APHRODITE-1: A Phase 2, Open Label, Self-Controlled Study of Different Interventions to Reduce Bruising Following CCH-Aaes Treatment for Cellulite of the Buttocks in Adult Females
Phase: PHASE2
Conditions: Edematous Fibrosclerotic Panniculopathy, Cellulite
Sponsor: Endo Pharmaceuticals

Protocol 
 
 
Endo Pharmaceuticals Inc. 
1400 Atwater Drive  
Malvern, PA 19355 USA 
EN3835-226 CEL 
APHRODITE-1: A PHASE 2, OPEN-LABEL, SELF-
CONTROLLED STUDY OF DIFFERENT 
INTERVENTIONS TO REDUCE BRUISING 
FOLLOWING CCH-AAES TREATMENT FOR 
CELLULITE OF THE BUTTOCKS 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 
Date: 
Original Protocol: 31 March 2022 
Amendment 01: 13 May 2022 
Amendment 02: 12 August 2022 
The sponsor of the IND is Endo Global Aesthetics Limited (EGAL); however, Endo 
Pharmaceuticals Inc. (Endo) is authorized to act and to communicate on behalf of EGAL. The 
sponsor is responsible for the conduct of the study, analysis of the data, and preparation of the 
clinical study report. 
NCT #: NCT05419505

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6. 
SELECTION AND WITHDRAWAL OF PARTICIPANTS .....................................47 
6.1. 
Participant Inclusion Criteria ......................................................................................47 
6.2. 
Participant Exclusion Criteria .....................................................................................48 
6.3. 
Lifestyle Considerations .............................................................................................50 
6.4. 
Screen Failures ............................................................................................................51 
7. 
STUDY INTERVENTION ........................................................................................51 
7.1. 
Selection and Marking of Dimples .............................................................................51 
7.2. 
Treatment Administration ...........................................................................................52 
7.2.1. 
QWO (CCH-aaes) .......................................................................................................52 
7.2.2. 
Cohorts 1-5, Control Sides, QWO (CCH-aaes) – Labeled Dose and 
Concentration ..............................................................................................................54 
7.2.3. 
Cohort 1, Investigational Side Only, QWO (CCH-aaes) – Half-dose of 
Labeled Concentration ................................................................................................55 
7.2.4. 
Cohort 2, Investigational Side Only, QWO (CCH-aaes) – Labeled Dose 
~5-fold Diluted Concentration ....................................................................................55 
7.2.5. 
Cohort 3, Investigational Side Only, QWO (CCH-aaes) – Labeled Dose and 
Concentration at ¼-inch Depth ...................................................................................55 
7.2.6. 
Cohort 4, Investigational Side Only, QWO (CCH-aaes) – Labeled Dose 
~2.5-fold Diluted Concentration at ¼-inch Injection Depth .......................................55 
7.2.7. 
Cohort 5, Investigational Side Only, QWO (CCH-aaes) – Half-dose at a 
Labeled Concentration with Lidocaine 2% and Epinephrine 1:200, 000 as a 
Diluent Additive .........................................................................................................56 
7.2.8. 
Cohort 6, Investigational Side Only, QWO (CCH-aaes) – Quarter-dose with 
One-Half Concentration and Two Treatment Sessions at Approximately 42 
Days Between Visits ...................................................................................................56 
7.2.9. 
Cohort 6, Control Side Only, QWO (CCH-aaes) – Half of the Labeled Dose 
(0.42 mg/control side) Using the Labeled Concentration (0.23 mg/mL) at 
Approximately 42 Days between Visits .....................................................................56 
7.2.10. 
Cohort 7, Labeled Dose and Concentration of QWO (CCH-aaes) with 
Tranexamic Acid ........................................................................................................56 
7.2.11. 
Care Procedures After Injection .................................................................................57 
7.2.12. 
Preparation/Handling/Storage/Accountability ............................................................57 
7.3. 
Measures to Minimize Bias ........................................................................................58 
7.3.1. 
Interactive Response Technology ...............................................................................58 
7.4. 
Study Intervention Compliance ..................................................................................58 
7.5. 
Prior and Concomitant Medications and Procedures ..................................................59 

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7.5.1. 
Prohibited Medications/ Procedures ...........................................................................59 
7.5.2. 
Suggested Concomitant Medications and Procedures ................................................60 
7.5.3. 
COVID-19 Related Protocol Deviations ....................................................................60 
8. 
DISCONTINUATION FROM STUDY INTERVENTION AND STUDY 
WITHDRAWAL ........................................................................................................60 
8.1. 
Discontinuation of Study Intervention ........................................................................60 
8.2. 
Participant Withdrawal from the Study ......................................................................60 
8.3. 
Lost to Follow-up .......................................................................................................61 
9. 
STUDY ASSESSMENTS AND PROCEDURES......................................................61 
9.1. 
Screening Assessments ...............................................................................................62 
9.1.1. 
Medical and Surgical History .....................................................................................62 
9.1.2. 
Physical Examination .................................................................................................62 
9.1.3. 
Fitzpatrick Skin Scale .................................................................................................62 
9.1.4. 
Hexsel Cellulite Scale Severity ..................................................................................62 
9.1.5. 
Clinician Reported Photonumeric Cellulite Severity Scale ........................................63 
9.2. 
Efficacy Assessments .................................................................................................64 
9.2.1. 
Digital Photography ....................................................................................................64 
9.2.2. 
Investigator Assessment of Bruising Severity Scale ..................................................64 
9.2.3. 
Investigator-Global Aesthetic Improvement Scale .....................................................65 
9.3. 
Safety Assessments .....................................................................................................65 
9.3.1. 
Vital Signs ..................................................................................................................65 
9.3.2. 
Pregnancy Testing ......................................................................................................66 
9.3.3. 
Clinical Laboratory Determinations ...........................................................................66 
9.4. 
Adverse Events and Serious Adverse Events .............................................................66 
9.4.1. 
Time Period and Frequency for Collecting Adverse Event and Serious 
Adverse Event Information .........................................................................................67 
9.4.2. 
Method of Detecting Adverse Events and Serious Adverse Events ...........................67 
9.4.3. 
Follow-up of Adverse Events and Serious Adverse Events .......................................67 
9.4.4. 
Regulatory Reporting Requirements for Serious Adverse Events..............................67 
9.4.5. 
Pregnancy ...................................................................................................................68 
9.5. 
Treatment Overdose ....................................................................................................68 
10. 
STATISTICAL CONSIDERATIONS AND METHODS .........................................69 
10.1. 
Sample Size Determination ........................................................................................69 

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10.2. 
Populations for Analysis .............................................................................................69 
10.3. 
Statistical Hypotheses and Analyses ..........................................................................69 
10.3.1. 
Efficacy Analysis ........................................................................................................69 
10.3.2. 
Safety Analyses ..........................................................................................................70 
10.3.2.1. 
Adverse Events ...........................................................................................................70 
10.3.2.2. 
Clinical Laboratory Tests and Vital Signs ..................................................................70 
11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................71 
11.1. 
Appendix 1: Regulatory, Ethical and Study Oversight Considerations......................71 
11.1.1. 
Regulatory and Ethical Considerations ......................................................................71 
11.1.2. 
Financial Disclosure ...................................................................................................71 
11.1.3. 
Informed Consent Process ..........................................................................................72 
11.1.4. 
Data Protection ...........................................................................................................72 
11.1.5. 
Dissemination of Clinical Study Data ........................................................................73 
11.1.6. 
Data Quality Assurance ..............................................................................................73 
11.1.7. 
Source Documents ......................................................................................................73 
11.1.8. 
Study and Site Closure ................................................................................................74 
11.1.9. 
Publication Policy .......................................................................................................74 
11.2. 
Appendix 2: Clinical Laboratory Tests .......................................................................75 
11.3. 
Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up and Reporting .........................................................................76 
11.3.1. 
Definitions ..................................................................................................................76 
11.3.2. 
Relationship to Study Intervention .............................................................................77 
11.3.3. 
Intensity Assessment ..................................................................................................77 
11.3.4. 
Reporting Adverse Events and Serious Adverse Events ............................................77 
11.3.4.1. 
Reporting Adverse Events ..........................................................................................77 
11.3.4.2. 
Reporting Serious Adverse Events .............................................................................78 
11.3.4.3. 
Follow-up Procedures for Serious Adverse Events ....................................................78 
11.4. 
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information .................................................................................................................79 
11.5. 
Appendix 5: Amendment 01 .......................................................................................80 
11.6. 
Abbreviations ..............................................................................................................85 
12. 
INVESTIGATOR’S STATEMENT ...........................................................................86 

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13. 
REFERENCES ...........................................................................................................87 
 
LIST OF TABLES 
Table 1: 
Study Intervention Cohorts .........................................................................................39 
Table 2: 
Study Intervention (CCH-aaes) by Buttock ................................................................53 
Table 3: 
Study Intervention (Tranexamic Acid) in Cohort 7 ....................................................54 
Table 4: 
Hexsel Cellulite Severity Scale ..................................................................................63 
Table 5: 
Investigator-Global Aesthetic Improvement Scale (I-GAIS) .....................................65 
 
LIST OF FIGURES 
Figure 1: 
Primary Endpoints for Cohorts 7a and 7b ..................................................................45 
Figure 2: 
Secondary Endpoints (Within Cohort Comparison) for Cohorts 7a and 7b ...............45 
Figure 3: 
Exploratory (Cross-Cohort Comparisons) for Cohorts 7a and 7b ..............................46 
 
 

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1. 
SUMMARY OF CHANGES 
Amendment 02 
The primary reason for Amendment 02 was to add Cohort 7 as a new investigation. The major 
changes to the protocol are outlined below. Revisions in style, minor corrections (such as 
spelling errors, etc), and other minor changes that do not impact content may also have been 
made. 
Section 
Reason for Change/ 
Original Text 
Revision 
Global 
Identified additional methods for 
preventing bruising  
Change the total number of 
cohorts in the study from 6 to 7. 
Section 2.1, Synopsis, Overall 
Design 
Section 5.1, Overall Design 
Section 10.1, Sample Size 
Determination 
Added an additional cohort 
(Cohort 7). 
Change sample size from 180 to 
210 participants with 168 
completers. 
Section 2.1, Synopsis, Overall 
Design 
Section 2.2 and Section 2.3, 
Study Schemas for Cohorts 1-5 
and Cohort 6 
Section 2.6 and Section 2.7, 
Schedules of Assessment for 
Cohorts 1-5 and Cohort 6 
Section 5.1, Overall Design 
Added an additional cohort 
(Cohort 7). 
Modify duration of the 
Treatment Period from 56 to 90 
days for Cohorts 1-6 and 
Cohorts 7a and 7b. 
Section 2.1, Synopsis, Overall 
Design 
Section 5.1, Overall Design 
Added an additional cohort 
(Cohort 7). 
Included method of 
administration of QWO and 
tranexamic acid in Cohort 7. 
Section 2.4 and Section 2.5, 
Study Schemas for Cohort 7a 
and Cohort 7b 
Added an additional cohort 
(Cohort 7). 
Added study schematic diagrams 
for Cohorts 7a and 7b. 
Section 2.8 and Section 2.9, 
Schedules of Assessments for 
Cohort 7a and Cohort 7b 
Added an additional cohort 
(Cohort 7). 
Added schedule of assessments 
to account for the addition of 
Cohort 7a and 7b. 
Section 3.3.6, Tranexamic Acid 
Added an additional cohort 
(Cohort 7). 
Added the risks and benefits of 
tranexamic acid to account for 
the addition of Cohort 7. 

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Section 
Reason for Change/ 
Original Text 
Revision 
Section 4.1, Objective and 
Endpoints and Study Synopsis 
Added an additional cohort 
(Cohort 7). 
Added a new primary endpoint 
for Cohorts 7a and 7b and 
specified that the previous 
endpoint was for Cohorts 1-6. 
Added additional secondary and 
exploratory endpoints for 
Cohort 7. 
Modified secondary endpoint for 
the I-GAIS assessments to add 
the visit at Day 64 in Cohort 7. 
Section 5.2, Scientific Rationale 
for Study Design 
Added an additional cohort 
(Cohort 7). 
Added rationale for additional 
visits and asynchronous 
administration of QWO (CCH-
aaes) and tranexamic acid in 
Cohort 7.  
Section 5.3, Justification of 
Endpoints 
Added an additional cohort 
(Cohort 7). 
Added rationale for modification 
of primary endpoint in Cohort 7, 
during which the first treatment 
for the investigational cohort 
will be staggered. 
Section 5.4, Justification for 
Dose 
Added an additional cohort 
(Cohort 7). 
Added justification for the dose 
of tranexamic acid. 
Section 6.1, Participant Inclusion 
Criteria 
Account for risk of thrombosis 
with tranexamic acid 
Modified inclusion criterion #6 
to exclude oral contraceptive use 
as an acceptable method of 
contraception, specific to 
Cohort 7. 
Section 6.2, Participant 
Exclusion Criteria 
Account for the exclusion 
criteria to tranexamic acid 
For all cohorts, added additional 
exclusion criteria to exclude 
participants taking tranexamic 
acid before treatment. 
Added additional exclusion 
criteria for Cohort 7. 
Section 6.3, Lifestyle 
Considerations 
Account for risk of thrombosis 
with tranexamic acid 
For Cohort 7, added that 
participants should not smoke 
during the study. 
Section 7.1, Selection and 
Marking of Dimples 
Added an additional cohort 
(Cohort 7). 
Added the timepoints for 
selection and marking of 
dimples for Cohort 7. 
Section 7.2.1, Table 2, Study 
Intervention (QWO -CCH-aaes) 
by Buttock 
Added an additional cohort 
(Cohort 7). 
Added QWO (CCH-aaes) for 
Cohort 7 and clarified in title for 
QWO (CCH-aaes). 

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Section 
Reason for Change/ 
Original Text 
Revision 
Section 7.2.1, Table 3, Study 
Intervention (Tranexamic Acid) 
in Cohort 7 
Added an additional cohort 
(Cohort 7). 
Added tranexamic acid for 
Cohort 7. 
Section 7.2.9, Cohort 6, Control 
Side Only, QWO (CCH-aaes) – 
Half of the Labeled Dose 
(0.42 mg/control side) Using the 
Labeled Concentration 
(0.23 mg/mL) at Approximately 
42 Days between Visits 
 
Added details of treatment 
administration for the control 
side. Previously only the 
investigational side was 
delineated. 
Section 7.2.10, Labeled dose and 
concentration of QWO (CCH-
aaes) and Tranexamic Acid 
Added an additional cohort 
(Cohort 7). 
Added details of study 
intervention for Cohort 7. 
Section 7.2.12, Preparation/ 
Handling/Storage/Accountability 
Added an additional cohort 
(Cohort 7). 
Added details of study 
intervention for Cohort 7. 
Section 7.3, Measures to 
Minimize Bias, Global 
Added an additional cohort 
(Cohort 7). 
Updated the number of cohorts 
for randomization. 
Section 7.4, Study Intervention 
Compliance 
Added an additional cohort 
(Cohort 7). 
Added text to account for 
compliance checks with 
tranexamic acid use. 
Section 7.5.1, Prohibited 
Medications/Procedures 
Added an additional cohort 
(Cohort 7). 
For all participants, added 
prohibited medication of 
tranexamic acid 30 days before 
treatment. 
Added prohibited medications 
(eg, combination hormonal 
contraceptives) for Cohort 7. 
Section 9.2.1, Digital 
Photography 
Added an additional cohort 
(Cohort 7). 
Add additional timepoint of Day 
64 for Cohort 7. 
Section 9.3.1, Vital Signs  
Added an additional cohort 
(Cohort 7). 
Add additional timepoint of Day 
64 for Cohort 7. 
Section 11.1.1, Regulatory 
Considerations 
Added an additional cohort 
(Cohort 7). 
Added reference to providing the 
Tranexamic Acid Prescribing 
Information to the local IRBs. 
Section 11.5, Appendix 5: 
Amendment 01 
Formatting change 
Moved summary of changes for 
Amendment 01 to the end of the 
protocol. 
 

