ID
Cohort [1]
Population from Which 
Subject was Excluded [2]
Reason for Exclusion
XXXX-XXXX
Cohort 1
Evaluable
xxxxxxxxx
XXXX-XXXX
Cohort 1
Evaluable
xxxxxxxxx
XXXX-XXXX
Cohort 2
Safety
xxxxxxxxx
XXXX-XXXX
Cohort 4
Evaluable
xxxxxxxxx
…
…
…
…
[1] Cohort 1 = No mitigation treatment; Cohort 2 = Compression garment on both buttocks; Cohort 3 = Instant cold packs on right 
buttock only; Cohort 4 = Arnica patches on right buttock only; Cohort 5 = INhance post-injection serum with TreHex technology on right 
buttock only; Cohort 6 = pulse dye laser treatment on right buttock only.
[2] Safety Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without mitigation 
treatment.  Evaluable Population includes all enrolled subjects who received at least 1 injection of QWO (CCH-aaes) with or without 
mitigation treatment and have at least one bruising assessment after the first dose of QWO (CCH-aaes).   
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programmer’s Note: sort by subject ID.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 85
Listing 16.2.4.1
Demographics 
All Enrolled Subjects
Subject ID
Cohort [1]
Age 
(yrs)
Sex
Race 
(Specify)
Ethnicity
Fitzpatrick 
Skin Scale 
[2]
Child-
bearing 
Potential? 
[3] 
Date of 
Last 
Menstrual 
Period
Reason Cannot 
Bear Children 
(Specify)
XXXX-XXXX
Cohort 1
xx
Female
White
Hispanic
I
Yes
yyyy-mm-dd
XXXX-XXXX
Cohort 1
xx
Female
Black
Not Hispanic
II
Yes
yyyy-mm-dd
XXXX-XXXX
Cohort 2
xx
Female
Other(xxx)
xxxxxxxx
I
No
Other(xxxxxx)
XXXX-XXXX
Cohort 4
xx
Female
xxxxxxxxx
xxxxxxxx
III
Yes
yyyy-mm-dd
…
…
…
…
…
…
…
…
…
…
[1] Cohort 1 = No mitigation treatment; Cohort 2 = Compression garment on both buttocks; Cohort 3 = Instant cold packs on right 
buttock only; Cohort 4 = Arnica patches on right buttock only; Cohort 5 = INhance post-injection serum with TreHex technology on right 
buttock only; Cohort 6 = pulse dye laser treatment on right buttock only.
[2] Fitzpatrick Scale: I: Pale white skin, blue/hazel eyes, blond/red hair; II: Fair skin, blue eyes; III: Darker white skin; IV: 
Light brown skin; V: Brown skin; VI: Dark brown or black skin. Only subjects with a Fitzpatrick skin rating of I-III at the Screening 
Visit were eligible for the study per the protocol inclusion criteria.  
[3] If yes, date of last menstrual period was collected.  If no, reason cannot bear children was collected.
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programmer’s Note: sort by subject ID.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 86
Listing 16.2.4.2
Baseline Characteristics
All Enrolled Subjects
Subject ID
Cohort [1]
Height
(cm)
Weight
(kg)
BMI
(kg/m^2)
Alcohol Use
Tobacco Use
Left/Right 
CR-PCSS Score 
at Screening 
[2]
Left/Right 
Hexsel CSS 
Score at 
Screening [3]
XXXX-XXXX
Cohort 1
xx
xx
xx
No
No
L: 3
R: 3
L: 0
R: 0 
XXXX-XXXX
Cohort 1
xx
xx
xx
No
Current 
L: 3
R: 3
L: xx
R: xx
XXXX-XXXX
Cohort 2
xx
xx
xx
Current
Current
L: 3
R: 3
L: xx
R: xx
XXXX-XXXX
Cohort 4
xx
xx
xx
Former
No
L: 3
R: 3
L: xx
R: xx
…
…
…
…
…
…
…
…
…
[1] Cohort 1 = No mitigation treatment; Cohort 2 = Compression garment on both buttocks; Cohort 3 = Instant cold packs on right 
buttock only; Cohort 4 = Arnica patches on right buttock only; Cohort 5 = INhance post-injection serum with TreHex technology on right 
buttock only; Cohort 6 = pulse dye laser treatment on right buttock only.