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2. 
PROTOCOL SUMMARY 
2.1. 
Synopsis 
Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Marketed Product: QWO (CCH-aaes) 
Name of Active Ingredient: Collagenase clostridium histolyticum (CCH) 
Title of Study: APHRODITE-1: A PHase 2, Open Label, Self-ContROlled Study of DIfferent 
Interventions to Reduce Bruising Following CCH-Aaes TrEatment for Cellulite of the Buttocks in Adult 
Females 
Lead Principal Investigator: Not applicable 
Phase of development: 2 
Objectives and Endpoints:  
Objectives 
Endpoints 
Primary 
• To assess the effects of interventions on bruising 
of the buttocks of participants with cellulite after 
the first treatment with QWO (CCH-aaes).  
• Cohorts 1 to 6: The proportion of participants 
whose left buttock (investigational side) 
demonstrates at least 1-level lower score versus the 
right buttock (control side) on the Investigator 
Assessment of Bruising Severity Scale (IABSS), at 
Visit 3, three to 5 days after initial QWO (CCH-
aaes) injection. The IABSS is a 5-point scale 
ranging from 0-4, with 0 indicating no bruising or 
almost none, and 4 indicating very severe bruising. 
• Cohort 7a: The proportion of participants whose 
left buttock (investigational side), at Visit 3, 
demonstrates at least 1-level lower score versus the 
right buttock (control side), at Visit 8 on the 
Investigator Assessment of Bruising Severity Scale 
(IABSS). These visits are three to 5 days after 
initial QWO (CCH-aaes) injection for each 
respective buttock. 
•  Cohort 7b: The proportion of participants whose 
left buttock (investigational side), at Visit 8, 
demonstrates at least 1-level lower score versus the 
right buttock (control side), at Visit 3, on the 
Investigator Assessment of Bruising Severity Scale 
(IABSS). These visits are three to 5 days after 
initial QWO (CCH-aaes) injection for each 
respective buttock.  
Secondary 
• To assess the effects of interventions on bruising 
of the buttocks of participants with cellulite after 
each treatment with QWO (CCH-aaes). 
• The proportion of participants whose left buttock 
(investigational side) demonstrates at least 1 level 
lower score versus the right buttock (control side) 
on the IABSS, by visit. The IABSS is a 5-point 
scale ranging from 0-4, with 0 indicating no 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Marketed Product: QWO (CCH-aaes) 
Name of Active Ingredient: Collagenase clostridium histolyticum (CCH) 
bruising or almost none, and 4 indicating very 
severe bruising. 
• Cohorts 7a and 7b: The proportion of participants 
within each cohort (i.e. 7a and 7b) whose left 
buttock (investigational side) demonstrates at least 
1-level lower score versus the right buttock 
(control side), on the IABSS, by corresponding 
treatment visit by buttock (first dose of QWO 
[CCH-aaes] on the investigational buttock with 
tranexamic acid vs the first dose of QWO [CCH-
aaes] without tranexamic acid on the control side; 
second dose of QWO [CCH-aaes] on the 
investigational buttock vs second dose of QWO 
[CCH-aaes] on the control side; third dose of 
QWO [CCH-aaes] on the investigational side vs 
third dose of QWO [CCH-aaes] on the control 
side); and at each follow up visit thereafter.  
• To assess the level of aesthetic improvement of 
cellulite after treatment with QWO (CCH-aaes). 
• The proportion of participants with an improved 
(+1 or better) score on the Investigator-Global 
Aesthetic Improvement Scale (I-GAIS) by 
treatment area at Days 22, 43, 64, 90, 135 and 180 
Visits. The I-GAIS is a 7-point scale ranging from 
+3 (very much improved) to -3 (very much worse). 
• To assess the safety of QWO (CCH-aaes) for each 
study intervention in participants with cellulite. 
• Proportion of participants reporting each 
treatment-emergent adverse events (TEAEs) 
throughout the study. 
• To assess the safety of QWO (CCH-aaes) in 
participants for each study intervention in 
participants with cellulite.  
• Proportion of participants reporting TEAEs of 
injection site reactions in the left buttock 
(investigational side) vs the right buttock (control 
side). 
Exploratory 
• 
 
 
  
• 
 
 
 
 
 
 
 
• 
 
 
 
 
 
 
 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Marketed Product: QWO (CCH-aaes) 
Name of Active Ingredient: Collagenase clostridium histolyticum (CCH) 
Overall Design: This is a Phase 2 open-label, self-controlled study to assess different interventions 
designed to reduce bruising following QWO (CCH-aaes) treatment of moderate to severe cellulite of the 
buttocks in adult females. The study is expected to enroll approximately 210 participants, with up to 30 
participants allocated to each of 7 cohorts.  
The study will comprise a Screening Period, a Treatment Period, and a Follow-up Period. After the 
Screening Period on Day 1, participants who meet study criteria will be assigned to 1 of 7 study 
intervention cohorts using an interactive response technology (IRT) system (table below). Participants 
will receive QWO (CCH-aaes) in different doses, concentrations, diluent additives, depths of injection, 
and methods of injection in a split buttock arrangement, with the right buttock serving as the control, and 
the left buttock (investigational side) receiving a study intervention.  
Study Intervention Cohorts 
Cohort 
N 
Study Interventions Tested 
Left Buttock – 
Investigational Side 
Right Buttock – Control Side 
Cohort 1 
30 
Labeled dose (0.84 mg/control 
side) of QWO (CCH-aaes) vs 
half the labeled dose 
(0.42 mg/investigational side) 
Labeled injection technique 
(3 aliquots) using half the labeled 
dose (0.42 mg/investigational 
side) but maintaining the labeled 
concentration (0.23 mg/mL). 
Labeled injection technique 
(3 aliquots) using the labeled 
dose (0.84 mg/control side) and 
concentration (0.23 mg/mL). 
Cohort 2 
30 
Labeled dose (0.84 mg/buttock) 
and concentration of QWO 
(CCH-aaes) vs an ~5-fold 
dilution of the labeled 
concentration 
Labeled injection technique 
(3 aliquots) using the labeled 
dose (0.84 mg/investigational 
side) but using a ~ 5-fold dilution 
(0.05 mg/mL) of the labeled 
concentration (0.23 mg/mL) 
Labeled injection technique 
(3 aliquots) using the labeled 
dose (0.84 mg/control side) and 
concentration (0.23 mg/mL). 
Cohort 3 
30 
Labeled dose (0.84 mg/buttock) 
and concentration of QWO 
(CCH-aaes) at an injection depth 
of ½ inch vs ¼ inch 
Labeled injection technique 
(3 aliquots) using the labeled 
dose (0.84 mg/investigational 
side) and concentration 
(0.23 mg/mL) but with an 
injection depth of ¼ inch. 
Labeled injection technique 
(3 aliquots) using the labeled 
dose (0.84 mg/area) and 
concentration (0.23 mg/mL). 
Labeled injection at labeled 
depth of ½ inch. 
Cohort 4 
30 
Labeled dose (0.84 mg/buttock) 
and concentration of QWO 
(CCH-aaes) vs. an ~2.5-fold 
dilution of the labeled 
concentration AND a single 
aliquot at ¼-inch depth of 
injection (both buttocks) 
Labeled dose (0.84 mg/ 
investigational side) using an 
~2.5-fold dilution (0.09 mg/mL) 
of the labeled concentration but 
administering only a single 
aliquot at ¼-inch depth per 
injection administered as up to 
30 injections. 
Labeled dose (0.84 mg/control 
side) and concentration 
(0.23 mg/mL) but administering 
only a single aliquot at ¼-inch 
depth per injection administered 
as up to 12 injections. 
Cohort 5 
30 
Labeled dose (0.84 mg/control 
side) and concentration of QWO 
(CCH-aaes) vs half the labeled 
dose (0.42 mg/investigational 
side) of QWO (CCH-aaes) with 
lidocaine 2% and epinephrine 
1:200,000 utilized as diluent 
additive. 
Labeled injection technique 
(3 aliquots) using half the labeled 
dose (0.42 mg/investigational 
side) with lidocaine 2% and 
epinephrine 1:200,000 as diluent 
additive. 
Labeled injection technique 
(3 aliquots) using the labeled 
dose (0.84 mg/control side) and 
concentration (0.23 mg/mL). 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Marketed Product: QWO (CCH-aaes) 
Name of Active Ingredient: Collagenase clostridium histolyticum (CCH) 
Cohort 6 
30 
Half of the labeled dose 
(0.42 mg/control side) while 
maintaining the labeled 
concentration (0.23 mg/mL) of 
QWO (CCH-aaes) vs one-quarter 
of the labeled dose 
(0.21 mg/investigational side) 
at -one-half the labeled 
concentration (0.12 mg/mL) with 
both the control and 
investigational sides receiving 
only 2 treatment sessions 
administered 6 weeks apart. 
Labeled injection technique 
(3 aliquots) using one-quarter of 
the labeled dose 
(0.21 mg/investigational side) at 
one-half the labeled 
concentration (0.12 mg/mL). 
Treatment sessions will be 
administered 6 weeks apart. 
Labeled injection technique 
(3 aliquots) using one-half the 
labeled dose (0.42 mg/control 
side) but maintaining the labeled 
concentration (0.23 mg/mL). 
Treatment sessions will be 
administered 6 weeks apart. 
Cohort 7a 
15 
Labeled dose (0.84 mg/side) and 
concentration (0.23 mg/mL) of 
QWO (CCH-aaes) with oral 
tranexamic acid.  
Labeled dose (0.84 mg/side), injection technique, and concentration 
(0.23 mg/mL) of QWO (CCH-aaes) to both the investigational and 
control buttocks. 
Participants will be receiving tranexamic acid 1300 mg orally three 
times a day (TID) for 5 days (on Day -1, prior to the day of the first 
injection on Day 1 and for the 3 days after the first injection of QWO 
(CCH-aaes) to the investigational side on Days 2-4, during the first 
treatment session. 
Cohort 7b 
15 
Labeled dose (0.84 mg/side) and 
concentration (0.23 mg/mL) of 
QWO (CCH-aaes) with oral 
tranexamic acid.  
Labeled dose (0.84 mg/side), injection technique, and concentration 
(0.23 mg/mL) of QWO (CCH-aaes) to both the investigational and 
control buttocks.  
Participants will be receiving tranexamic acid 1300 mg orally TID for 
5 days (prior to the day of the first injection on Day 21, the day of the 
first injection, Day 22, and for the 3 days following the first injection 
on Days 23-25) during the second treatment session. Investigational 
side will not receive QWO (CCH-aaes) during the first treatment 
session. 
All participants will receive QWO (CCH-aaes) throughout the study to both the investigational and the 
control sides. Enrolled participants assigned to Cohorts 1 and 5 will receive a maximum dose of up to 
0.84 mg of QWO (CCH-aaes) on the control side and a maximum dose of up to 0.42 mg of QWO (CCH-
aaes) to the investigational side per treatment session (Days 1, 22, and 43) for a maximum total dose of 
3.78 mg. Participants assigned to Cohorts 2, 3, and 4 will receive a maximum dose of up to 0.84 mg of 
QWO (CCH-aaes) per treatment area (to the control and investigational sides) per treatment session (total 
maximum dose of 1.68 mg per treatment session × 3 treatment sessions [Days 1, 22, and 43] for a 
maximum total dose of 5.04 mg). Participants in Cohort 6 will receive a maximum dose of up to 0.42 mg 
of QWO (CCH-aaes) on the control side and a maximum dose of up to 0.21 mg of QWO (CCH-aaes) to 
the investigational side per treatment session×2 treatment sessions (Days 1 and 43) for a maximum total 
dose of 1.26 mg. Participants in Cohorts 1-6 have their final, scheduled treatment visit on Day 43. 
All participants in Cohort 7 will receive a maximum dose of up to 0.84 mg of QWO (CCH-aaes) on the 
control side and a maximum dose of up to 0.84 mg of QWO (CCH-aaes) to the investigational side per 
treatment session×3 treatment sessions for a maximum total dose of 5.04 mg. Participants in Cohort 7a 
will have the investigational side treated on Days 1, 22, and 43 with the control side treated on Days 22, 
43 and 64. Treatment will be staggered for participants in Cohort 7b vs Cohort 7a; the investigational 
side treated on Days 22, 43, and 64 and the control side treated on Days 1, 22, and 43.  Tranexamic acid 
will be provided by the sponsor and self-administered by all participants enrolled in Cohort 7. 
Participants in Cohort 7a will take tranexamic acid 1300 mg orally TID for 5 days (prior to the day of the 

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Name of Sponsor/Company: Endo Pharmaceuticals Inc. 
Name of Marketed Product: QWO (CCH-aaes) 
Name of Active Ingredient: Collagenase clostridium histolyticum (CCH) 
first injection of QWO (CCH-aaes) of the investigational buttock (Day -1) , the day of the first injection 
(Day 1) and for the 3 days following the first injection (Days 2 to 4). Participants in Cohort 7b will take 
tranexamic acid orally TID for 5 days (prior to the day of the second injection on Day 21, the day of the 
second injection (Day 22) and for the 3 days following the second injection (Day 23 to Day 25). All 
participants in Cohort 7, will have an additional treatment visit on Day 64. 
Bruising will be observed throughout the study. In an effort to standardize the risk and scope of bruising, 
the investigational and control sides in Cohorts 1 and 5 should be treated with the same concentration and 
number of injections and same number of aliquots per injection, but at different doses per injection or 
addition of diluent additive. In Cohort 2, the investigational and control sides will be treated with the 
same dose and number of injections, but the concentration will vary. In Cohort 3, the investigational and 
control sides will be treated with the same dose, aliquots per injection, and number of injections but at 
different injection depths. In Cohort 4, the dose will remain consistent between buttocks, but the number 
of injections and concentration will vary between the investigational and control sides. In Cohort 6, the 
investigational and control sides will be treated with the same number of injections, the same number of 
aliquots per injection, and an extended treatment interval, but at different doses and concentrations. In 
Cohort 7, the investigational and control sides should be treated with the labeled dose, injection 
technique and concentration of QWO (CCH-aaes) during each treatment visit, but oral tranexamic acid 
will be given before and after the first treatment with QWO (CCH-aaes) for the investigational buttock.  
Participants will return to the site for 4 follow-up visits (1 to 2 days, 3 to 5 days, 6 to 9 days, and 10 to 
14 days) after each treatment of QWO (CCH-aaes), for additional evaluations and digital photography to 
monitor the severity of bruising. Digital photographs will be obtained using a standardized method at 
each visit throughout the study. The effect of the different QWO (CCH-aaes) doses, strengths 
(concentrations), diluent additives, depths of injection, and methods of injection on the severity of 
bruising will be assessed by the Investigator using the IABSS. The investigators will be evaluating the 
left (investigational) and right (control) buttocks separately with the IABSS. To assess the effect of QWO 
(CCH-aaes) on the severity of cellulite, the investigator will complete the I-GAIS. Each buttock will be 
evaluated separately.  
After completing the Treatment Period, participants will return for 3 follow-up visits at Days 90, 135, 
and Day 180 (EOS Visit). At the EOS visit, the investigator will complete the I-GAIS, and safety 
assessments will be evaluated. The total duration of study participation, including the Screening 
(28 days), Treatment (90 days), and Follow-up Periods (90 days), is approximately 208 days. 
Disclosure Statement: This is an interventional open-label, Phase 2 study to evaluate the effect of 
different doses, strengths (concentrations), diluent additives, depths of injection, and methods of injection 
on the severity of bruising potentially induced by QWO (CCH-aaes).  
Number of Participants (planned): Adult females will be screened to enroll approximately 210 
participants into 7 treatment cohorts of up to 30 participants each, such that up to 168 participants 
complete the study. 
Treatment Groups and Duration: It is intended to enroll 7 treatment cohorts of up to 30 participants 
each. See the Study Intervention Cohorts table above for further details regarding the treatment cohorts.  
Duration: The total duration of study participation, including the Screening (28 days), Treatment 
(90 days), and Follow-up Periods (90 days), is approximately 208 days. 
Data Monitoring Committee: No data monitoring committee will be used for this study. 
 

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2.2. 
Study Schema for Cohorts 1 to 5 
 
 
EOS = End of Study; FU = follow-up; Tx = Treatment; V = visit 

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2.3. 
Study Schema for Cohort 6 
 
EOS = End of Study; FU = follow-up; Tx = Treatment; V = visit 

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2.4. 
Study Schema for Cohort 7a 
 
 
 

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2.5. 
Study Schema for Cohort 7b 
 
 

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2.6. 
Schedule of Assessments for Cohorts 1 to 5 
Activities 
Screening 
28 days 
Treatment Period 
90 days 
Follow-Up Period 
90 days 
Visit Number 
Screening 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
Visit 
Screening 
Tx Visit 1 
Tx V1 FU1 
Tx V1 FU2 
Tx V1 FU3 
Tx V1 FU4 
Tx Visit 2 
Tx V2 FU1 
Tx V2 FU2 
Tx V2 FU3 
Tx V2 FU4 
Tx Visit 3 
Tx V3 FU1 
Tx V3 FU2 
Tx V3 FU3 
Tx V3 FU4 
90 Day 
 Follow-Up 
Visit 
135 Day  
Follow-Up 
Visit 
EOS / ET 
 Visito 
Visit Windows (Days) 
(Day -28 to Day -1) 
Day 1 
1 to 2 Days After TV1 
3 to 5 Days After TV1 
6 to 9 Days After TV1 
10 to 14 Days After TV1 
Day 22 
(±3 Days) 
1 to 2 Days After TV2 
3 to 5 Days After TV2 
6 to 9 Days After TV2 
10 to 14 Days After TV2 
Day 43 
(±3 Days) 
1 to 2 Days After TV3 
3 to 5 Days After TV3 
6 to 9 Days After TV3 
10 to 14 Days After TV3 
Day 90 
(±7 Days) 
Day 135 
(±7 Days) 
Day 180 
 (±7 Days) 
Informed consenta 
X 
Inclusion/Exclusion criteria 
review 
X 
Xb  
Clinician Reported 
Photonumeric Cellulite 
Severity Scale (CR-PCSS)c,d 
X 
Xb 
Hexsel Cellulite Severity 
Scale (CSS)c,d 
X 
Xb 
Cohort assignmente  
  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical and surgical historyf  
X 
Cellulite history 
X 
Physical examination 
(including height) 
X 
Weight 
X 
X 
X 
Fitzpatrick Skin Type d 
X 
Vital signs 
X 
Xg  
Xg 
Xg 
X 
Clinical laboratory tests 
(chemistry, hematology, 
urinalysis) 
X 
X 
Serum pregnancy test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Urine pregnancy test 
 
Xh 
 
 
 
 
Xh 
 
 
 
 
Xh 
 
 
 
 
 
 
 

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Activities 
Screening 
28 days 
Treatment Period 
90 days 
Follow-Up Period 
90 days 
Visit Number 
Screening 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
Visit 
Screening 
Tx Visit 1 
Tx V1 FU1 
Tx V1 FU2 
Tx V1 FU3 
Tx V1 FU4 
Tx Visit 2 
Tx V2 FU1 
Tx V2 FU2 
Tx V2 FU3 
Tx V2 FU4 
Tx Visit 3 
Tx V3 FU1 
Tx V3 FU2 
Tx V3 FU3 
Tx V3 FU4 
90 Day 
 Follow-Up 
Visit 
135 Day  
Follow-Up 
Visit 
EOS / ET 
 Visito 
Visit Windows (Days) 
(Day -28 to Day -1) 
Day 1 
1 to 2 Days After TV1 
3 to 5 Days After TV1 
6 to 9 Days After TV1 
10 to 14 Days After TV1 
Day 22 
(±3 Days) 
1 to 2 Days After TV2 
3 to 5 Days After TV2 
6 to 9 Days After TV2 
10 to 14 Days After TV2 
Day 43 
(±3 Days) 
1 to 2 Days After TV3 
3 to 5 Days After TV3 
6 to 9 Days After TV3 
10 to 14 Days After TV3 
Day 90 
(±7 Days) 
Day 135 
(±7 Days) 
Day 180 
 (±7 Days) 
Selection and marking of 
dimples to be treated within 
both buttocks 
 
Xh 
 
 
 
 
Xh 
 
 
 
 
Xh 
 
 
 
 
 
 
 
Digital photographyi  
X 
Xj  
X 
X 
X 
X 
Xj  
X 
X 
X 
X 
Xj  
X 
X 
X 
X 
X 
X 
X 
QWO (CCH-aaes) 
administrationd 
(Investigational and Control 
Buttocks) 
 
X 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
Investigator Assessment of 
Bruising Severity Scale 
(IABSS) d,k 
 
Xh 
X 
X 
X 
X 
Xh 
X 
X 
X 
X 
Xh 
X 
X 
X 
X 
 
 
 
Investigator-Global 
Aesthetic Improvement 
Scale (I-GAIS) d,k,l  
 
 
 
 
 
 
Xh 
 
 
 
 
Xh 
 
 
 
 
X 
X 
X 
Prior medicationsm  
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant 
medications/procedures 
Collect throughout the study 
Adverse eventsn  
Collect throughout the study 
a Performed prior to any study-required assessments. 
b Reassessed and verified prior to dosing.  
c CR-PCSS rating must be a ‘3’ (moderate) or ‘4’ (severe) on each buttock and the Hexsel CSS total score must be ≤ 12. 
d To be performed by a qualified designated physician. 
e Participants will be assigned to 1 of 7 cohorts using an interactive response technology (IRT) system.  

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f Medical and surgical history will include a review of all medical history and surgical procedures completed in the prior 10 years and any surgery completed at any time in the 
treatment area. Tobacco and ethanol (EtOH) use will also be collected. 
g Vital signs (temperature, pulse, systolic blood pressure, and diastolic blood pressures) will be collected up to 2 hours prior to, and at 15 and 30 minutes after, QWO (CCH-aaes) 
administration on the days of treatment. Pulse and blood pressure will be collected after the participant has been sitting for 5 minutes. 
h Prior to treatment with QWO (CCH-aaes). 
i No manipulation of the treatment area should be done prior to any “before” images. 
j On the days of treatment, the buttocks will be photographed before and after injection site and dimple marking.  
k Based on live assessments while the participant is in front of the investigator. Assessments will be performed for each buttock separately.  
l 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 during the live assessment. 
m Prior medications (other than QWO [CCH-aaes]) include medications taken 90 days before Screening. All prior QWO (CCH-aaes) use should be captured. 
n Serious adverse events (SAEs) and adverse events (AEs) will be collected by the investigator from the time of signing the informed consent through the Day 180 EOS/ET Visit. 
All ongoing AEs must be followed until they have resolved or for 28 days after the participant’s last treatment visit, whichever comes first. For participants who withdraw from 
the study early, SAEs and AEs will be collected for 28 days after the last dose of QWO (CCH-aaes).  
o Participants are encouraged to remain in the study for follow-up until the Day 180 Visit. Participants who discontinue from the study or study intervention and do not agree to 
remain in the study for follow-up until Day 180, will be asked to complete an early termination (ET) visit and a 28-day post-treatment Safety Follow-up Visit (or phone call if a 
visit is not possible) if applicable. The status of any ongoing AEs/SAEs or the occurrence of any new AEs/SAEs will be assessed. 
EOS = end of study; FU = follow-up; Tx = Treatment; V = visit 
 

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2.7. 
Schedule of Assessments for Cohort 6 
Activities 
Screening 
28 days 
Treatment Period  
90 days 
Follow-Up Period 
90 days 
Visit Number 
Screening 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
Visit 
Screening 
Tx Visit 1 
Tx V1 FU1 
Tx V1 FU2 
Tx V1 FU3 
Tx V1 FU4 
Tx V1 FU5 
Tx Visit 2 
Tx V2 FU1 
Tx V2 FU2 
Tx V2 FU3 
Tx V2 FU4 
90 Day 
Follow-Up 
Visit 
135 Day 
Follow-Up 
Visit 
EOS / ET 
Visito 
Visit Windows (Days) 
(Day -28 to Day -1) 
Day 1 
1 to 2 Days After TV1 
3 to 5 Days After TV1 
6 to 9 Days After TV1 
10 to 14 Days After TV1 
18 to 24 Days After TV1 
 (Day 22 ± 3 Days) 
Day 43 (±3 Days) 
1 to 2 Days After TV2 
3 to 5 Days After TV2 
6 to 9 Days After TV2 
10 to 14 Days After TV2 
Day 90 (±7 Days) 
Day 135 (±7 Days) 
Day 180 (±7 Days) 
Informed consenta 
X 
Inclusion/Exclusion criteria 
review 
X 
Xb 
Clinician Reported 
Photonumeric Cellulite 
Severity Scale (CR-PCSS)c,d 
X 
Xb 
Hexsel Cellulite Severity 
Scale (CSS)c,d 
X 
Xb 
Cohort assignmente 
X 
Medical and surgical historyf 
X 
Cellulite history 
X 
Physical examination 
(including height) 
X 
Weight 
X 
X 
X 
Fitzpatrick Skin Type d 
X 
Vital signs 
X 
Xg 
 
Xg 
X 
Clinical laboratory tests 
(chemistry, hematology, 
urinalysis) 
X 
X 

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Activities 
Screening 
28 days 
Treatment Period  
90 days 
Follow-Up Period 
90 days 
Visit Number 
Screening 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
Visit 
Screening 
Tx Visit 1 
Tx V1 FU1 
Tx V1 FU2 
Tx V1 FU3 
Tx V1 FU4 
Tx V1 FU5 
Tx Visit 2 
Tx V2 FU1 
Tx V2 FU2 
Tx V2 FU3 
Tx V2 FU4 
90 Day 
Follow-Up 
Visit 
135 Day 
Follow-Up 
Visit 
EOS / ET 
Visito 
Visit Windows (Days) 
(Day -28 to Day -1) 
Day 1 
1 to 2 Days After TV1 
3 to 5 Days After TV1 
6 to 9 Days After TV1 
10 to 14 Days After TV1 
18 to 24 Days After TV1 
 (Day 22 ± 3 Days) 
Day 43 (±3 Days) 
1 to 2 Days After TV2 
3 to 5 Days After TV2 
6 to 9 Days After TV2 
10 to 14 Days After TV2 
Day 90 (±7 Days) 
Day 135 (±7 Days) 
Day 180 (±7 Days) 
Serum pregnancy test 
X 
X 
Urine pregnancy test 
Xh 
 
Xh 
Selection and marking of 
dimples to be treated within 
both buttocks 
Xh 
 
Xh 
Digital photographyi 
X 
Xj 
X 
X 
X 
X 
X 
Xj 
X 
X 
X 
X 
X 
X 
X 
QWO (CCH-aaes) 
administration d 
(Investigational and Control 
Buttocks) 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Investigator Assessment of 
Bruising Severity Scale 
(IABSS)d,k 
Xh 
X 
X 
X 
X 
X 
Xh 
X 
X 
X 
X 
 
 
 
Investigator-Global Aesthetic 
Improvement Scale 
(I-GAIS)d,k,l 
 
 
Xh 
X 
X 
X 
Prior Medicationsm 
X 
X 
 
 
Concomitant 
medications/procedures 
Collect throughout the study 
Adverse Eventsn 
Collect throughout the study 
a Performed prior to any study-required assessments. 
b Reassessed and verified prior to dosing. 

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c CR-PCSS rating must be a ‘3’ (moderate) or ‘4’ (severe) on each buttock and the Hexsel CSS total score must be ≤ 12. 
d To be performed by a qualified designated physician. 
e Participants will be assigned to 1 of 7 cohorts using an interactive response technology (IRT) system. 
f Medical and surgical history will include a review of all medical history and surgical procedures completed in the prior 10 years and any surgery completed at any time in 
the treatment area. Tobacco and ethanol (EtOH) use will also be collected. 
g Vital signs (temperature, pulse, systolic blood pressure, and diastolic blood pressures) will be collected up to 2 hours prior to, and at 15 and 30 minutes after, QWO (CCH-aaes) 
administration on Treatment Visit Days. Pulse and blood pressure will be collected after the participant has been sitting for 5 minutes. 
h Prior to treatment with QWO (CCH-aaes). 
i No manipulation of the treatment area should be done prior to any “before” images. 
j On Treatment Visit Days, the buttocks will be photographed before and after injection site and dimple marking. 
k Based on live assessments while the participant is in front of the investigator. Assessments will be performed for each buttock separately. 
l 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 during the live assessment. 
m Prior medications (other than QWO [CCH-aaes]) include medications taken 90 days before Screening. All prior QWO (CCH-aaes) use should be captured. 
n Serious adverse events (SAEs) and adverse events (AEs) will be collected by the investigator from the time of signing the informed consent through the 
Day 180 EOS/ET Visit. All ongoing AEs must be followed until they have resolved or for 28 days after the participant’s last treatment visit, whichever comes first. For 
participants who withdraw from the study early, SAEs and AEs will be collected for 28 days after the last dose of QWO (CCH-aaes). 
o Participants are encouraged to remain in the study for follow-up until the Day 180 Visit. Participants who discontinue from the study or study intervention and do not 
agree to remain in the study for follow-up until Day 180, will be asked to complete an early termination (ET) visit and a 28-day post-treatment Safety Follow-up Visit (or 
phone call if a visit is not possible) if applicable. The status of any ongoing AEs/SAEs or the occurrence of any new AEs/SAEs will be assessed. 
EOS = end of study; FU = follow-up; Tx = Treatment; V = Visit 
 

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2.8. 
Schedule of Assessments for Cohort 7a 
Activities 
Screening 
28 days 
Treatment Period 
90 days 
Follow-Up Period 
90 days 
Visit Number 
Screening 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
Visit 
Screening 
Tx Visit 1 
Tx V1 FU1 
Tx V1 FU2 
Tx V1 FU3 
Tx V1 FU4 
Tx Visit 2 
Tx V2 FU1 
Tx V2 FU2 
Tx V2 FU3 
Tx V2 FU4 
Tx Visit 3 
Tx V3 FU1 
Tx V3 FU2 
Tx V3 FU3 
Tx V3 FU4 
Tx Visit 4 
Tx V4 FU1 
Tx V4 FU2 
Tx V4 FU3 
Tx V4 FU4 
90 Day 
Follow-up 
Visit 
135 Day 
Follow-up 
Visit 
EOS / ET 
Visitp 
Visit Windows (Days) 
(Day -28 to Day -1) 
Day 1 
1 to 2 Days After TV1 
3 to 5 Days After TV1 
6 to 9 Days After TV1 
10 to 14 Days After TV1 
Day 22 (±3 Days) 
1 to 2 Days After TV2 
3 to 5 Days After TV2 
6 to 9 Days After TV2 
10 to 14 Days After TV2 
Day 43 (±3 Days) 
1 to 2 Days After TV3 
3 to 5 Days After TV3 
6 to 9 Days After TV3 
10 to 14 Days After TV3 
Day 64 (±3 Days) 
1 to 2 Days After TV4 
3 to 5 Days After TV4 
6 to 9 Days After TV4 
10 to 14 Days After TV4 
Day 90 (±7 Days) 
Day 135 (±7 Days) 
Day 180 (±7 Days) 
Informed consenta 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Inclusion/Exclusion 
criteria review 
X 
Xb 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Clinician Reported 
Photonumeric Cellulite 
Severity Scale 
(CR-PCSS)c,d 
X 
Xb 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Hexsel Cellulite Severity 
Scale (CSS)c,d 
X 
Xb 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Cohort assignmente 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Medical and surgical 
historyf 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Cellulite history 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Physical examination 
(including height) 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Weight 
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
Fitzpatrick Skin Type d 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Vital signs 
X 
Xg 
  
  
  
  
Xg 
  
  
  
  
Xg 
  
  
  
  
Xg 
  
  
  
  
  
  
X 
Clinical laboratory tests 
(chemistry, hematology, 
urinalysis) 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
Serum pregnancy test 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
Urine pregnancy test 
  
Xh 
 
  
  
  
Xh 
  
  
  
  
Xh 
  
  
  
  
Xh 
  
  
  
  
  
  
  

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Activities 
Screening 
28 days 
Treatment Period 
90 days 
Follow-Up Period 
90 days 
Visit Number 
Screening 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
Visit 
Screening 
Tx Visit 1 
Tx V1 FU1 
Tx V1 FU2 
Tx V1 FU3 
Tx V1 FU4 
Tx Visit 2 
Tx V2 FU1 
Tx V2 FU2 
Tx V2 FU3 
Tx V2 FU4 
Tx Visit 3 
Tx V3 FU1 
Tx V3 FU2 
Tx V3 FU3 
Tx V3 FU4 
Tx Visit 4 
Tx V4 FU1 
Tx V4 FU2 
Tx V4 FU3 
Tx V4 FU4 
90 Day 
Follow-up 
Visit 
135 Day 
Follow-up 
Visit 
EOS / ET 
Visitp 
Visit Windows (Days) 
(Day -28 to Day -1) 
Day 1 
1 to 2 Days After TV1 
3 to 5 Days After TV1 
6 to 9 Days After TV1 
10 to 14 Days After TV1 
Day 22 (±3 Days) 
1 to 2 Days After TV2 
3 to 5 Days After TV2 
6 to 9 Days After TV2 
10 to 14 Days After TV2 
Day 43 (±3 Days) 
1 to 2 Days After TV3 
3 to 5 Days After TV3 
6 to 9 Days After TV3 
10 to 14 Days After TV3 
Day 64 (±3 Days) 
1 to 2 Days After TV4 
3 to 5 Days After TV4 
6 to 9 Days After TV4 
10 to 14 Days After TV4 
Day 90 (±7 Days) 
Day 135 (±7 Days) 
Day 180 (±7 Days) 
Selection and marking of 
dimples to be treated 
within both buttocks 
  
Xh 
  
  
  
  
Xh 
  
  
  
  
Xh 
  
  
  
  
Xh 
  
  
  
  
  
  
  
Digital photographyi 
X 
Xj 
X 
X 
X 
X 
Xj 
X 
X 
X 
X 
Xj 
X 
X 
X 
X 
Xj 
X 
X 
X 
X 
X 
X 
X 
QWO (CCH-aaes) 
administrationd 
(Investigational Buttock) 
  
Xk 
  
  
  
  
X 
  
  
  
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
QWO (CCH-aaes) 
administrationd 
(Control Buttock) 
  
  
  
  
  
  
X 
  
  
  
  
X 
  
  
  
  
X 
  
  
  
  
  
  
  
Dispensing of tranexamic 
acid  
 X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tranexamic acid use  
 
 
D-1, D1, D2, 
D3, D4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Compliance check for 
tranexamic acid 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Collection of tranexamic 
acid  
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Investigator Assessment 
of Bruising Severity Scale 
(IABSS) d,l 
  
Xh 
X 
X 
X 
X 
Xh 
X 
X 
X 
X 
Xh 
X 
X 
X 
X 
Xh 
X 
X 
X 
X 
  
  
  
Investigator-Global 
Aesthetic Improvement 
Scale (I-GAIS) 
(Investigational Buttock) 
d,l,m 
  
  
  
  
  
  
Xh 
  
  
  
  
Xh 
  
  
  
  
Xh 
  
  
  
  
X 
X 
X 

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Activities 
Screening 
28 days 
Treatment Period 
90 days 
Follow-Up Period 
90 days 
Visit Number 
Screening 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
Visit 
Screening 
Tx Visit 1 
Tx V1 FU1 
Tx V1 FU2 
Tx V1 FU3 
Tx V1 FU4 
Tx Visit 2 
Tx V2 FU1 
Tx V2 FU2 
Tx V2 FU3 
Tx V2 FU4 
Tx Visit 3 
Tx V3 FU1 
Tx V3 FU2 
Tx V3 FU3 
Tx V3 FU4 
Tx Visit 4 
Tx V4 FU1 
Tx V4 FU2 
Tx V4 FU3 
Tx V4 FU4 
90 Day 
Follow-up 
Visit 
135 Day 
Follow-up 
Visit 
EOS / ET 
Visitp 
Visit Windows (Days) 
(Day -28 to Day -1) 
Day 1 
1 to 2 Days After TV1 
3 to 5 Days After TV1 
6 to 9 Days After TV1 
10 to 14 Days After TV1 
Day 22 (±3 Days) 
1 to 2 Days After TV2 
3 to 5 Days After TV2 
6 to 9 Days After TV2 
10 to 14 Days After TV2 
Day 43 (±3 Days) 
1 to 2 Days After TV3 
3 to 5 Days After TV3 
6 to 9 Days After TV3 
10 to 14 Days After TV3 
Day 64 (±3 Days) 
1 to 2 Days After TV4 
3 to 5 Days After TV4 
6 to 9 Days After TV4 
10 to 14 Days After TV4 
Day 90 (±7 Days) 
Day 135 (±7 Days) 
Day 180 (±7 Days) 
Investigator-Global 
Aesthetic Improvement 
Scale (I-GAIS) 
(Control Buttock) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior medicationsn 
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Concomitant medications/ 
procedures 
Collect throughout the study 
Adverse eventso 
Collect throughout the study 
a Performed prior to any study-required assessments. 
b Reassessed and verified prior to dosing. 
c CR-PCSS rating must be a ‘3’ (moderate) or ‘4’ (severe) on each buttock and the Hexsel CSS total score must be ≤ 12. 
d To be performed by a qualified designated physician. 
e Participants will be assigned to 1 of 7 cohorts using an interactive response technology (IRT) system. 
f Medical and surgical history will include a review of all medical history and surgical procedures completed in the prior 10 years and any surgery completed at any time in the 
treatment area. Tobacco and ethanol (EtOH) use will also be collected. 
g Vital signs (temperature, pulse, systolic blood pressure, and diastolic blood pressures) will be collected up to 2 hours prior to, and at 15 and 30 minutes after, QWO (CCH-aaes) 
administration on the days of treatment. Pulse and blood pressure will be collected after the participant has been sitting for 5 minutes. 
h Prior to treatment with QWO (CCH-aaes). 
i No manipulation of the treatment area should be done prior to any “before” images. 
j On the days of treatment, the buttocks will be photographed before and after injection site and dimple marking. 
k Participants will take tranexamic acid 1300 mg orally TID for 5 days (prior to the day of the first injection of QWO (CCH-aaes) to the investigational buttock (Day -1) , the day of the 
first injection (Day 1) and for the 3 days following the first injection (Days 2 to 4). Tranexamic acid use should be documented on the Tranexamic Acid Administration page of the 
eCRF. 
l Based on live assessments while the participant is in front of the investigator. Assessments will be performed for each buttock separately. 
m 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 during the live assessment. 
n Prior medications (other than QWO [CCH-aaes]) include medications taken 90 days before Screening. All prior QWO (CCH-aaes) use should be captured. 