[2] CR-PCSS = Clinician-Reported Photonumeric Cellulite Severity Scale. Only subjects with a baseline CR-PCSS rating of 3 (Moderate) 
on each buttock at the Screening Visit were included in the study.
[3] CSS = Cellulite Severity Scale.  Only subjects with a baseline Hexsel CSS Subsection D score of 0 (Absence of flaccidity or 
sagging of skin) or 1 (Slightly draped appearance) on each buttock were included in the study.
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programmer’s Note: sort by subject ID.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 87
Listing 16.2.4.3
Medical and Surgical History
All Enrolled Subjects
Subject ID
Cohort [1]
Term
Start Date
Stop Date
Ongoing?
XXXX-XXXX
Cohort 1
Xxxxxxxxxxxxxx
yyyy-mm-dd
yyyy-mm-dd
No
Xxxxxxxxxxxxxx
yyyy-mm-dd
yyyy-mm-dd
No
XXXX-XXXX
Cohort 2
Xxxxxxxxxxxxxx
yyyy-mm-dd
Yes
Xxxxxxxxxxxxxx
yyyy-mm-dd
yyyy-mm-dd
No
…
…
…
…
…
…
[1] Cohort 1 = No mitigation treatment; Cohort 2 = Compression garment on both buttocks; Cohort 3 = Instant cold packs on right 
buttock only; Cohort 4 = Arnica patches on right buttock only; Cohort 5 = INhance post-injection serum with TreHex technology on right 
buttock only; Cohort 6 = pulse dye laser treatment on right buttock only.
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programmer’s Note: sort by subject ID first and all entries will be sorted by start date within a subject.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 88
Listing 16.2.4.4
Prior and Concomitant Medications
All Enrolled Subjects
Subject ID
Cohort [1]
Prior or 
Concomitant 
[2]
S: System Organ Class
P: Preferred Term
V: Verbatim [3]
Start Date (Study 
Day)/
Stop Date (Study Day) 
[4]
Indication
D: Dose Unit
R: Route
F: Frequency
For AE?
XXXX-XXXX
Cohort 1
Prior
S: xxxxxxxxxxxxxx
P: xxxxxxxxxxxxxx
V: xxxxxxxxxxxxxx
(yyyy-mm-dd (-xx)/
yyyy-mm-dd (xx)
xxxxxxxxxx
D: xx Unit
R: xxxxxx
F: xxxxxx
Yes
Concomitant
S: xxxxxxxxxxxxxx
P: xxxxxxxxxxxxxx
V: xxxxxxxxxxxxxx
yyyy-mm-dd (xx)/
Ongoing
xxxxxxxxxx
D: xx Unit
R: xxxxxx
F: xxxxxx
Yes
XXXX-XXXX
Cohort 2
Prior
S: xxxxxxxxxxxxxx
P: xxxxxxxxxxxxxx
V: xxxxxxxxxxxxxx
yyyy-mm-dd (-xx)/
yyyy-mm-dd (xx)
xxxxxxxxxx
D: xx Unit
R: xxxxxx
F: xxxxxx
No
Concomitant
S: xxxxxxxxxxxxxx
P: xxxxxxxxxxxxxx
V: xxxxxxxxxxxxxx
yyyy-mm-dd (xx)/
Ongoing
xxxxxxxxxx
D: xx Unit
R: xxxxxx
F: xxxxxx
Yes
…
…
…
…
…
[1] Cohort 1 = No mitigation treatment; Cohort 2 = Compression garment on both buttocks; Cohort 3 = Instant cold packs on right 
buttock only; Cohort 4 = Arnica patches on right buttock only; Cohort 5 = INhance post-injection serum with TreHex technology on right 
buttock only; Cohort 6 = pulse dye laser treatment on right buttock only.
[2] Prior medications are any medication reported as taken prior to Day 1. Concomitant medications are any medication reported as 
taken on or after Day 1 (Baseline Visit) through Day 71/Early Termination Visit.    
[3] System organ class and preferred term were coded using MedDRA dictionary (Version xx.x).
[4] Study day is relative to the day of first QWO (CCH-aaes) injection (i.e. Date of Day 1). 