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o Serious adverse events (SAEs) and adverse events (AEs) will be collected by the investigator from the time of signing the informed consent through the Day 180 EOS/ET Visit. All 
ongoing AEs must be followed until they have resolved or for 28 days after the participant’s last treatment visit, whichever comes first. For participants who withdraw from the study 
early, SAEs and AEs will be collected for 28 days after the last dose of QWO (CCH-aaes). 
p Participants are encouraged to remain in the study for follow-up until the Day 180 Visit. Participants who discontinue from the study or study intervention and do not agree to 
remain in the study for follow-up until Day 180, will be asked to complete an early termination (ET) visit and a 28-day post-treatment Safety Follow-up Visit (or phone call if a 
visit is not possible) if applicable. The status of any ongoing AEs/SAEs or the occurrence of any new AEs/SAEs will be assessed. 
EOS = end of study; FU = follow-up; TID = three times daily; Tx = Treatment; V = visit 
 

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2.9. 
Schedule of Assessments for Cohort 7b 
Activities 
Screening 
28 days 
Treatment Period 
90 days 
Follow-Up Period 
90 days 
Visit Number 
Screening 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
Visit 
Screening 
Tx Visit 1 
Tx V1 FU1 
Tx V1 FU2 
Tx V1 FU3 
Tx V1 FU4 
Tx Visit 2 
Tx V2 FU1 
Tx V2 FU2 
Tx V2 FU3 
Tx V2 FU4 
Tx Visit 3 
Tx V3 FU1 
Tx V3 FU2 
Tx V3 FU3 
Tx V3 FU4 
Tx Visit 4 
Tx V4 FU1 
Tx V4 FU2 
Tx V4 FU3 
Tx V4 FU4 
90 Day 
Follow-up 
Visit 
135 Day 
Follow-up 
Visit 
EOS / ET 
Visitp 
Visit Windows (Days) 
(Day -28 to Day -1) 
Day 1 
1 to 2 Days After TV1 
3 to 5 Days After TV1 
6 to 9 Days After TV1 
10 to 14 Days After TV1 
Day 22 (±3 Days) 
1 to 2 Days After TV2 
3 to 5 Days After TV2 
6 to 9 Days After TV2 
10 to 14 Days After TV2 
Day 43 (±3 Days) 
1 to 2 Days After TV3 
3 to 5 Days After TV3 
6 to 9 Days After TV3 
10 to 14 Days After TV3 
Day 64 (±3 Days) 
1 to 2 Days After TV4 
3 to 5 Days After TV4 
6 to 9 Days After TV4 
10 to 14 Days After TV4 
Day 90 (±7 Days) 
Day 135 (±7 Days) 
Day 180 (±7 Days) 
Informed consenta 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Inclusion/Exclusion criteria 
review 
X 
Xb 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Clinician Reported 
Photonumeric Cellulite 
Severity Scale (CR-PCSS)c,d 
X 
Xb 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Hexsel Cellulite Severity 
Scale (CSS)c,d 
X 
Xb 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Cohort assignmente 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Medical and surgical historyf 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Cellulite history 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Physical examination 
(including height) 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Weight 
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
Fitzpatrick Skin Type d 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Vital signs 
X 
Xg 
  
  
  
  
Xg 
  
  
  
  
Xg 
  
  
  
  
Xg 
  
  
  
  
  
  
X 
Clinical laboratory tests 
(chemistry, hematology, 
urinalysis) 
X 
 
  
  
  
  
 
  
  
  
  
 
  
  
  
  
 
  
  
  
  
  
  
X 
Serum pregnancy test 
X 
 
  
  
  
  
 
  
  
  
  
 
  
  
  
  
 
  
  
  
  
  
  
X 
Urine pregnancy test 
  
Xh 
  
  
  
  
Xh 
  
  
  
  
Xh 
  
  
  
  
Xh 
  
  
  
  
  
  
  
Selection and marking of 
dimples to be treated within 
both buttocks 
  
Xh 
  
  
  
  
Xh 
  
  
  
  
Xh 
  
  
  
  
Xh 
  
  
  
  
  
  
  

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Activities 
Screening 
28 days 
Treatment Period 
90 days 
Follow-Up Period 
90 days 
Visit Number 
Screening 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
Visit 
Screening 
Tx Visit 1 
Tx V1 FU1 
Tx V1 FU2 
Tx V1 FU3 
Tx V1 FU4 
Tx Visit 2 
Tx V2 FU1 
Tx V2 FU2 
Tx V2 FU3 
Tx V2 FU4 
Tx Visit 3 
Tx V3 FU1 
Tx V3 FU2 
Tx V3 FU3 
Tx V3 FU4 
Tx Visit 4 
Tx V4 FU1 
Tx V4 FU2 
Tx V4 FU3 
Tx V4 FU4 
90 Day 
Follow-up 
Visit 
135 Day 
Follow-up 
Visit 
EOS / ET 
Visitp 
Visit Windows (Days) 
(Day -28 to Day -1) 
Day 1 
1 to 2 Days After TV1 
3 to 5 Days After TV1 
6 to 9 Days After TV1 
10 to 14 Days After TV1 
Day 22 (±3 Days) 
1 to 2 Days After TV2 
3 to 5 Days After TV2 
6 to 9 Days After TV2 
10 to 14 Days After TV2 
Day 43 (±3 Days) 
1 to 2 Days After TV3 
3 to 5 Days After TV3 
6 to 9 Days After TV3 
10 to 14 Days After TV3 
Day 64 (±3 Days) 
1 to 2 Days After TV4 
3 to 5 Days After TV4 
6 to 9 Days After TV4 
10 to 14 Days After TV4 
Day 90 (±7 Days) 
Day 135 (±7 Days) 
Day 180 (±7 Days) 
Digital photographyi 
X 
Xj 
X 
X 
X 
X 
Xj 
X 
X 
X 
X 
Xj 
X 
X 
X 
X 
Xj 
X 
X 
X 
X 
X 
X 
X 
QWO (CCH-aaes) 
administrationd 
(Investigational Buttock) 
  
  
  
  
  
  
Xk 
  
  
  
  
X 
  
  
  
  
X  
  
  
  
  
  
  
  
QWO (CCH-aaes) 
administrationd 
(Control Buttock) 
  
 X 
  
  
  
  
Xk 
  
  
  
  
X 
  
  
  
  
 
  
  
  
  
  
  
  
Dispensing of tranexamic 
acid  
 
 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tranexamic acid use 
 
 
 
 
 
 
 
D21, D22, D23, 
D24, D25 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Compliance check for 
tranexamic acid 
 
 
 
 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Collection of tranexamic acid  
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Investigator Assessment of 
Bruising Severity Scale 
(IABSS) d,l 
  
Xh 
X 
X 
X 
X 
Xh 
X 
X 
X 
X 
Xh 
X 
X 
X 
X 
Xh 
X 
X 
X 
X 
  
  
  
Investigator-Global Aesthetic 
Improvement Scale (I-GAIS) 
d,l,m 
  
  
  
  
  
  
Xh 
  
  
  
  
Xh 
  
  
  
  
Xh 
  
  
  
  
X 
X 
X 
Prior medicationsn 
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Concomitant 
medications/procedures 
Collect throughout the study 
Adverse eventso 
Collect throughout the study 

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a Performed prior to any study-required assessments. 
b Reassessed and verified prior to dosing. 
c CR-PCSS rating must be a ‘3’ (moderate) or ‘4’ (severe) on each buttock and the Hexsel CSS total score must be ≤ 12. 
d To be performed by a qualified designated physician. 
e Participants will be assigned to 1 of 7 cohorts using an interactive response technology (IRT) system. 
f Medical and surgical history will include a review of all medical history and surgical procedures completed in the prior 10 years and any surgery completed at any time in the 
treatment area. Tobacco and ethanol (EtOH) use will also be collected. 
g Vital signs (temperature, pulse, systolic blood pressure, and diastolic blood pressures) will be collected up to 2 hours prior to, and at 15 and 30 minutes after, QWO (CCH-aaes) 
administration on the days of treatment. Pulse and blood pressure will be collected after the participant has been sitting for 5 minutes. 
h Prior to treatment with QWO (CCH-aaes). 
i No manipulation of the treatment area should be done prior to any “before” images. 
j On the days of treatment, the buttocks will be photographed before and after injection site and dimple marking. 
k Participants will take tranexamic acid orally TID for 5 days (prior to the day of the second injection on Day 21, the day of the second injection (Day 22) and for the 3 days 
following the second injection (Day 23 to Day 25). Tranexamic acid use should be documented on the Tranexamic Acid Administration page of the eCRF. 
l Based on live assessments while the participant is in front of the investigator. Assessments will be performed for each buttock separately. 
m 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 during the live assessment. 
n Prior medications (other than QWO [CCH-aaes]) include medications taken 90 days before Screening. All prior QWO (CCH-aaes) use should be captured. 
o Serious adverse events (SAEs) and adverse events (AEs) will be collected by the investigator from the time of signing the informed consent through the Day 180 EOS/ET Visit. 
All ongoing AEs must be followed until they have resolved or for 28 days after the participant’s last treatment visit, whichever comes first. For participants who withdraw from 
the study early, SAEs and AEs will be collected for 28 days after the last dose of QWO (CCH-aaes). 
p Participants are encouraged to remain in the study for follow-up until the Day 180 Visit. Participants who discontinue from the study or study intervention and do not agree to 
remain in the study for follow-up until Day 180, will be asked to complete an early termination (ET) visit and a 28-day post-treatment Safety Follow-up Visit (or phone call if a 
visit is not possible) if applicable. The status of any ongoing AEs/SAEs or the occurrence of any new AEs/SAEs will be assessed. 
EOS = end of study; FU = follow-up; TID = three times daily; Tx = Treatment; V = visit 
 

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3. 
INTRODUCTION 
Collagenase clostridium histolyticum (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. 
3.1. 
Background 
Collagenases are proteinases that hydrolyze collagen in its native triple helical conformation 
under physiological conditions. To investigate the use of collagenases in the treatment of 
cellulite, Endo Pharmaceuticals Inc. (Endo) has developed a novel formulation of AUX-I and 
AUX-II referred to as CCH-aaes. CCH effectively lyses the subdermal located fibrous septae, the 
underlying cause of the skin dimpling in women with cellulite, at the site of injection. 
QWO (CCH-aaes) is approved for the treatment of moderate to severe cellulite in the buttocks of 
adult women. Approval was based on studies demonstrating an improvement in the severity of 
cellulite, as determined by both the investigator and the participant, in participants treated with 
QWO (CCH-aaes) administered at a dose of 0.84 mg per treatment area every 21 days for 3 
sessions. Across all previous studies, CCH has demonstrated an acceptable safety and 
immunogenicity profile. 
3.2. 
Rationale 
Although QWO (CCH-aaes) related post-injection bruising generally resolves within 21 days 
(CSR EN3835-302; CSR EN3835-303), and before the next treatment session, bruising is 
bothersome to participants due to the risk of potential skin discoloration and associated swelling 
and pain. Study EN3835-401 (MOBI) was a Phase 4, open-label study designed to assess the 
effects of mitigation treatments on bruising due to QWO (CCH-aaes) treatments on buttock 
cellulite after the first treatment with QWO. Mitigation treatments included a compression 
garment, instant cold packs, arnica (OcuMend®) Patches, laser treatment, and INhance Post-
Injection Serum with TriHex Technology®. Improvement in the severity of bruising when QWO 
(CCH-aaes) was administered with and without different mitigation treatments was assessed by 
the Investigator using the Investigator-Bruising Improvement Scale and the IABSS. Furthermore, 
participants also assessed the intensity of the temporal pattern of post-injection pain using an 
Injection Pain Assessment Scale. The safety of QWO (CCH-aaes) with mitigation treatment was 
also assessed.  
Consistent with the known effects of QWO (CCH-aaes), bruising was transient, mild to moderate 
in severity, and in most participants resolved before the next treatment session on Day 22. 
Injection site pain, 48-hours after QWO (CCH-aaes) injection, was also mild in severity. There 
were no differences among the mitigation treatment cohorts in the severity of bruising. In cohorts 
where only 1 buttock was treated with a mitigation strategy (ie, cold packs, OcuMend [arnica], 
INhance Post-Injection Serum, and pulse dye laser), there was no difference between the 
mitigation-treated buttock, and the buttock that did not receive mitigation treatment. Mitigation 
treatment also did not impact pain related to injection site bruising (CSR EN3835-401). It is 

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important to note that the labeled dose and concentration of QWO (0.84 mg administered at a 
concentration of 0.23 mg/mL) was administered consistently in the MOBI study. Alternate 
doses, concentrations, depth of injection or diluent additives were not used 
APHRODITE-1 will use different single and combination mitigation strategies to decrease the 
severity of bruising after QWO (CCH-aaes) injection. A description of the chemistry, 
pharmacology, efficacy, and safety of QWO (CCH-aaes) is provided in the QWO Prescribing 
Information. 
3.3. 
Benefit-Risk Assessment 
During this study, QWO (CCH-aaes) will be administered by a qualified designated physician 
using different doses, strengths (concentrations), diluent additives, depths of injection, and 
methods of injection to determine if these methods will decrease the extent, severity, and 
duration of bruising. The benefit and risk of each study intervention is described in this section. 
3.3.1. 
QWO (CCH-aaes) 
QWO is approved for the treatment of moderate to severe cellulite in the buttocks of adult 
women. The results of all Phase 2 and 3 studies conducted demonstrated a consistent effect of 
QWO (CCH-aaes) in reducing the severity of cellulite. The results of two Phase 3 pivotal 
efficacy studies (Studies EN3835-302 and EN3835-303) established the efficacy of CCH 
administration in the treatment of moderate to severe cellulite in the buttocks of adult women 
when injected subcutaneously at a dose of 0.84 mg per treatment area every 21 days for 
3 treatment visits. A treatment area was defined as a single buttock receiving up to 12 injections, 
0.3 mL each (up to a total of 3.6 mL), of QWO (CCH-aaes). Two treatment areas (2 buttocks) 
were treated at each visit.  
A reduction in the severity of cellulite was observed as assessed by validated assessment scales 
as early as 21 days after administration of the first treatment session of QWO (CCH-aaes) and 
was sustained throughout the 71-day double-blind study period. Furthermore, overall patient-
reported satisfaction, emotional impact, and visual appearance measures showed a greater and 
statistically significant improvement in the QWO (CCH-aaes) group over the placebo group. The 
TEAEs observed were predominantly localized injection site reactions that were nonserious, 
primarily mild to moderate in severity, transient, and decreased in frequency with each 
subsequent treatment session. Bruising was quite common, reported in 84% of subjects (QWO 
Prescribing Information). 
Further details about the known and expected risks and reasonably expected adverse events 
(AEs) can be found in the QWO prescribing information (QWO Prescribing Information). 
3.3.2. 
Lidocaine and Epinephrine 
Lidocaine is a local anesthetic that helps reduce pain or discomfort caused by invasive medical 
procedures such as needle punctures. Epinephrine has vasoconstriction properties that when 
combined with local anesthetics (ie, lidocaine) prolongs the localized action of lidocaine and 
results in local vasoconstriction. A total dose of 1260 to 2880 mg lidocaine corresponding to 
10.5 to 34.4 mg/kg was administered to patients undergoing lipectomy and was found to be safe 
(Samdal et al, 1994). Doses intended for use in this study are considerably lower (maximum of 
36 mg of lidocaine and 9 mcg epinephrine per dose). Epinephrine has been used in cosmetic 

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surgery extensively, such as a tumescent anesthetic in the majority of current-day liposuction 
procedures, and has been used to reduce intra-procedural bleeding and post-procedural bruising. 
Epinephrine causes vasoconstriction of surrounding vessels which can limit both bleeding and 
bruising and also inhibits activation of eosinophils that play a role in bruising (Funt and Pavicic, 
2013). 
While very rare, an allergic reaction to lidocaine may occur.  
3.3.3. 
Half-dose QWO (CCH-aaes) 
In Cohorts 1 and 5, half the labeled dose (0.42 mg) of QWO (CCH-aaes) will be administered to 
the investigational side to determine the extent to which dose may be associated with the severity 
of bruising. In Cohort 6, half the labeled dose (0.42 mg) of QWO (CCH-aaes) will be 
administered to the control side. A similar dose (0.48 mg) was implemented in Study  
AUX-CC-831, a small dose ranging study, where improvements were also observed in cellulite 
appearance at a dose of CCH 0.48 mg per region. Bruising and discoloration were reported at 
slightly numerically less than the labeled 0.84 mg also tested in that study. The AUX-CC-831 
study did not compare severity of bruising between doses tested.  
In Cohorts 1 and 5, the total dose administered to the participant in both the investigational side 
and the control side through the course of the study will be QWO (CCH-aaes) 3.78 mg (after 3 
treatment sessions each 21 days apart). Details regarding the total dose for Cohort 6 can be found 
in Section 3.3.4. The risk of half-dose of QWO (CCH-aaes) therefore is expected to remain 
consistent with the risks of the labeled dose of QWO (CCH-aaes).  
3.3.4. 
Quarter-dose QWO (CCH-aaes) 
In Cohort 6, one-quarter of the labeled dose (0.21 mg) at one-half of the labeled concentration 
(0.12 mg/mL) of QWO (CCH-aaes) will be administered to the investigational side. Half of the 
labeled dose (0.42 mg) at the labeled concentration (0.23 mg/mL) of QWO (CCH-aaes) will be 
administered to the control side. Cohort 6 will consist of 2 treatment sessions, 6 weeks apart. The 
total dose administered for Cohort 6 to the participant in both the investigational and control 
sides during the study will be QWO (CCH-aaes) 1.26 mg. The purpose of decreasing the 
dose/concentration and lengthening the interval between Treatment Session 1 (Day 1) and 
Treatment Session 2 (Day 43+ 3 days) is to determine whether there will be an improvement in 
both bruising and subsequent discoloration. 
3.3.5. 
2.5-Fold and 5-Fold Diluted Concentrations of QWO (CCH-aaes) 
A 5-fold dilution of QWO (CCH-aaes) was administered in Studies EN3835-209, EN3835-224, 
and EN3835-305. Administering QWO (CCH-aaes) using this dilution has been shown to be 
safe. In Study EN3835-224, a lower frequency of discoloration was observed using this 5-fold 
dilution. An approximate 2.5-fold dilution of QWO (CCH-aaes) representing approximately 40% 
of the labeled concentration will also be evaluated during this study (Cohort 4). Given that the 
same dose (0.84 mg) of QWO (CCH-aaes) will be administered using these concentrations, the 
benefit-risk profile is expected to remain consistent with the benefit-risk of the labeled dose of 
QWO (CCH-aaes). 

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3.3.6. 
Tranexamic Acid 
To date, this is the first company-conducted study of oral tranexamic acid to potentially reduce 
bruising associated with QWO (CCH-aaes) injections and as such its benefit is unknown. 
Tranexamic acid is a synthetic lysine amino acid derivative which competitively inhibits the 
activation of plasminogen to plasmin, resulting in inhibition of fibrinolysis. By inhibiting the 
formation of plasmin, a proinflammatory cell activator (Rorich and Cho, 2018), it acts as an anti-
inflammatory agent. Bruising is often caused by localized bleed that extravasates into the 
surrounding interstitial tissues. Based on its mechanism of action, it is thought that tranexamic 
acid may mitigate bruising associated with QWO (CCH-aaes). 
Tranexamic acid is indicated for menorrhagia (Tranexamic Acid Prescribing Information) at a 
dose of 1300 mg TID orally for 5 days during multiple cycles. It is widely used to prevent and 
treat blood loss in a range of situations such as heavy menstrual bleeding, dental procedures, and 
various surgeries including plastic surgery (Ockerman et al, 2021; Rorich and Cho, 2018). 
Tranexamic acid is also routinely used as an adjunct in aesthetic procedures to minimize 
swelling, ecchymosis and bruising (Mehdizadeh et al, 2018; Wokes et al, 2021). 
One of the more serious risks associated with tranexamic acid is an increased risk of vascular 
occlusive events. However, these appear to be rare. In a nationwide registry study from Denmark 
(Meaidi et al, 2021) 2 million women were followed for 13.8 million person-years. While the 
study found use of oral tranexamic acid to be positively associated with venous 
thromboembolism, the number needed to harm per 5 days of treatment was high, at 78,549 
women, which is unlikely to be seen in a study of this size. The registry study concluded that in a 
population of healthy women, venous thromboembolism and arterial thrombosis are very rare 
adverse events during short-lasting use of oral tranexamic acid, comparable to that of combined 
oral contraception. A systemic review and metanalysis (Taeuber et al, 2021) reached a similar 
conclusion regarding the association between intravenous tranexamic acid with thromboembolic 
events. After analyzing a total of 216 eligible trials including 125,550 patients, their findings 
showed no increased risk of thromboembolic events with tranexamic acid.  
While very rare, an allergic reaction to tranexamic acid may occur. To mitigate the risk of a 
hypersensitivity reaction, participants with a known hypersensitivity reaction to tranexamic acid 
will be excluded from study participation. 
While relatively safe for use in most women, to mitigate the risk of thromboembolic events strict 
inclusion/exclusion criteria and addition of combination hormonal contraceptives and hormonal 
therapies as prohibited medications have been implemented within the study design to assist in 
mitigating the risk of thromboembolic events. Participants will be instructed to inform their 
physician should they have visual or ocular symptoms, or signs of an allergic reaction.  
3.3.7. 
Summary of Benefit-Risk Assessment 
Based on assessment of the benefit-risks for the study interventions administered in each cohort, 
the benefit-risk assessment for this study remains favorable. 

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4. 
OBJECTIVES AND ENDPOINTS 
4.1. 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
• 
To assess the effects of interventions on 
bruising of the buttocks of participants with 
cellulite after the first treatment with QWO 
(CCH-aaes).  
• 
Cohorts 1 to 6: The proportion of participants 
whose left buttock (investigational side) 
demonstrates at least 1-level lower score 
versus the right buttock (control side) on the 
Investigator Assessment of Bruising Severity 
Scale (IABSS), at Visit 3, three to 5 days after 
initial QWO (CCH-aaes) injection. The IABSS 
is a 5-point scale ranging from 0-4, with 0 
indicating no bruising or almost none, and 4 
indicating very severe bruising. 
• 
Cohort 7a: The proportion of participants 
whose left buttock (investigational side), at 
Visit 3, demonstrates at least 1-level lower 
score versus the right buttock (control side), at 
Visit 8 on the Investigator Assessment of 
Bruising Severity Scale (IABSS). These visits 
are three to 5 days after initial QWO (CCH-
aaes) injection for each respective buttock. 
• 
Cohort 7b: The proportion of participants 
whose left buttock (investigational side), at 
Visit 8, demonstrates at least 1-level lower 
score versus the right buttock (control side), at 
Visit 3, on the Investigator Assessment of 
Bruising Severity Scale (IABSS). These visits 
are three to 5 days after initial QWO (CCH-
aaes) injection for each respective buttock.  
Secondary 
• 
To assess the effects of interventions on 
bruising of the buttocks of participants with 
cellulite after each treatment with QWO 
(CCH-aaes). 
• 
The proportion of participants whose left 
buttock (investigational side) demonstrates at 
least 1 level lower score versus the right 
buttock (control side) on the IABSS, by visit. 
The IABSS is a 5-point scale ranging from 0-4, 
with 0 indicating no bruising or almost none, 
and 4 indicating very severe bruising. 

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Objectives 
Endpoints 
• 
Cohorts 7a and 7b: The proportion of 
participants within each cohort (ie, 7a and 7b) 
whose left buttock (investigational side) 
demonstrates at least 1-level lower score 
versus the right buttock (control side), on the 
IABSS, by corresponding treatment visit by 
buttock (first dose of QWO [CCH-aaes] on the 
investigational buttock with tranexamic acid vs 
the first dose of QWO [CCH-aaes] without 
tranexamic acid on the control side; second 
dose of QWO [CCH-aaes] on the 
investigational buttock vs second dose of 
QWO [CCH-aaes] on the control side; third 
dose of QWO [CCH-aaes] on the 
investigational side vs third dose of QWO 
[CCH-aaes] on the control side); and at each 
follow up visit thereafter.  
• 
To assess the level of aesthetic improvement of 
cellulite after treatment with QWO (CCH-
aaes). 
• 
The proportion of participants with an 
improved (+1 or better) score on the 
Investigator-Global Aesthetic Improvement 
Scale (I-GAIS) by treatment area at Days 22, 
43, 64, 90, 135 and 180 Visits. The I-GAIS is a 
7-point scale ranging from +3 (very much 
improved) to -3 (very much worse). 
• 
To assess the safety of QWO (CCH-aaes) for 
each study intervention in participants with 
cellulite. 
• 
Proportion of participants reporting each 
treatment-emergent adverse events (TEAEs) 
throughout the study. 
• 
To assess the safety of QWO (CCH-aaes) in 
participants for each study intervention in 
participants with cellulite.  
• 
Proportion of participants reporting TEAEs of 
injection site reactions in the left buttock 
(investigational side) vs the right buttock 
(control side). 
Exploratory 
• 
 
 
 
  
• 
 
 
 
 
 
 
 
 

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Objectives 
Endpoints 
• 
 
 
 
 
 
 
 
 
 

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5. 
STUDY DESIGN 
5.1. 
Overall Design 
This is a Phase 2 open-label, self-controlled study to assess different interventions designed to 
reduce bruising following QWO (CCH-aaes) treatment of moderate to severe cellulite of the 
buttocks in adult females. The study is expected to enroll approximately 210 participants, with 
up to 30 participants allocated to each of 7 cohorts, such that up to 168 participants complete the 
study.  
The study will comprise a Screening Period, a Treatment Period, and a Follow-up Period. After 
the Screening Period, on Day 1, participants who meet study criteria will be assigned to 1 of 7 
study intervention cohorts using an interactive response technology (IRT) system (Table 1). 
Participants will receive QWO (CCH-aaes) in different doses, strengths (concentrations), diluent 
additives, depths of injection, and methods of injection in a split buttock arrangement, with the 
right buttock serving as the control, and the left buttock (investigational side) receiving a study 
intervention.  
Table 1: 
Study Intervention Cohorts 
Cohort 
N 
Study Interventions Tested 
Left Buttock – 
Investigational Side 
Right Buttock – 
Control Side 
Cohort 1 
30 
Labeled dose (0.84 mg/ control 
side) of QWO (CCH-aaes) vs 
half the labeled dose 
(0.42 mg/investigational side) 
Labeled injection technique 
(3 aliquots) using half the 
labeled dose (0.42 mg/ 
investigational side) but 
maintaining the labeled 
concentration (0.23 mg/mL). 
Labeled injection 
technique (3 aliquots) 
using the labeled dose 
(0.84 mg/control side) and 
concentration 
(0.23 mg/mL). 
Cohort 2 
30 
Labeled dose (0.84 mg/ 
buttock) and concentration of 
QWO (CCH-aaes) vs an 
~5-fold dilution of the labeled 
concentration 
Labeled injection technique 
(3 aliquots) using the labeled 
dose (0.84 mg/investigational 
side) but using a ~ 5-fold 
dilution (0.05 mg/mL) of the 
labeled concentration 
(0.23 mg/mL). 
Labeled injection 
technique (3 aliquots) 
using the labeled dose 
(0.84 mg/control side) and 
concentration 
(0.23 mg/mL). 
Cohort 3 
30 
Labeled dose (0.84 mg/ 
buttock) and concentration of 
QWO (CCH-aaes) at an 
injection depth of ½ inch vs 
¼ inch 
Labeled injection technique 
(3 aliquots) using the labeled 
dose (0.84 mg/investigational 
side) and concentration 
(0.23 mg/mL) but with an 
injection depth of ¼ inch. 
Labeled injection 
technique (3 aliquots) 
using the labeled dose 
(0.84 mg/area) and 
concentration 
(0.23 mg/mL). Labeled 
injection at labeled depth 
of ½ inch. 
Cohort 4 
30 
Labeled dose (0.84 mg/ 
buttock) and concentration of 
QWO (CCH-aaes) vs an 
~2.5-fold dilution of the labeled 
concentration AND a single 
aliquot at ¼-inch depth of 
injection (both buttocks) 
Labeled dose (0.84 mg/ 
investigational side) using an 
~2.5-fold dilution of the 
labeled concentration 
(0.09 mg/mL) but 
administering only a single 
aliquot at ¼-inch depth per 
injection administered as up to 
30 injections. 
Labeled dose (0.84 mg/ 
control side) and 
concentration 
(0.23 mg/mL) but 
administering only a single 
aliquot at ¼-inch depth per 
injection administered as 
up to 12 injections. 

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Table 1: 
Study Intervention Cohorts (Continued) 
Cohort 
N 
Study Interventions Tested 
Left Buttock – 
Investigational Side 
Right Buttock – 
Control Side 
Cohort 5 
30 
Labeled dose (0.84 mg/ control 
side) and concentration of 
QWO (CCH-aaes) vs half the 
labeled dose (0.42 
mg/investigational side) of 
QWO (CCH-aaes) with 
lidocaine 2% and epinephrine 
1:200,000 utilized as diluent 
additive. 
Labeled injection technique 
(3 aliquots) using half the 
labeled dose (0.42 mg/ 
investigational side) with 
lidocaine 2% and epinephrine 
1:200,000 as diluent additive. 
Labeled injection 
technique (3 aliquots) 
using the labeled dose 
(0.84 mg/control side) and 
concentration 
(0.23 mg/mL). 
Cohort 6 
30 
Half of the labeled dose 
(0.42 mg/control side) while 
maintaining the labeled 
concentration (0.23mg/mL) of 
QWO (CCH-aaes) vs one-
quarter of the labeled dose 
(0.21 mg/investigational side) 
at one-half the labeled 
concentration (0.12 mg/mL) 
with both the control and 
investigational sides receiving 
only 2 treatment sessions 
administered 6 weeks apart. 
Labeled injection technique 
(3 aliquots) using one-quarter 
of the labeled dose 
(0.21 mg/investigational side) 
at one-half the labeled 
concentration (0.12 mg/mL). 
Treatment sessions will be 
administered 6 weeks apart. 
Labeled injection 
technique (3 aliquots) 
using one-half the labeled 
dose (0.42 mg/control side) 
but maintaining the labeled 
concentration 
(0.23 mg/mL). Treatment 
sessions will be 
administered 6 weeks 
apart. 
Cohort 7a 
15 
Labeled dose (0.84 mg/side) 
and concentration 
(0.23 mg/mL) of QWO (CCH-
aaes) with oral tranexamic acid.  
Labeled dose (0.84 mg/side), injection technique, and 
concentration (0.23 mg/mL) of QWO (CCH-aaes) to both 
the investigational and control buttocks. 
Participants will take tranexamic acid 1300 mg orally acid 
three times a day (TID) for 5 days (on Day -1 [the day prior 
to the day of the first injection to the investigational side], on 
Day 1 [the day of the first injection] and for the 3 days after 
the first injection of QWO (CCH-aaes) to the investigational 
side on Days 2-4) during the first treatment session. 
Cohort 7b 
15 
Labeled dose (0.84 mg/side) 
and concentration 
(0.23 mg/mL) of QWO (CCH-
aaes) with oral tranexamic acid.  
Labeled dose (0.84 mg/side), injection technique, and 
concentration (0.23 mg/mL) of QWO (CCH-aaes) to both 
the investigational and control buttocks.  
Participants will take tranexamic acid 1300 mg orally TID 
for 5 days (on Day 21 [the day prior to the day of the first 
injection to the investigational side], on Day 22 [the day of 
the first injection], and for the 3 days following the first 
injection on Days 23-25) during the second treatment session. 
Investigational side will not receive QWO (CCH-aaes) during 
the first treatment session. 
All participants will receive QWO (CCH-aaes) throughout the study to both the investigational 
and the control sides. Enrolled participants assigned to Cohorts 1 and 5 will receive a maximum 
dose of up to 0.84 mg of QWO (CCH-aaes) on the control side and a maximum dose of up to 
0.42 mg of QWO (CCH-aaes) to the investigational side per treatment session (Days 1, 22, and 
43) for a maximum total dose of 3.78 mg. Participants assigned to Cohorts 2, 3, and 4 will 
receive a maximum dose of up to 0.84 mg of QWO (CCH-aaes) per treatment area (to the control 
and investigational sides) per treatment session (total maximum dose of 1.68 mg per treatment 

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session × 3 treatment sessions [Days 1, 22, and 43] for a maximum total dose of 5.04 mg). 
Participants in Cohort 6 will receive a maximum dose of up to 0.42 mg of QWO (CCH-aaes) on 
the control side and a maximum dose of up to 0.21 mg of QWO (CCH-aaes) on the 
investigational side per treatment session for 2 treatment sessions (Days 1 and 43) for a 
maximum total dose of 1.26 mg. All participants in Cohort 7 will receive a maximum dose of up 
to 0.84 mg of QWO (CCH-aaes) on the control side and a maximum dose of up to 0.84 mg of 
QWO (CCH-aaes) to the investigational side per treatment session × 3 treatment sessions for a 
maximum total dose of 5.04 mg. Participants in Cohort 7a will have the investigational side 
treated with QWO (CCH-aaes) on Days 1, 22, and 43 with the control side treated with QWO 
(CCH-aaes) on Days 22, 43 and 64. Treatment will be staggered for participants in Cohort 7b vs 
Cohort 7a. Participants in Cohort 7b will have the investigational side treated on Days 22, 43, 
and 64 and the control side treated on Days 1, 22, and 43. Tranexamic acid will be provided by 
the sponsor and self-administered by all participants enrolled in Cohort 7. Participants in Cohort 
7a will take tranexamic acid 1300 mg orally TID for 5 days (prior to the day of the first injection 
of QWO (CCH-aaes) of the investigational buttock (Day -1), the day of the first injection 
(Day 1). and for the 3 days following the first injection (Days 2 to 4). Participants in Cohort 7b 
will take tranexamic acid orally TID for 5 days (prior to the day of the second injection on 
Day 21, the day of the second injection (Day 22) and for the 3 days following the second 
injection (Day 23 to Day 25). 
Bruising will be observed throughout the study. In an effort to standardize the risk and scope of 
bruising, the investigational and control sides in Cohorts 1 and 5 should be treated with the same 
concentration, same number of injections, and same number of aliquots per injection, but at 
different doses per injection or addition of diluent additive. In Cohort 2, the investigational and 
control sides will be treated with the same dose and number of injections, but the concentrations 
will vary. In Cohort 3, the investigational and control sides will be treated with the same dose, 
aliquots per injection, and number of injections, but at different injection depths. In Cohort 4, the 
dose will remain consistent between buttocks, but the number of injections and concentration 
will vary between the investigational and control sides. In Cohort 6, the investigational and 
control sides will be treated with the same number of injections, the same number of aliquots per 
injection, and an extended treatment interval, but at different doses and concentrations. In 
Cohort 7, the investigational and control sides should be treated with the labeled dose, injection 
technique and concentration of QWO (CCH-aaes) during each treatment visit, but oral 
tranexamic acid will be given before and after the first treatment with QWO (CCH-aaes) for the 
investigational buttock.  
Participants will return to the site for 4 follow-up visits (1 to 2 days, 3 to 5 days, 6 to 9 days, and 
10 to 14 days) after each treatment of QWO (CCH-aaes), for additional evaluations and digital 
photography to monitor the severity of bruising. Digital photographs will be obtained using a 
standardized method at each visit throughout the study. The effect of the different QWO 
(CCH-aaes) doses, strengths (concentrations), diluent additives, depths of injection, and methods 
of injection on the severity of bruising will be assessed by the investigator using the IABSS. The 
investigators will be evaluating the left (investigational) and right (control) buttocks separately 
with the IABSS. To assess the effect of QWO (CCH-aaes) on the severity of cellulite (efficacy), 
the investigator will complete the I-GAIS. Each buttock will be evaluated independently.  
After completing the Treatment Period, participants will return for 3 follow-up visits at Days 90, 
135, and 180 (EOS Visit).  