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programmer’s Note: sort by subject ID first and all drugs will be sorted by start date within a subject.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 89
Listing 16.2.4.5
Prior and Concomitant Procedures
All Enrolled Subjects
______________________________________________________________________________________________________________________________________
[1] Cohort 1 = No mitigation treatment; Cohort 2 = Compression garment on both buttocks; Cohort 3 = Instant cold packs on right 
buttock only; Cohort 4 = Arnica patches on right buttock only; Cohort 5 = INhance post-injection serum with TreHex technology on right 
buttock only; Cohort 6 = pulse dye laser treatment on right buttock only.
[2] Prior procedures are any procedure reported as administered prior to Day 1. Concomitant procedures are any procedures reported as 
administered on or after Day 1 (B Visit) through Day 71/Early Termination Visit.    
[3] System organ class and preferred term were coded using MedDRA dictionary (Version xx.x).
[4] Study day is relative to the day of first QWO (CCH-aaes) injection (i.e. Date of Day 1).
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programmer’s Note: sort by subject ID first and all drugs will be sorted by start date within a subject. Use same format as Listing 
16.2.4.4.  Remove column concerning dose/unit/frequency as this is not collected for procedures/therapies.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 90
Listing 16.2.5.1
Treatment Administration: QWO (CCH-aaes)
All Enrolled Subjects
Subject ID
Cohort [1]
Visit
Visit Date 
Visit 
Time
Treatment Area
Number of 
Injections
XXXX-XXXX
Cohort 1
Screening
yyyy-mm-dd
00:00
Left Buttock
xx
Right Buttock
xx
Day 1
yyyy-mm-dd
00:00
Left Buttock
xx
Right Buttock
xx
XXXX-XXXX
Cohort 2
Screening
yyyy-mm-dd
00:00
Left Buttock
xx
Right Buttock
xx
Day 1
yyyy-mm-dd
00:00
Left Buttock
xx
Right Buttock
xx
Day 22
yyyy-mm-dd
00:00
Left Buttock
Xx
…
…
…
…
…
…
…
[1] Cohort 1 = No mitigation treatment; Cohort 2 = Compression garment on both buttocks; Cohort 3 = Instant cold packs on right 
buttock only; Cohort 4 = Arnica patches on right buttock only; Cohort 5 = INhance post-injection serum with TreHex technology on right 
buttock only; Cohort 6 = pulse dye laser treatment on right buttock only.
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programmer’s Note: sort by subject ID first and all entries will be sorted by visit date within a subject.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 91
Listing 16.2.5.2
Treatment Administration: Mitigation Treatment
All Enrolled Subjects
Subject ID
Cohort 
[1]
Visit
Start Date 
(Study Day) 
[2]
End Date 
(Study Day) 
[2]
Mitigation Treatment
Administered Location(s)
XXXX-XXXX
Cohort 2
Day 1
yyyy-mm-dd 
(xx)
yyyy-mm-dd 
(xx)
Compression Garment
Left Buttock, Right Buttock
Day 2
yyyy-mm-dd 
(xx)
yyyy-mm-dd 
(xx)
Compression Garment
Left Buttock, Right Buttock
XXXX-XXXX
Cohort 6
xxxxx
yyyy-mm-dd 
(xx)
yyyy-mm-dd 
(xx)
Pulse Dye Laser Treatment
Right Buttock
xxxxx
yyyy-mm-dd 
(xx)
yyyy-mm-dd 
(xx)
Pulse Dye Laser Treatment
Right Buttock
Xxxxx
yyyy-mm-dd 
(xx)
yyyy-mm-dd 
(xx)
Pulse Dye Laser Treatment
Right Buttock
…
…
…
…
…
[1] Cohort 1 = No mitigation treatment; Cohort 2 = Compression garment on both buttocks; Cohort 3 = Instant cold packs on right 
buttock only; Cohort 4 = Arnica patches on right buttock only; Cohort 5 = INhance post-injection serum with TreHex technology on right 
buttock only; Cohort 6 = pulse dye laser treatment on right buttock only.
[2] Study day is relative to the day of first QWO (CCH-aaes) injection (i.e. Date of Day 1).
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programmer’s Note: sort by subject ID first and all entries will be sorted by visit date within a subject.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 92
Listing 16.2.6.1
Investigator Assessment of Bruising Severity
All Enrolled Subjects
Subject ID
Cohort [1]
Visit
Assessment Date
Assessment Complete? 