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At the EOS visit, the investigator will complete the I-GAIS and safety assessments will be 
evaluated. The total duration of study participation, including the Screening (28 days), Treatment 
(90 days) and Follow-up Periods (90 days) is approximately 208 days.  
5.2. 
Scientific Rationale for 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) and diminishes after the 
second or third treatment sessions (CSR EN3835-205; CSR EN3835-302, CSR EN3835-303). In 
most participants, bruising typically resolves within 21 days. 
Given the prevalence of bruising after administration of QWO (CCH-aaes) there is an expressed 
interest in evaluating if modifications of dose, strength (concentration), diluent additives, and 
methods of administration associated with administration of QWO (CCH-aaes) can reduce or 
potentially diminish bruising post injection. 
To examine the effect of these interventions, the buttocks of participants will be treated in a split-
buttock manner. Each buttock will receive QWO (CCH-aaes); the right buttock will serve as a 
control and the left buttock will be treated with a study intervention designed to potentially 
decrease bruising. Among the study interventions (designed to decrease bruising) to be evaluated 
include using half the labeled dose (0.42 mg) of QWO (CCH-aaes) (Cohort 1); the labeled 
concentration (2.3 mg/mL) vs an approximate 5-fold diluted concentration (Cohort 2); the 
labeled dose and concentration at the labeled ½-inch depth of injection vs a shallower injection 
depth (¼ inch; Cohort 3); the labeled concentration vs a 2.5-fold diluted concentration while 
maintaining a shallower injection depth (¼ inch) as a common factor (Cohort 4); and the labeled 
dose and concentration vs half-dose QWO (CCH-aaes) (0.42 mg) with lidocaine and epinephrine 
as a diluent additive (Cohort 5); half the labeled dose (0.42 mg) of QWO (CCH-aaes) and one- 
quarter of the labeled dose (0.21 mg) at one-half the labeled concentration (0.12 mg/mL) of 
QWO (CCH-aaes) (Cohort 6). For Cohort 6, there will be 2 treatment sessions given 6 weeks 
apart. 
Support for the use of more dilute concentrations of QWO (CCH-aaes) is derived from Studies 
EN3835-209 and EN3835-224 (see Section 3.3.3). Support for half-dose and quarter-dose of 
QWO (CCH-aaes) is derived from Study AUX-CC-831 (see Section 3.3.5). Study AUX-CC-831 
tested QWO (CCH-aaes) at 0.06 mg, 0.48 mg, and 0.84 mg. The study demonstrated 
improvement in a variety of parameters with the 0.06 mg dose, and investigators determined that 
approximately 45% of participants had improvement in their cellulite, although it was not 
statistically significant. The 0.48 mg dose was associated with statistically significant 
improvements. Therefore, in this study, Cohort 6 will evaluate a QWO (CCH-aaes) dose between 
the lowest and the middle dose given in Study AUX-CC-831, to determine whether there will be 
a decrease in bruising while experiencing an improvement in cellulite. 
Administering QWO (CCH-aaes) using a shallower depth of injection (¼ inch) rather than the 
labeled depth (½ inch) injection is supported by the results of a study conducted by Whipple et al 
(2021). Using ultrasound, the investigators identified the depth of the fibrous septa causing 
cellulite and delineated their anatomical orientation. The average skin thickness in 92 buttock 
dimples was 0.28 cm and the depth of superficial fascia was 0.84 cm. A depth of a ¼-inch 

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(0.64-cm) injection would place the tip of the needle within the superficial subcutaneous tissue. 
The majority of fascial bands originate from the superficial fascia and therefore using a 
shallower depth of injection could facilitate the lysis of the causative bands while potentially 
avoiding more expanded vasculature when using a deeper injection. This approach is further 
supported by the method used in a subcision technique for cellulite, which uses a depth of 
0.06 cm to 0.10 cm (Green and Cohen, 2015).  
In Study EN3835-224, a more dilute concentration of QWO (CCH-aaes) was used to treat 
cellulite. In this study’s 2-aliquot cohort, a concentration of QWO (CCH-aaes) 0.05 mg/mL, 
combined with injecting QWO (CCH-aaes) at ¼-inch and ½-inch depths, was demonstrated to be 
safe and well-tolerated with a low incidence of discoloration. In this study (APHRODITE-1), 
Cohorts 2 (~5-fold dilution) and 4 (~2.5-fold dilution) will evaluate using lower concentrations 
of QWO (CCH-aaes). Cohort 3 will evaluate using a shallower depth of injection. Taken 
together, this study will attempt to isolate the impact of each of these variables on bruising. 
For Cohort 7 the labeled dose, concentration and depth will be used throughout the study, 
however, there will be 2 sub-cohorts (7a and 7b) each with asynchronous treatment sessions of 
QWO (CCH-aaes) and different timing of treatment with oral tranexamic acid.  
• For Cohort 7a, oral tranexamic acid will be provided by the sponsor and self-
administered by participants, before and after the investigational buttock receives the 
first dose of QWO (CCH-aaes) on Day 1. The control buttock will receive the first 
treatment of QWO (CCH-aaes) on Day 22 to allow for the systemic effects of oral 
tranexamic acid to dissipate.  
• For Cohort 7b, tranexamic acid will be provided by the sponsor and self-
administered, orally, by participants, before and after the investigational buttock 
receives the first dose of QWO (CCH-aaes), on Day 22. This corresponds to the 
second dose of QWO (CCH-aaes) for the control buttock. This allows for a treatment 
session of the control buttock (initial treatment) without the presence of oral 
tranexamic acid. 
Staggering administration of tranexamic acid with QWO (CCH-aaes) will allow for a 
comparison between the investigational and control buttocks within a cohort and between 
cohorts.  
• See Section 3.3.6 for the rationale for administration of tranexamic acid. 
The endpoints will evaluate the proportion of participants with a reduction (improvement) in 
bruising severity on the variable buttock receiving study intervention vs the control side, as 
reported by the investigator.  
5.2.1. 
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, ensuring the safety of clinical study participants is our primary 
concern. In addition, the integrity of data obtained from clinical studies must be ensured. 
To ensure participant safety and protect data integrity with Endo’s approval, Endo may allow 
remote visits for certain safety assessments. This is aligned with the FDA Guidance on Conduct 

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of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency 
(March 2020, updated 30 August 2021). 
Additionally, participants impacted by the health emergency will be allowed to continue in the 
study and complete assessments when the investigational sites re-open as follows: 
• A participant who had received any dose of QWO (CCH-aaes) in the study prior to an 
interruption will be allowed to continue in the study. 
5.3. 
Justification for Endpoints 
The primary endpoint, for Cohorts 1 to 6, will be the investigator’s assessment of bruising in 
each buttock based on observed, in-person assessments on the IABSS, at Visit 3, three to five 
days after the initial QWO (CCH-aaes) injection. This endpoint will be assessed after the first 
treatment visit since this is historically when bruising has been the most severe. For Cohorts 1-6 
this will occur at Visit 3.  
The primary endpoint for Cohort 7a is the proportion of participants whose left buttock 
(investigational side), at Visit 3, demonstrates at least 1-level lower score versus the right buttock 
(control side), at Visit 8 on the IABSS. The primary endpoint for Cohort 7b is the proportion of 
participants whose left buttock (investigational side), at Visit 8, demonstrates at least 1-level 
lower score versus the right buttock (control side), at Visit 3, on the IABSS. These visits are 
three to 5 days after initial QWO (CCH-aaes) injection for each respective buttock. 
For Cohorts 7a and 7b, similar to Cohorts 1 to 6, this endpoint will be assessed after the first 
treatment visit since this is historically when bruising is most severe. In Cohorts 1 to 6, for all 
endpoints and in Cohorts 7a and 7b, for all endpoints other than the primary endpoint, all 
participants enrolled in the study will serve as their own control, since the study is designed to 
evaluate the effect of using different doses, different concentrations, and different methods of 
injection for QWO (CCH-aaes) applied unilaterally to the investigational side. The bruising on 
the left-buttock (investigational side) will be compared to the right buttock (control side).  
The comparison of buttocks for the primary endpoint by visit for Cohorts 7a and 7b is shown in 
Figure 1. 

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Figure 1: 
Primary Endpoints for Cohorts 7a and 7b 
 
Given the staggered treatment with QWO (CCH-aaes) within cohorts to the investigational and 
control sides, additional within cohort comparisons can be made. A secondary endpoint is the 
proportion of participants within each cohort (ie, 7a and 7b) whose left buttock (investigational 
side) demonstrates at least 1-level lower score versus the right buttock (control side), on the 
IABSS, by corresponding treatment visit. Given the staggered timing of the first dose of QWO 
(CCH-aaes), an asynchronous comparison for each respective buttock within cohorts will be 
made. The comparison of buttocks is shown in Figure 2. 
Figure 2: 
Secondary Endpoints (Within Cohort Comparison) for Cohorts 7a and 7b 
 
 
 
 
 
 

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For Cohort 6, half the labeled dose (0.42 mg for the control side) and one-quarter of the labeled 
dose at one-half the labeled concentration (0.21 mg at a concentration of 0.12 mg/mL for the 
investigational side) will be administered as 2 treatment sessions, 6 weeks apart. This is to 
determine whether a decrease in the dose and concentration combined with lengthening the time 
between treatment administration will decrease bruising and subsequent discoloration (refer to 
Section 5.2 for additional information). 
For Cohort 7a and 7b, the labeled dose of QWO (CCH-aaes) will be administered. This is the 
first company sponsored study of tranexamic acid use to reduce bleeding due to QWO (CCH-
aaes) which is 1300 mg TID for 5 days. Tranexamic acid will be taken during a single treatment 
session to help evaluate the potential effect in reducing bruising during QWO administration. 
Tranexamic acid will only be given during the first treatment session for the investigational 
buttock. The systemic effects are not expected to persist into the subsequent treatment visit.  
5.5. 
End of Study Definition 
A participant is considered to have completed the study if the participant has completed the 
Day 180 visit.  
The end of the study is defined as the completion of the final assessment (Day 180) for the last 
participant enrolled in the study. 
6. 
SELECTION AND WITHDRAWAL OF PARTICIPANTS 
6.1. 
Participant Inclusion Criteria 
Diagnosis and Inclusion Criteria 
To be eligible to participate in the study, at the Screening Visit and on Day 1, participants must: 
Age and Sex 
1. Be female ≥ 18 and ≤ 60 years of age at the time of consent. 
Disease Characteristics 
2. Have a body mass index (BMI) of 18 to < 32 kg/m2 and intends to maintain stable body 
weight during the study (a variation of ≤10% from baseline body weight is permitted). 
3. Have both buttocks with a score of 3 or 4 (moderate or severe cellulite) as reported by the 
investigator using the CR-PCSS. 
4. Have a Hexsel Cellulite Severity Scale (CSS) Total Score of ≤ 12. 
5. Has a Fitzpatrick Skin Type of I-IV. 
Type of Participant 
6. Cohort 1 to 6: Be of nonchildbearing potential (history of hysterectomy, bilateral 
oophorectomy, bilateral tubal ligation, or postmenopausal with no history of menstrual 
flow in the 12 months prior to the Screening Visit); or, if of childbearing potential, be 

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nonpregnant, nonlactating and agree to use effective contraception when with a male 
partner for the duration of the study and for 28 days after any active treatment period. 
Acceptable forms of contraception include hormonal measures (oral contraceptive pills, 
contraceptive patch, contraceptive ring, and injections), intrauterine devices, double 
barrier method (condom plus diaphragm, condom or diaphragm plus spermicidal gel or 
foam), surgical sterilization of the male partner, and abstinence. Cohort 7: Combination 
hormonal contraceptives cannot be used. 
7. Be willing and able to comply with all protocol required visits and assessments, including 
photography.  
8. Be willing to apply sunscreen to the treatment areas before each exposure to the sun for 
the duration of the study (from the Screening Visit through the Day 180/Early 
Termination [ET] Visit).  
9. Be willing to avoid the use of tanning beds, tanning booths or tanning lamps as well as 
outdoor tanning for the duration of the study (from the Screening Visit through the 
Day 180/Early Termination Visit). 
10. Be a non-employee or non-family member of the sponsor or research staff conducting the 
study. 
Informed Consent 
11. Be adequately informed and understand the nature and risks of the study and be able to 
provide consent. 
6.2. 
Participant Exclusion Criteria 
A participant will be excluded from study participation if the participant: 
Medical Conditions 
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 keloid 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 participant’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. Is pregnant and/or is breast-feeding or plans to become pregnant and/or to breast-feed 
during the course of the study.  

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3. Has any of the following local conditions in the areas to be treated: 
a. History of lower extremity thrombosis or post-thrombosis syndrome. 
b. A current vascular disorder (eg, vasculitis, varicose veins, telangiectasia). 
c. Inflammation or active infection (including lesions that indicate an active infection). 
d. Active cutaneous alteration including, but not limited to, rash, eczema or psoriasis. 
e. A tattoo or other artificially inflicted body marker in the treatment area. 
f. A mole located within 2 cm of any injection site. 
Prior/Concomitant Therapy 
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, such as (clopidogrel [Plavix®], including aspirin) at any dose 
within 14 days of treatment. 
b. Anticoagulants, such as warfarin (Coumadin®); heparin analogues, or Factor Xa 
inhibitors, 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, 
gingko biloba, ginger, St John’s Wort, 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. Has received treatment with tranexamic acid within 30 days before treatment. 
5. Has used any of the following for the treatment of cellulite on either buttock within the 
specified timelines, or intends to use any of the following at any time during the study: 
a. Liposuction during the 12-month period before dosing with study intervention. 
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) during the 12-month period before 
injection of study intervention. 
c. Any investigational treatment for cellulite during the 12-month period before the 
injection of study intervention. 
d. Endermologie or similar treatments during the 6-month period before injection of 
study intervention. 
e. Creams (eg, Celluvera™, TriLastin®) and/or home therapies to prevent or mitigate 
cellulite during the 2-week period before injection of study intervention. 
6. Intends to initiate an intensive sport or exercise program during the study. 
7. Intends to initiate an intensive weight reduction program during the study. 
8. Intends to engage in strenuous activity within 48 hours of study intervention 
administration. 

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9. Has recently tanned or intends to tan (outdoors or indoors). This includes, but is not 
limited to, the use of any tanning products or tanning booths/beds/lamps during the study. 
10. Has a history of hypersensitivity or allergy to collagenase or any other excipient of CCH.  
11.  For Cohort 5: has a known history of hypersensitivity to local anesthetics of the amide 
type or a history of hypersensitivity to epinephrine. 
12. For Cohort 5: are concurrently receiving to certain drugs like nitrites, antibiotics, or 
anticonvulsants, or any other drug which increases the risk of methemoglobinemia. 
13. Has any condition(s) that, in the investigator’s opinion, might indicate the participant to 
be unsuitable for the study. 
Prior/Concurrent Clinical Study Experience 
14. Has participated in a previous investigational study of CCH (EN3835, QWO [CCH-
aaes]) or received any collagenase treatments at any time prior to treatment in this study 
for the treatment of cellulite of the buttocks.  
15. Has received treatment with any investigational product within 30 days (or 5 half-lives, 
whichever is longer) of the start of the Screening Visit or throughout the study. 
Additional Exclusion Criteria for Cohort 7 
In addition to the applicable aforementioned exclusion criteria, participants enrolling in Cohort 7 
will be excluded from study participation if the participant: 
Medical Conditions 
16. Has any of the following medical conditions: 
a. history of venous or arterial thromboembolism or current thromboembolic disease. 
b. history of or current renal impairment. 
c. serum creatinine concentration > 1.4 mg/dL at Screening. 
Prior/Concomitant Therapy 
17. Requires the following concomitant medications during the study and cannot discontinue 
these medications within the time specified before QWO (CCH-aaes) treatment: 
a. concurrently taking combination hormonal contraceptives. 
b. concurrently undergoing hormone replacement therapy. 
c. has a known history of hypersensitivity to tranexamic acid. 
d. is a current smoker of nicotine or cannabinoids. 
6.3. 
Lifestyle Considerations 
Participants will be instructed to refrain from strenuous exercise for 48 hours after each treatment 
with QWO (CCH-aaes) and will be instructed to not initiate intensive sports, exercise, or weight 
reduction programs during the study. 

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Participants should avoid medications, homeopathic supplements, or foods as advised by the 
qualified designated physician or designee prior to QWO (CCH-aaes) treatment. 
Participants should not use any tanning booth/beds/lamps, or tanning products during the study. 
Participants in Cohort 7 should avoid smoking (including vaping, nicotine, or marijuana 
cigarettes) during the study. 
6.4. 
Screen Failures 
Screening procedures will be conducted during the Screening Period (Day -28 to Day -1).  
Participants who do not meet all of the eligibility criteria will be deemed a screen failure and the 
following information must be recorded for all participants who are screen failures: 
• Demography (age, gender, race/ethnicity). 
• Reason for screen failure. 
• Which eligibility criterion was not met. 
• Any AEs (including SAEs) experienced by the participant. 
No participant can be rescreened during this study. 
7. 
STUDY INTERVENTION 
Study intervention comprises QWO (CCH-aaes) and different doses, different concentrations, 
and different methods of administration of QWO (CCH-aaes) including diluent additives 
designed to decrease bruising. 
7.1. 
Selection and Marking of Dimples 
To ensure that the non-interventional buttock can serve as a control, and that a similar level of 
injection site bruising may be expected, participants should have a similar number of dimples 
requiring treatment on each buttock. Participants in Cohorts 1, 2, 3, 5, and 6 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 following the first treatment session, 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. 
Participants in Cohort 7 can be treated with up to 12 injections of QWO (CCH-aaes) on each 
buttock. Dimples will only need to be marked on the days of treatment. In Cohort 7a, on Day 1 
only, the investigational buttock will be treated with QWO (CCH-aaes) and on Day 64 only the 
control buttock will be treated with QWO (CCH-aaes). On Days 22 and 43, both buttocks will be 
treated with QWO (CCH-aaes). In Cohort 7b, on Day 1, only the control buttock will be treated 
with QWO and on Day 64, only the investigational buttock will be treated with QWO (CCH-
aaes). On Days 22 and 43, both buttocks will be treated with QWO (CCH-aaes). 

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For treatment, a qualified designated physician will select up to 12 dimples within each treatment 
area (each buttock) that are well-defined, evident when the participant is standing, and suitable 
for treatment. 
For each dimple selected for treatment, a qualified designated physician 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 qualified designated 
physician will then use a surgical marker to circle each of the dimples selected for treatment. 
In Cohort 4, the investigational side will receive QWO (CCH-aaes) at a labeled dose (0.84 mg) 
using a 2.5-fold diluted concentration (0.09 mg/mL) for up to 30 injections. The investigator will 
adapt an injection site stencil, which will be transferred to the location of injection. The number 
of injections will be adjusted by the clinician to best address the clinical presentation and need 
for treatment. QWO (CCH-aaes) will be administered as a single aliquot at a ¼-inch depth per 
injection. The control side will receive QWO (CCH-aaes) at the labeled dose (0.84 mg/treatment 
area) and concentration (0.23 mg/mL) but administering only a single aliquot at ¼-inch depth per 
injection administered as 12 injections. 
7.2. 
Treatment Administration 
7.2.1. 
QWO (CCH-aaes) 
QWO (CCH-aaes) and the other study interventions to potentially decrease bruising will be 
provided by Endo. The dose and volume of QWO (CCH-aaes) and other study interventions are 
detailed in Table 2. The dose of tranexamic acid is provided in Table 3. 

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Table 2: 
Study Intervention (CCH-aaes) by Buttock  
Cohort and 
Treatment Area 
Dose per 
Each 
Injection 
Injection 
Volume per 
Each Injection 
Number of 
Injections at 
Each 
Treatment 
Visit 
Dose (mg) at 
Each 
Treatment 
Visit 
Injection 
Volume (mL) 
per Each 
Treatment 
Visit 
Concentration 
(mg/mL) 
Cohort 1 
Right Buttock 
(control side) 
CCH-aaes 
0.07 mg 
0.3 mL (given as 
three 0.1 mL 
aliquots) 
Up to 12 
Up to 0.84 mg 
Up to 3.6 mL 
0.23 mg/mL 
Cohort 1 
Left Buttock 
(investigational side) 
CCH-aaes 
0.035 mg 
0.15 mL (given as 
three 0.05 mL 
aliquots) 
Up to 12 
Up to 0.42 mg 
Up to 1.8 mL 
0.23 mg/mL 
 
Cohort 2 
Right Buttock 
(control side) 
CCH-aaes 
0.07 mg 
0.3 mL (given as 
three 0.1 mL 
aliquots) 
Up to 12 
Up to 0.84 mg 
Up to 3.6 mL 
0.23 mg/mL 
Cohort 2 
Left Buttock 
(investigational side) 
CCH-aaes 
0.07 mg 
1.5 mL (given as 
three 0.5 mL 
aliquots) 
Up to 12 
Up to 0.84 mg 
Up to 18 mL 
0.05 mg/mL 
 
Cohort 3 
Right Buttock 
(control side) 
CCH-aaes 
0.07 mg 
0.3 mL (given as 
three 0.1 mL 
aliquots) 
Up to 12 
Up to 0.84 mg 
Up to 3.6 mL 
0.23 mg/mL 
Cohort 3 
Left Buttock 
(investigational side) 
CCH-aaes 
0.07 mg 
0.3 mL (given as 
three 0.1 mL 
aliquots) 
Up to 12 
Up to 0.84 mg 
Up to 3.6 mL 
0.23 mg/mL 
 
Cohort 4 
Right Buttock 
(control side) 
CCH-aaes 
0.07 mg 
0.3 mL (given as 
one 0.3 mL 
aliquot) 
Up to 12 
Up to 0.84 mg 
Up to 3.6 mL 
0.23 mg/mL 
Cohort 4 
Left Buttock 
(investigational side) 
CCH-aaes 
0.028 mg 
0.3 mL (given as 
one 0.3 mL 
aliquot) 
Up to 30 
Up to 0.84 mg 
Up to 9 ml 
0.09 mg/mL 
 
Cohort 5 
Right Buttock 
(control side) 
CCH-aaes 
0.07 mg 
0.3 mL (given as 
three 0.1 mL 
aliquots) 
Up to 12 
Up to 0.84 mg 
Up to 3.6 mL 
0.23 mg/mL 
Cohort 5 
Left Buttock 
(investigational side) 
CCH-aaes 
0.035 mg 
0.15 mL (given as 
three 0.05 mL 
aliquots) 
Up to 12 
Up to 0.42 mg 
Up to 1.8 mL 
0.23 mg/mL 
Lidocaine 
2% and 
Epinephrine 
1:200,000 
36 mg 
Lidocaine 
9 mcg 
Epinephrine 
Lidocaine 
20 mg/mL 
Epinephrine 
5 mcg/mL 
 
Cohort 6  
Right Buttock 
(control side) 
CCH-aaes 
0.035 mg 
0.15 mL (given as 
three 0.05 mL 
aliquots) 
Up to 12 
Up to 0.42 mg 
Up to 1.8 mL 
0.23 mg/mL 
Cohort 6 
Left Buttock 
(investigational side) 
CCH-aaes 
0.018 mg 
0.15 mL (given as 
three 0.05 mL 
aliquots) 
Up to 12 
Up to 0.21 mg 
Up to 1.8 mL 
0.12 mg/mL 

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Table 2: 
Study Intervention (CCH-aaes) by Buttock (Continued) 
Cohort and 
Treatment Area 
Dose per 
Each 
Injection 
Injection 
Volume per 
Each Injection 
Number of 
Injections at 
Each 
Treatment 
Visit 
Dose (mg) at 
Each 
Treatment 
Visit 
Injection 
Volume (mL) 
per Each 
Treatment 
Visit 
Concentration 
(mg/mL) 
Cohort 7a 
Right Buttock 
(control side)a 
CCH-aaes 
0.07 mg 
0.3 mL (given as 
three 0.1 mL) 
aliquots) 
Up to 12 
Up to 84 mg 
Up to 3.6 mL 
0.23 mg/mL 
Cohort 7a  
Left Buttock 
(investigational side)b 
CCH-aaes 
0.07 mg 
0.3 mL (given as 
three 0.1 mL 
Up to 12 
Up to 84 mg 
Up to 3.6 mL 
0.23 mg/mL 
 
Cohort 7b 
Right Buttock  
(control side)c 
CCH-aaes 
0.07 mg 
0.3 mL (given as 
three 0.1 mL) 
aliquots) 
Up to 12 
Up to 84 mg 
Up to 3.6 mL 
0.23 mg/mL 
Cohort 7b 
Left Buttock  
(investigational side)d 
CCH-aaes 
0.07 mg 
0.3 mL (given as 
three 0.1 mL 
Up to 12 
Up to 84 mg 
Up to 3.6 mL 
0.23 mg/mL 
a The investigational side will be treated with QWO (CCH-aaes) on Days 1, 22, and 43.  
b The control side will be treated with QWO (CCH-aaes) on Days 22, 43, and 64. 
c The investigational side will be treated with QWO (CCH-aaes) on Days 22, 43, and 64.  
d The control side will be treated with QWO (CCH-aaes) on Days 1, 22, and 43. 
Table 3: 
Study Intervention (Tranexamic Acid) in Cohort 7 
Product Name 
Tranexamic acid 
Type 
Drug 
Dose Formulation 
Tablet 
Unit Dose Strengths 
650 mg 
Dose amount and Frequency 
2 × 650 mg tablets (1300 mg) orally TID × 5 days 
Route of Administration 
Oral 
Sourcing 
Provided centrally by sponsor 
Packaging and Labeling 
Product will be provided in bottles of 30 tablets each. 
7.2.2. 
Cohorts 1-5, Control Sides, QWO (CCH-aaes) – Labeled Dose and 
Concentration 
Dosage and Mode of Administration: For the control side, a dose of up to 0.84 mg of QWO 
(CCH-aaes) up to 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 with the exception of Cohort 4 in 
which a single 0.3 mL injection will be utilized) for a total dose of 1.68 mg. There will be 3 
treatment visits at intervals of approximately 21 days as described in schedule of assessments. 
All injections will be given at the labeled depth of ½ inch, except in Cohort 3 and 4, where 
injections will be given at a depth of ¼ inch. 
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 

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number of injections per buttock may differ among treatments. The number of injections 
administered to each buttock must be recorded. The volume and dose of injection at each 
treatment visit for each buttock will be prepared per the Pharmacy Manual and injected per the 
Injection Guide in the Study Operations Manual. 
7.2.3. 
Cohort 1, Investigational Side Only, QWO (CCH-aaes) – Half-dose of Labeled 
Concentration  
Dosage and Mode of Administration: For the investigational side, a dose of up to 0.42 mg of 
QWO (CCH-aaes) up to 1.8 mL will be administered as up to 12 subcutaneous injections 
(0.15-mL injection administered as three 0.05-mL aliquots per injection). There will be 3 
treatment visits at intervals of approximately 21 days as described in schedule of assessments. 
The volume and dose of injection at each treatment visit for each buttock will be prepared per the 
Pharmacy Manual and injected per the Injection Guide in the Study Operations Manual.  
7.2.4. 
Cohort 2, Investigational Side Only, QWO (CCH-aaes) – Labeled Dose ~5-fold 
Diluted Concentration  
Dosage and Mode of Administration: For the investigational side, a dose of up to 0.84 mg of 
QWO (CCH-aaes) in up to 18 mL will be administered as up to 12 subcutaneous injections 
(1.5-mL injection administered as three 0.5-mL aliquots per injection). There will be 3 treatment 
visits at intervals of approximately 21 days as described in schedule of assessments. The volume 
and dose of injection at each treatment visit for each buttock will be prepared per the Pharmacy 
Manual and injected per the Injection Guide in the Study Operations Manual.  
7.2.5. 
Cohort 3, Investigational Side Only, QWO (CCH-aaes) – Labeled Dose and 
Concentration at ¼-inch Depth  
Dosage and Mode of Administration: For the investigational side, a dose of up to 0.84 mg of 
QWO (CCH-aaes) up to 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 at a depth of ¼ inch) for a 
total dose of 1.68 mg. There will be 3 treatment visits at intervals of approximately 21 days as 
described in schedule of assessments. The volume and dose of injection at each treatment visit 
for each buttock will be prepared per the Pharmacy Manual and injected per the Injection Guide 
in the Study Operations Manual.  
7.2.6. 
Cohort 4, Investigational Side Only, QWO (CCH-aaes) – Labeled Dose ~2.5-fold 
Diluted Concentration at ¼-inch Injection Depth 
Dosage and Mode of Administration: For the investigational side, a dose of up to 0.84 mg of 
QWO (CCH-aaes) up to 9 mL will be administered as up to 30 subcutaneous injections (0.3-mL 
injection administered as one 0.3-mL aliquot per injection at a depth of ¼ inch) for a total dose 
of 1.68 mg. There will be 3 treatment visits at intervals of approximately 21 days as described in 
schedule of assessments. The volume and dose of injection at each treatment visit for each 
buttock will be prepared per the Pharmacy Manual and injected per the Study Operations 
Manual. 

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7.2.7. 
Cohort 5, Investigational Side Only, QWO (CCH-aaes) – Half-dose at a Labeled 
Concentration with Lidocaine 2% and Epinephrine 1:200, 000 as a Diluent 
Additive 
Dosage and Mode of Administration: For the investigational side, a dose of up to 0.42 mg of 
QWO (CCH-aaes) up to 1.8 mL will be administered as up to 12 subcutaneous injections 
(0.15-mL injection administered as three 0.05-mL aliquots per injection). There will be 3 
treatment visits at intervals of approximately 21 days as described in the Schedule of 
Assessments. The volume and dose of injection at each treatment visit for each buttock will be 
prepared per the Pharmacy Manual and injected per the Injection Guide in the Study Operations 
Manual. QWO (CCH-aaes).  
7.2.8. 
Cohort 6, Investigational Side Only, QWO (CCH-aaes) – Quarter-dose with 
One-Half Concentration and Two Treatment Sessions at Approximately 42 Days 
Between Visits 
Dosage and Mode of Administration: For the investigational side, a dose of up to 0.21 mg of 
QWO (CCH-aaes) up to 1.8 mL will be administered as up to 12 subcutaneous injections 
(0.15-mL injection administered as three 0.05-mL aliquots per injection). Half the standard 
concentration (0.12 mg/mL) will be used. 
There will be 2 treatment visits at an interval of approximately 42 days as described in Schedule 
of Assessments for Cohort 6. The volume and dose of injection at each treatment visit for each 
buttock will be prepared per the Pharmacy Manual and injected per the Injection Guide in the 
Study Operations Manual. 
7.2.9. 
Cohort 6, Control Side Only, QWO (CCH-aaes) – Half of the Labeled Dose 
(0.42 mg/control side) Using the Labeled Concentration (0.23 mg/mL) at 
Approximately 42 Days between Visits 
For the control side, a dose of up to 0.42 mg of QWO (CCH-aaes) up to 1.8 mL will be 
administered as up to 12 subcutaneous injections (0.15 mL injection administered as three 
0.05-mL aliquots per injection). The standard concentration (0.23 mg) will be used. 
There will be 2 treatment visits at an interval of approximately 42 days as described in the 
Schedule of Assessments for Cohort 6. The volume and dose of injection at each treatment visit 
for each buttock will be prepared per the Pharmacy Manual and injected per the Injection Guide 
in the Study Operations Manual. 
7.2.10. 
Cohort 7, Labeled Dose and Concentration of QWO (CCH-aaes) with 
Tranexamic Acid 
Dose and Mode of Administration: Cohorts 7a and 7b: For the control and investigational sides, 
a dose of up to 0.84 mg of QWO (CCH-aaes) up to 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).  
Cohort 7a:  
• The investigational side will be treated with QWO (CCH-aaes), on Days 1, 22, 
and 43.  

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• The control side will be treated with QWO (CCH-aaes) on Days 22, 43, and 64. 
• Tranexamic acid 1300 mg orally TID×5 days, prior to the day of the first injection, on 
the day of the first injection (Day 1), and for 3 days after the first injection (Days 2, 3, 
and 4). Tranexamic acid will be provided by the sponsor and self-administered by the 
participant. 
Cohort 7b: 
• The investigational side will be treated with QWO (CCH-aaes), on Days 22, 43, 
and 64.  
• The control side will be treated with QWO (CCH-aaes) on Days 1, 22, and 43. 
• Tranexamic acid 1300 mg orally TID×5 days, prior to the day of the first injection of 
QWO (CCH-aaes) (Day 21), on the day of the first injection (Day 22), and for 3 days 
after the first injection (Days 23, 24, and 25). Tranexamic acid will be provided by 
the sponsor and self-administered by the participant. 
7.2.11. 
Care Procedures After Injection 
NOTE: CCH is a foreign protein and investigators must be prepared to address and manage an 
allergic reaction should it occur. At the time of each injection, a 1:1,000 solution of epinephrine 
for injection, 50 mg diphenhydramine injection or a suitable equivalent, and oxygen must be 
available and the investigator and site staff must be familiar with their use.  
To evaluate the participant for possible immediate immunological AEs, the participant will 
remain in direct observation of medical personnel who are skilled in the management of an 
allergic reaction for 30 minutes after receiving the injections of the study interventions and until 
the participant exhibits no sign of an immunological or other clinically significant systemic or 
local AE. The participant’s vital signs must be stable before the participant can leave direct 
observation.  
7.2.12. 
Preparation/Handling/Storage/Accountability 
QWO (CCH-aaes) 0.92 mg, its diluent (4 mL), and lidocaine (2%) and epinephrine (1:200,000) 
will be supplied by the sponsor. Each vial of study intervention and diluent will be minimally 
labeled with contents, sponsor identification, storage, administration/use, and appropriate caution 
statements. QWO (CCH-aaes) and the diluent must be kept in a temperature-monitored 
refrigerator (2°C to 8°C) with locked access until used or returned to the sponsor (or designee).  
Tranexamic acid, oral tablets will be supplied by the sponsor. Tranexamic acid will also be 
labeled with contents, sponsor identification, storage, administration/use and appropriate caution 
statements. Each participant will receive 1 bottle containing 30 tablets of tranexamic acid 
650 mg oral tablets. Oral tranexamic acid can be stored at room temperature. 
The investigator or designee will confirm that appropriate temperature control conditions have 
been maintained for all study interventions received and that any discrepancies are reported and 
resolved prior to study intervention administration. 
Only participants enrolled in the study will receive study intervention and only authorized study 
staff will dispense study intervention. 

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In accordance with the International Council for Harmonisation (ICH) requirements, at all times 
the investigator will be able to account for all study intervention furnished to the study site. An 
accountability record will be maintained for this purpose. The investigator must maintain 
accurate records indicating dates and quantity of study intervention received, to whom it was 
administered (participant-by-participant accounting), and accounts of any study intervention 
accidentally or deliberately destroyed. 
Please refer to the Pharmacy Manual for complete information regarding study intervention 
preparation, handling, and storage.  
7.3. 
Measures to Minimize Bias 
This is an open label study, however, the study intervention for each participant will be assigned 
in a 1:1:1:1:1:1:1 ratio using an IRT.  
7.3.1. 
Interactive Response Technology 
The investigator or designee will utilize the IRT system to register participants at screening. 
Each participant’s unique identification (ID) number will be assigned by the IRT system and will 
be used to identify the participant for the duration of the study within all systems and 
documentation.  
If a participant is not eligible to receive study intervention, or should discontinue from the study, 
the participant ID number will not be reassigned to another participant. Specific instructions for 
the use of the IRT system will be included in the IRT User Manual. 
The investigator must maintain a participant master log linking the participant ID to the 
participant’s name. The investigator must follow all applicable privacy laws in order to protect a 
participant’s privacy and confidentiality. Information that could identify a participant will be 
masked on material received by the sponsor. 
7.4. 
Study Intervention Compliance 
Participants will only receive QWO (CCH-aaes) at the study site and all dosing information will 
be recorded for each participant at each visit. Drug inventory will be maintained in the IRT. Used 
drug and diluent vials and 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 9.5). 
For participants enrolled in Cohort 7a, tranexamic acid will be dispensed prior to the Day 1 visit. 
Participants will be expected to bring the bottle of tranexamic acid to follow up Visits 2 and 3 to 
conduct a compliance check. Participants will return the bottle of tranexamic acid at follow-up 
Visit 4. 
For participants enrolled in Cohort 7b, tranexamic acid will be dispensed prior to the Day 22 
Visits. Participants will be expected to bring the bottle of tranexamic acid to follow up Visits 7 
and 8 to conduct a compliance check. Participants will return the bottle of tranexamic acid at 
follow-up Visit 9. 