If no, Reason
Treatment Area
Bruising Severity Rating [2]
XXXX-XXXX
Cohort 1
Day 1
yyyy-mm-dd
Yes
Left Buttock
4 (Very severe bruising)
Right Buttock
2 (Moderate bruising)
Day 2
yyyy-mm-dd
Yes
Left Buttock
xxxxxxxxx
Right Buttock
Xxxxxxxxx
XXXX-XXXX
Cohort 2
Day 1
yyyy-mm-dd
No(xxxxxxxxxx)
Day 2
yyyy-mm-dd
xxxx
Left Buttock
xxxxxxxxx
Right Buttock
Xxxxxxxxx
Day 4
yyyy-mm-dd
xxxx
Left Buttock
xxxxxxxxx
…
…
…
…
…
…
[1] Cohort 1 = No mitigation treatment; Cohort 2 = Compression garment on both buttocks; Cohort 3 = Instant cold packs on right 
buttock only; Cohort 4 = Arnica patches on right buttock only; Cohort 5 = INhance post-injection serum with TreHex technology on right 
buttock only; Cohort 6 = pulse dye laser treatment on right buttock only.
[2] Bruising severity rating was based on the following scale: 0 (None or almost no bruising), 1 (Mild bruising), 2 (Moderate
bruising), 3 (Severe bruising), 4 (Very severe bruising). 
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programmer’s Note: sort by subject ID first and all entries will be sorted by assessment date within a subject.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 93
Listing 16.2.6.2
Investigator Global Aesthetic Improvement Scale (I-GAIS) Assessment
All Enrolled Subjects
Subject ID
Cohort [1]
Visit
Assessment Date
Assessment Complete? 
If no, Reason
Treatment Area
I-GAIS Rating [2]
XXXX-XXXX
Cohort 1
Day 22
yyyy-mm-dd
Yes
Left Buttock
+3 (Very much improved)
Right Buttock
+2 (Much improved)
Day 43
yyyy-mm-dd
Yes
Left Buttock
xxxxxxxxx
Right Buttock
Xxxxxxxxx
XXXX-XXXX
Cohort 2
Day 22
yyyy-mm-dd
No(xxxxxxxxxx)
Day 43
yyyy-mm-dd
xxxx
Left Buttock
xxxxxxxxx
Right Buttock
Xxxxxxxxx
Day 71
yyyy-mm-dd
xxxx
Left Buttock
xxxxxxxxx
…
…
…
…
…
…
[1] Cohort 1 = No mitigation treatment; Cohort 2 = Compression garment on both buttocks; Cohort 3 = Instant cold packs on right 
buttock only; Cohort 4 = Arnica patches on right buttock only; Cohort 5 = INhance post-injection serum with TreHex technology on right 
buttock only; Cohort 6 = pulse dye laser treatment on right buttock only.
[2] I-GAIS rating was based on the following scale: +3 (Very much improved), +2 (Much improved), +1 (Improved), 0 (No change), -1
(Worse), -2 (Much worse), -3 (Very much worse)
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programmer’s Note: sort by subject ID first and all entries will be sorted by assessment date within a subject.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 94
Listing 16.2.6.3
Investigator Bruising Improvement Scale (I-BIS) Assessment
All Enrolled Subjects
Subject ID
Cohort [1]
Visit
Assessment Date
Assessment Complete? If no, 
Reason
I-BIS Rating [2]
XXXX-XXXX
Cohort 3
Day 2
yyyy-mm-dd
Yes
1 (Worse – more bruising)
Day 4
yyyy-mm-dd
Yes
2 (Similar)
XXXX-XXXX
Cohort 4
Day 2
yyyy-mm-dd
Yes
xxxxxxxxx
Day 4
yyyy-mm-dd
No(xxxxxxxxxx)
xxxxxxxxx
Day 7
yyyy-mm-dd
xxxx
xxxxxxxxx
…
…
…
…
…
…
[1] Cohort 1 = No mitigation treatment; Cohort 2 = Compression garment on both buttocks; Cohort 3 = Instant cold packs on right 
buttock only; Cohort 4 = Arnica patches on right buttock only; Cohort 5 = INhance post-injection serum with TreHex technology on right 
buttock only; Cohort 6 = pulse dye laser treatment on right buttock only.
[2] I-BIS rating was based on the following scale: 1 (Worse – more bruising), 2 (Similar), 3 (Improved – less bruising).  I-BIS Rating 
is directly obtained from the investigator’s assessment rating comparing the bruising of the mitigation-treated buttock to the 
untreated (with mitigation treatment) buttock.  The I-BIS assessment was not completed for subjects that did not receive mitigation 
treatment (Cohort 1) or subjects that received bilateral mitigation treatment (Cohort 2), as these subjects did not have an 
untreated buttock as a comparator.
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programmer’s Note: sort by subject ID first and all entries will be sorted by assessment date within a subject.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 95
Listing 16.2.6.4
Subject Bruising Improvement Scale (S-BIS) Assessment
All Enrolled Subjects
_________________________________________________________________________________________________________________________________
[1] Cohort 1 = No mitigation treatment; Cohort 2 = Compression garment on both buttocks; Cohort 3 = Instant cold packs on right 
buttock only; Cohort 4 = Arnica patches on right buttock only; Cohort 5 = INhance post-injection serum with TreHex technology on right 
buttock only; Cohort 6 = pulse dye laser treatment on right buttock only.
[2] S-BIS rating was based on the following scale: 1 (Worse – more bruising), 2 (Similar), 3 (Improved – less bruising).  S-BIS Rating 
is directly obtained from the subject’s assessment rating comparing the bruising of the mitigation-treated buttock to the untreated 
(with mitigation treatment) buttock.  The S-BIS assessment was not completed in subjects that did not receive mitigation treatment 
(Cohort 1) or subjects that received bilateral mitigation treatment (Cohort 2), as these subjects did not have an untreated buttock as 
a comparator. 
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programmer’s Note: sort by subject ID first and all entries will be sorted by assessment date within a subject.  Use same format as 
Listing 16.2.6.3.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 96
Listing 16.2.6.5
Patient Bother by Bruising Assessment
All Enrolled Subjects
Subject ID
Cohort [1]
Visit
Assessment Date
Assessment Complete? 
If no, Reason
Treatment Area
Patient Bother by Bruising 
Rating [2]
XXXX-XXXX
Cohort 1
Day 22
yyyy-mm-dd
Yes
Left Buttock
3 (Moderately bothered)
Right Buttock
1 (Not at all bothered)
Day 43
yyyy-mm-dd
Yes
Left Buttock
xxxxxxxxx
Right Buttock
Xxxxxxxxx
XXXX-XXXX
Cohort 2
Day 22
yyyy-mm-dd
No(xxxxxxxxxx)
Day 43
yyyy-mm-dd
xxxx
Left Buttock
xxxxxxxxx
Right Buttock
Xxxxxxxxx
Day 71
yyyy-mm-dd
xxxx
Left Buttock
xxxxxxxxx
…
…
…
…
…
…
[1] Cohort 1 = No mitigation treatment; Cohort 2 = Compression garment on both buttocks; Cohort 3 = Instant cold packs on right 
buttock only; Cohort 4 = Arnica patches on right buttock only; Cohort 5 = INhance post-injection serum with TreHex technology on right 
buttock only; Cohort 6 = pulse dye laser treatment on right buttock only.
[2] Patient bothered by bruising rating was based on the following scale: 1 (Not at all bothered), 2 (A little bothered), 3 
(Moderately bothered), 4 (Extremely bothered).
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programmer’s Note: sort by subject ID first and all entries will be sorted by assessment date within a subject.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 97
Programmer’s Note: sort by subject ID first and all entries will be sorted by assessment date within a subject.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 98
Listing 16.2.6.7
Digital Photography
All Enrolled Subjects
Subject ID
Cohort [1]
Visit
Assessment 
Date
Timepoint [2]
Photos Taken? If no, Reason
XXXX-XXXX
Cohort 1
Day 1
yyyy-mm-dd
Before marking dimples and 
injection sites
Yes
Day 2
yyyy-mm-dd
N/A
Yes
XXXX-XXXX
Cohort 2
Day 1
yyyy-mm-dd
xxxxxxxxxxxx
No(xxxxxxxxxx)
Day 2
yyyy-mm-dd
xxxxxxxxxxxx
xxxx
…
…
…
…
[1] Cohort 1 = No mitigation treatment; Cohort 2 = Compression garment on both buttocks; Cohort 3 = Instant cold packs on right 
buttock only; Cohort 4 = Arnica patches on right buttock only; Cohort 5 = INhance post-injection serum with TreHex technology on right 
buttock only; Cohort 6 = pulse dye laser treatment on right buttock only.
[2] Timepoint = N/A: no dimple or injection site markings were made at this visit; only 1 set of photos was required.
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programmer’s Note: sort by subject ID first and all entries will be sorted by assessment date within a subject.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 99
Listing 16.2.7.1
Adverse Events
All Enrolled Subjects
Subject ID
Cohort [1]
S: System Organ Class
P: Preferred Term
V: Verbatim [2]
Start Date (Study 
Day)/ Stop Date 
(Study Day)/ 
Duration [3] 
T: TEAE?
I: Injection 
Site Reaction? 
S: SAE? [4]
S: Severity
T: Treatment 
O: Outcome
Relation to QWO/ 
Action Taken
Relation to 
Mitigation 
Treatment/ 
Action Taken
XXXX-XXXX
Cohort 1
S: xxxxxxxxxxxxxx
P: xxxxxxxxxxxxxx
V: xxxxxxxxxxxxxx
yyyy-mm-dd (-xx)/
yyyy-mm-dd (xx)/
xx
T: Yes
I: No
S: No
S: Mild
T: None
O: Recovered/ 
Resolved
Not Related/ 
Not Changed
Not Related/ 
Not Changed
S: xxxxxxxxxxxxxx
P: xxxxxxxxxxxxxx
V: xxxxxxxxxxxxxx
yyyy-mm-dd (xx)/
Ongoing 
T: Yes
I: No
S: No
S: Moderate
T: Medication
O: Recovered/ 
Resolved
Probable/ 
Withdrawn
Not Related/ 
Not Changed
XXXX-XXXX
Cohort 2
S: xxxxxxxxxxxxxx
P: xxxxxxxxxxxxxx
V: xxxxxxxxxxxxxx
yyyy-mm-dd (-xx)/
yyyy-mm-dd (xx)/ 
xx
T: Yes
I: No
S: No
S: xxx
T: xxxx
O: xxxx
xxxxx/xxxxx
xxxxx/xxxxx
S: xxxxxxxxxxxxxx
P: xxxxxxxxxxxxxx
V: xxxxxxxxxxxxxx
yyyy-mm-dd (xx)/
Ongoing
T: Yes
I: No
S: No
S: xxxx
T: xxxx
O: xxxx
xxxxx/xxxxx
xxxxx/xxxxx
…
…
…
…
…
…
…
…
[1] Cohort 1 = No mitigation treatment; Cohort 2 = Compression garment on both buttocks; Cohort 3 = Instant cold packs on right 
buttock only; Cohort 4 = Arnica patches on right buttock only; Cohort 5 = INhance post-injection serum with TreHex technology on right 
buttock only; Cohort 6 = pulse dye laser treatment on right buttock only.
[2] System organ class and preferred term were coded using MedDRA dictionary (Version xx.x).
[3] Study day is relative to the day of first QWO (CCH-aaes) injection (i.e. Date of Day 1). Duration = (Stop Date) – (Start Date) + 
1. 
[4] TEAE = treatment-emergent adverse event; SAE = serious adverse event.
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programmer’s Note: sort by subject ID first and all AEs will be sorted by start date within a subject.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 100
Repeat Listing 16.2.7.1 for the following listings:
Listing 16.2.7.2
Deaths
All Enrolled Subjects
Programmer’s note: Include only death events.
Listing 16.2.7.3
Non-fatal Serious Adverse Events
All Enrolled Subjects
Programmer’s note: Include only non-fatal serious adverse events.
Listing 16.2.7.4
Non-serious AEs Leading to either QWO or Mitigation Treatment Interruption or Discontinuation
All Enrolled Subjects
Programmer’s note: Include only AEs where either QWO Action Taken or Mitigation Action Taken = Interrupted.
Listing 16.2.7.5
Non-serious AEs Leading to either QWO or Mitigation Treatment Withdrawn
All Enrolled Subjects
Programmer’s note: Include only AEs where either QWO Action Taken or Mitigation Action Taken = Withdrawn.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 101
Listing 16.2.8.1
Vital Signs
All Enrolled Subjects
Subject ID
Cohort [1]
Visit
Timepoint [2]
Assessment 
Date 
Assessment 
Time
Assessment 
Complete? If 
no, Reason
Systolic
BP
(mmHg)
Diastolic
BP
(mmHg)
Pulse 
Rate
(bpm)
Temp
(oC)
XXXX-XXXX
Cohort 1
Screening
N/A
yyyy-mm-dd 
00:00
Yes
xx
xx
xx
xx
Day 1
Pre-injection
Yes
xx
xx
xx
xx
15 minutes
yyyy-mm-dd 
00:00
No(xxxxxxxxxx)
30 minutes
yyyy-mm-dd 
00:00
xxxx
Xx
Xx
Xx
Xx
yyyy-mm-dd 
00:00
XXXX-XXXX
Cohort 2
xxxxxx
xxxxxx
…
…
xxxx
xx
xx
xx
xx
xxxxxx
xxxxxx
xxxx
xx
xx
xx
xx
xxxxxx
xxxxxx
xxxx
xx
xx
xx
xx
…
…
…
…
…
…
…
…
…
[1] Cohort 1 = No mitigation treatment; Cohort 2 = Compression garment on both buttocks; Cohort 3 = Instant cold packs on right 
buttock only; Cohort 4 = Arnica patches on right buttock only; Cohort 5 = INhance post-injection serum with TreHex technology on right 
buttock only; Cohort 6 = pulse dye laser treatment on right buttock only.
[2] Timepoint = N/A: no injections were administered at this visit; only 1 set of vital measurements were collected.
Note: BP = blood pressure; bpm = beats per minute.
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programmer’s Note: sort by subject ID first and all entries will be sorted by assessment date within a subject.


Statistical Analysis Plan (SAP) Module 2 – Study EN3835-401 MOBI
10-Feb-2021
Endo Pharmaceuticals Inc.
Page 102
Listing 16.2.8.2
Physical Examinations
All Enrolled Subjects
Subject ID
Cohort [1]
Visit
Assessment 
Date 
Assessment 
Time
Assessment 
Complete? If 
no, Reason
Body System
Finding
Specify (if 
Abnormal)
XXXX-XXXX
Cohort 1
Screening
yyyy-mm-dd 
00:00
Yes
Lungs
Normal
Day 1
No(xxxxxxxxxx)
Day 2
yyyy-mm-dd 
00:00
xxxx
Heart
Abnormal
xxxxxxxxx
XXXX-XXXX
Cohort 2
xxxxxx
yyyy-mm-dd 
00:00
xxxx
Other(xxxxx)
Abnormal
xxxxxxxxx
xxxxxx
yyyy-mm-dd 
00:00
xxxx
xxxxx
xxxxxx
xxxxxx
yyyy-mm-dd 
00:00
xxxx
xxxxx
xxxxxx
…
…
…
…
…
…
…
…
…
[1] Cohort 1 = No mitigation treatment; Cohort 2 = Compression garment on both buttocks; Cohort 3 = Instant cold packs on right 
buttock only; Cohort 4 = Arnica patches on right buttock only; Cohort 5 = INhance post-injection serum with TreHex technology on right 
buttock only; Cohort 6 = pulse dye laser treatment on right buttock only.
Datasets (extraction):  status(ddmmmyyyy),
ddmmmmyyyy:HHMM
Source:  ...\xxxxxxx.sas
Programmer’s Note: sort by subject ID first and all entries will be sorted by assessment date within a subject.


Signature Manifest
Document Number: RDM-CLIN-DOC-02000
Revision: 1
Title: EN3835-401 Statistical Analysis Plan - Module 1
All dates and times are in Eastern Time.
EN3835-401 SAP approval
RDM Approval Step
Name/Signature
Title
Date
Meaning/Reason
11 Feb 2021, 04:52:38 PM
Approved
11 Feb 2021, 06:43:06 PM
Approved
12 Feb 2021, 12:36:23 PM
Approved
12 Feb 2021, 02:26:24 PM
Approved
12 Feb 2021, 02:39:16 PM
Approved
14 Feb 2021, 04:55:07 PM
Approved
Page 1 of 1
Signature Manifest
2/15/2021
file:///D:/MasterControl/Publishing/installedServices/publishingKSLE/adlib/work/mcjobs/all/D1C...