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7.5. 
Prior and Concomitant Medications and Procedures 
The start and stop date, dose, unit, frequency, route of administration, and indication for all prior 
medications (taken within the 90 days prior to the Screening Visit) will be recorded. All prior 
EN3835, CCH, XIAFLEX®, and QWO (CCH-aaes) use should be recorded.  
The start and stop date, dose, unit, frequency, route of administration, and indication for all 
concomitant (taken from the Baseline Visit through the Day 180 Visit) medications and nondrug 
therapies (eg, blood transfusions, oxygen supplementation, physical therapy, etc) received will 
be recorded. 
7.5.1. 
Prohibited Medications/ Procedures 
During the study, the following treatments are prohibited: 
• Antiplatelet medication, such as (clopidogrel [Plavix®], including aspirin) at any dose 
within 14 days of treatment. 
• Anticoagulants, such as warfarin (Coumadin®); heparin analogues, or Factor Xa 
inhibitors, within 14 days of treatment. 
• NSAIDs, such as ibuprofen (Motrin®, Advil®) and naproxen (Aleve®), 7 days before 
the study. 
• Any medications (eg, corticosteroids, certain antidepressants [eg, citalopram, 
fluoxetine], nutritional/homeopathic supplements [eg, fish oil, Vitamin E, omega 3, 
gingko biloba, ginger, St John’s Wort, 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. 
• Tranexamic acid within 30 days before treatment. 
• For participants allocated to Cohort 5, drugs associated with methemoglobinemia. 
• For participants allocated to Cohort 7, combination hormonal contraceptives and 
hormonal therapy received during the study. 
During the study, the following procedures are prohibited in the buttocks: 
• Liposuction during the 12-month period before dosing with study intervention. 
• Injections radiofrequency device treatments; laser treatment; buttock implant 
treatment; cryolipolysis or surgery during the 12-month period before injection of 
study intervention. 
• Any investigational treatment for cellulite during the 12-month period before the 
injection of study intervention. 
• Endermologie or similar treatments during the 6-month period before injection of 
study intervention. 
• Creams (eg, Celluvera™, TriLastin®) and/or home therapies to prevent or mitigate 
cellulite during the 2-week period before injection of study intervention. 

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If a prohibited medication or procedure is used during the study, all pertinent information will be 
recorded. The Sponsor must be informed to determine whether the participant can continue in the 
study. 
7.5.2. 
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. 
7.5.3. 
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. 
8. 
DISCONTINUATION FROM STUDY INTERVENTION AND 
STUDY WITHDRAWAL 
8.1. 
Discontinuation of Study Intervention 
In certain instances, it may be necessary for a participant to be permanently discontinued from 
study intervention (QWO [CCH-aaes]) by the investigator or the sponsor. Treatment may be 
discontinued at the discretion of the investigator for safety, behavioral, or compliance reasons. 
This is expected to be uncommon. 
Participants who request to discontinue study intervention will be encouraged to complete the 
remaining study visits and evaluations and provide any additional follow-up information as 
required by the study. Participants who discontinue from the study intervention and do not agree 
to remain in the study for follow-up, will be requested, (if applicable) to complete an ET visit 
and a 28-day post-treatment Safety Follow-up Visit (or phone call if a visit is not possible), if 
applicable. During this visit, the status of any ongoing AEs/SAEs, or the occurrence of any new 
AEs/SAEs will be recorded. 
The date of and reason for discontinuation of study intervention will be recorded. 
Participants who discontinue from study intervention at any time after the first dose of study 
QWO (CCH-aaes) will not be replaced. 
8.2. 
Participant Withdrawal from the Study 
• A participant may withdraw from the study at any time at her own request. A 
participant may be withdrawn at any time at the discretion of the investigator for 
safety, behavioral, or compliance reasons, which is expected to be uncommon. The 
date and reason for withdrawal will be recorded. 
• At the time of withdrawing from the study, if possible, an ET visit should be 
conducted, as shown in the Schedule of Assessments. See the Schedule of 
Assessments for data to be collected at the time of study withdrawal and follow-up 
and for any further evaluations to be completed. 

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• The participant will be permanently discontinued from the study intervention, and the 
study, at the time of withdrawal of consent. 
• If the participant withdraws consent for disclosure of future information, the sponsor 
may retain and continue to use any data collected before the withdrawal of consent. 
The date a participant withdraws and the reason for withdrawal will be recorded in the source 
documentation and the electronic case report form (eCRF). This information should be recorded 
in the source documentation and the eCRF. 
If a participant discontinues from the study, all end-of-study procedures should be conducted as 
detailed in Schedule of Assessments. The date a participant discontinues and the reason for 
discontinuation will be recorded in the source documentation and eCRF. If, however, a 
participant withdraws consent, no additional procedures are required except the collection of AE 
information at the Safety Follow-up Visit, 28 days after the last treatment. This information 
should be recorded in the source documentation and the eCRF.  
Participants who have been withdrawn from the study at any time after the first dose of QWO 
(CCH-aaes) will not be replaced. However, additional participants may be enrolled in a given 
cohort to ensure that the required number of evaluable participants in each cohort is achieved in 
the applicable analysis population. 
8.3. 
Lost to Follow-up 
A participant will be considered lost to follow-up if the participant repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
Participants lost to follow-up at any time after the first dose QWO (CCH-aaes) may be replaced.  
9. 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the schedule of assessments (Section 2.4). 
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 participant should continue study intervention and/or be withdrawn 
from the study. 
All screening evaluations must be completed and reviewed to confirm that potential participants 
meet all eligibility criteria. The investigator will maintain a screening log to record details of all 
participants screened and to confirm eligibility or record reasons for screen failure, as applicable. 
Procedures conducted as part of the participant’s routine clinical management and obtained 
before signing of the informed consent form (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. 

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9.1. 
Screening Assessments 
9.1.1. 
Medical and Surgical 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. 
Medical and surgical history will include a review of all medical history and surgical procedures 
completed in the prior 10 years and any surgery completed at any time in the treatment area. 
9.1.2. 
Physical Examination 
A limited physical examination will be conducted at the Screening visit and will include 
evaluation of height and weight and the following organ systems: lungs, heart, abdomen, and 
extremities. Weight will also be recorded at the Days 1 and 180/ET visits. 
All examinations will be performed by a qualified designated 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. 
9.1.3. 
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 qualified designated physician) will determine the 
Fitzpatrick skin type for all participants on Day 1. Only participants with a Fitzpatrick Skin level 
of I-IV will be included in the study. 
9.1.4. 
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 (Table 4). 
Participants must have a Hexsel CSS total score ≤ 12 to be included in the study. The Hexsel 
CSS Score will be assessed according to the time points on the Schedule of Assessments.  

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Table 4: 
Hexsel Cellulite Severity Scale 
A – Number of Evident Depressions 
0 = none/no depressions 
1 = a small amount: 1-4 depressions are visible 
2 = a moderate amount: 5-9 depressions 
3 = a large amount: 10 or more depressions 
B – Depth of Depressions 
0 = no depressions 
1 = superficial depressions 
2 = medium depth depressions 
3 = deep depressions 
C – Morphological Appearance of Skin 
Surface Alterations 
0 = no raised areas 
1 = ‘orange peel’ appearance 
2 = ‘cottage cheese’ appearance 
3 = ‘mattress’ appearance 
D - Grade of laxity, flaccidity, or sagging 
skin 
0 = absence of laxity, flaccidity, or sagging skin 
1 = slight draped appearance 
2 = moderate draped appearance 
3 = severe draped appearance 
E – Current classification scale based on 
the scale originally described by 
Nürnberger and Müller (1978) 
0 = Grade or Stage 0 = There is no alteration of the skin surface. 
1 = Grade or Stage I = The skin of the affected area is smooth while 
the participant is standing or lying, but the alterations to the skin 
surface can be seen by pinching the skin or with muscle 
contraction. 
2 = Grade or Stage II = The orange skin or mattress appearance is 
evident when standing, without the use of any manipulation (skin 
pinching or muscle contraction). 
3 = Grade or Stage III = The alterations described in Grade or 
Stage II are present together with raised areas and nodules. 
9.1.5. 
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 validated 5-level photonumeric scale developed specifically for 
investigators and used by the investigator to assess the severity of the participant’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 
participant is in the standing position with relaxed gluteus muscles. Investigators who are 
physicians will be trained and qualified in the use of the CR-PCSS-prior to assessing any 
participants. 
Participants must have a baseline CR-PCSS rating of ‘3’ (moderate) or ‘4’ (severe) on each 
buttock at the Screening Visit to be included in the study. 

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9.2. 
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 participant safety and protect data integrity, Endo, in accordance with the FDA 
Guidance on Conduct of Clinical Trials of Medical Products During the COVID-19 Public 
Health Emergency (March 2020, updated 30 August 2021), will allow remote visits for certain 
efficacy assessments. Additionally, participants impacted by the health emergency will be 
allowed to continue in the study and complete remaining assessments when the investigational 
sites re-open. 
9.2.1. 
Digital Photography 
At the time points indicated on the schedule of assessments, the investigator or qualified 
designee will photograph bilateral buttocks and each buttock individually while the participant is 
standing in a consistent, standard relaxed pose, with relaxed gluteus muscles using the supplied 
Canfield camera system. 
Buttocks will be photographed at the following time points: 
• Cohorts 1-6: Before and after marking the dimples and injection sites on Days 1, 22, 
and 43. 
• Cohort 7: Before and after marking the dimples and injection sites on Days 1, 22, 43, 
and 64. 
• During the treatment and follow-up visits designated in the Schedule of Assessments.  
• For Cohort 4, photographs will be taken before and after marking the treatment areas. 
Photographs will include pre-marking images, and post-marking images delineating 
the perimeter of areas to be injected inclusive of injection site stencil. 
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, corporate communication, marketing, regulatory purposes, and/or legal 
applications as required/desired by Endo. 
Digital photographs captured by the investigator will be uploaded to a web-based repository 
using the Canfield camera system. Further information is provided in the Photography Manual in 
Study Operations Manual.  
9.2.2. 
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 

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3 = Severe bruising 
4 = Very severe bruising 
The severity of bruising will be documented on the bruising page of the eCRF. 
9.2.3. 
Investigator-Global Aesthetic Improvement Scale 
At the time points indicated in the Schedule of Assessments, the investigator will determine the 
degree of improvement of each buttock by comparing treated cellulite dimples from the Day 1 
pre-treatment (Baseline) digital image of each buttock to the treated dimples observed in a live 
assessment (Table 5). For each buttock, the investigator will provide the rating from those below 
that best represents his/her answer. 
Table 5: 
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 
9.3. 
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 participant safety and protect data integrity, Endo, in accordance with the FDA 
Guidance on Conduct of Clinical Trials of Medical Products During the COVID-19 Public 
Health Emergency (March 2020, updated 30 August 2021), will allow remote visits for certain 
safety assessments. Additionally, participants impacted by the health emergency will be allowed 
to continue in the study and complete remaining assessments when the investigational sites re-
open. 
9.3.1. 
Vital Signs 
For Cohorts 1-7, vital signs (temperature, pulse, systolic blood pressure, and diastolic blood 
pressures) will be collected up to 2 hours prior to, and at 15 and 30 minutes after, QWO (CCH-
aaes) administration on Days 1, 22, and 43. For Cohort 7, vital signs will also be collected on 
Day 64. Pulse and blood pressure will be collected after the participant has been sitting for 
5 minutes. 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). 

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9.3.2. 
Pregnancy Testing 
All female participants of childbearing potential will have serum and/or urine pregnancy tests at 
the time points outlined in the Schedule of Assessments. Results must be available prior to QWO 
(CCH-aaes) administration. Participants with positive results at the Screening Visit or on Day 1 
will be ineligible for study entry. Any female participant that becomes pregnant during the study 
will be immediately withdrawn from treatment and will have the pregnancy reported as per 
Section 9.4.5. 
For all female participant of childbearing potential, the participant’s agreement to use 
contraception throughout their study participation (Screening Visit through the Day 180 Visit, or 
for a minimum of 28 days after the last dose of study intervention for participants who terminate 
early) will be documented.  
9.3.3. 
Clinical Laboratory Determinations 
At the time points listed in the Schedule of Assessments, clinical laboratory tests will be 
conducted. Required clinical laboratory tests are outlined in Section 11.2. Clinical laboratory 
tests will be performed by a designated central laboratory. Each site will be provided with 
instructions on specimen collection, preparation, packaging, and transport. The results of the 
tests will be returned to the investigational sites. 
Samples for laboratory testing may be collected under fasted or nonfasted conditions. Fasting 
early morning samples are preferred, but a random daytime sample is acceptable. The date and 
time of the sample collection must be documented in the laboratory report. Investigators must 
review and sign laboratory reports and document the clinical significance of each laboratory 
abnormality. New clinically significant laboratory abnormalities or clinically significant changes 
in laboratory values will be reported as AEs (or SAEs, if appropriate). 
Clinical laboratory test data will be reviewed by the investigator, or qualified designated 
physician, and additional clinical laboratory tests may be ordered at his/her discretion (eg, if the 
results of any clinical laboratory test falls outside the reference range or clinical symptoms 
necessitate additional testing to ensure safety). Any additional testing will be performed by the 
designated central laboratory if needed to ensure participant safety. 
9.4. 
Adverse Events and Serious Adverse Events 
The definitions of AEs and SAEs can be found in Section 11.3. 
All AEs, including both observed or volunteered problems, complaints, signs or symptoms must 
be recorded, regardless of whether associated with the use of study intervention. Study 
intervention includes QWO (CCH-aaes) at the labeled dose and at different strengths 
(concentrations), diluent additives, depths of injection, and method of injection. This would 
include AEs resulting from concurrent illness, reactions to concurrent medication use, or 
progression of disease states (excluding the disease under study). A condition present at baseline 
that worsens after initiation of study intervention 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. 

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9.4.1. 
Time Period and Frequency for Collecting Adverse Event and Serious Adverse 
Event Information 
SAEs and AEs will be collected by the investigator from the time of signing the informed 
consent through the Day 180 EOS/ET Visit. 
Participants are encouraged to remain in the study for follow-up until the Day 180 Visit. 
Participants who discontinue from the study or study intervention and do not agree to remain in 
the study for follow-up until Day 180, will be asked to complete the 28-day post-treatment 
Safety Follow-up Visit (or phone call if a visit is not possible), if applicable. The status of any 
ongoing AEs/SAEs or the occurrence of any new AEs/SAEs will be determined. 
Investigators are not obligated to actively seek AEs and SAEs after conclusion of study 
participation. However, if the investigator learns of any SAE, including death, at any time after 
the participant has been discharged from the study, and the investigator considers the event to be 
reasonably related to the study intervention or study participation, the investigator must notify 
the sponsor within 24 hours as described in Section 11.3.4.1. 
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 11.3. 
9.4.2. 
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 participant is the preferred method to inquire about AE 
occurrences. 
At each visit, participants will be queried regarding any AEs that have occurred since the last 
visit. Study site personnel will then record all pertinent information. The study intervention 
compliance record should also be reviewed to detect potential intentional or unintentional 
overdoses. 
In addition, investigators will document observed and elicited AE. 
9.4.3. 
Follow-up of Adverse Events and Serious Adverse Events 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All ongoing AEs must be followed until they have resolved or for 
28 days after the participant’s last dose of study intervention, 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 11.3. 
9.4.4. 
Regulatory Reporting Requirements for Serious Adverse Events 
Prompt notification by the investigator to the sponsor of an SAE due to QWO (CCH-aaes) or 
other study interventions is essential so that legal obligations and ethical responsibilities 
regarding the safety of the study intervention 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 intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements regarding safety reporting to 
regulatory authorities, Institutional Review Boards (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. The Reference Safety Information for this study is the QWO 
Prescribing Information. 
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. 
9.4.5. 
Pregnancy 
All pregnancies in participants 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 
intervention in participants who terminate from the study early, must be reported, followed to 
conclusion, and the outcome reported, even if the participant 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 11.3). Spontaneous miscarriages should also be reported and handled as 
SAEs. 
Participants will be instructed to immediately notify the investigator of any pregnancies. 
A participant who becomes pregnant must be withdrawn from the study. Should a participant 
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 
participant discontinues treatment because of pregnancy. 
9.5. 
Treatment Overdose 
Study intervention overdose is any accidental or intentional use of treatment in an amount higher 
than the dose indicated by the protocol for that participant. Study intervention 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 intervention eCRF. 

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An overdose is not an AE per se, however all AEs associated with an overdose should both be 
entered on the AE eCRF and reported using the procedures detailed in Section 11.3, 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. 
10. 
STATISTICAL CONSIDERATIONS AND METHODS 
10.1. 
Sample Size Determination 
The proposed sample size is approximately 210 participants. The sample size is based on 
evaluation of the different study interventions in 7 cohorts of up to 30 participants each, such that 
up to 168 participants complete the study. 
10.2. 
Populations for Analysis 
For the purposes of analysis, the following populations are defined: 
The Safety Population is defined as all participants who received at least 1 injection of QWO 
(CCH-aaes). All safety analyses will be based on this population.  
The Full Analysis Set is defined as all participants in the Safety Population who have at least 1 
valid IABSS assessment at a treatment area after an injection of QWO (CCH-aaes). All efficacy 
analyses will be based on this population. 
10.3. 
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. 
10.3.1. 
Efficacy Analysis 
The primary endpoint for Cohorts 1-6: the proportion of participants whose left buttock 
(investigational side) demonstrates at least a 1-level lower score versus the right buttock (control 
side) on the IABSS, at Visit 3 will be summarized by cohort using appropriate descriptive 
statistics. In addition, the counts and percentages for each severity scale will be summarized by 
cohort and treatment area. 
The primary endpoint for Cohort 7a: The proportion of participants whose left buttock 
(investigational side), at Visit 3, demonstrates at least 1-level lower score versus the right buttock 
(control side), at Visit 8 on the IABSS will be summarized by cohort using appropriate 
descriptive statistics. In addition, the counts and percentages for each severity scale will be 
summarized by cohort and treatment area. 
The primary endpoint for Cohort 7b: The proportion of participants whose left buttock 
(investigational side), at Visit 8, demonstrates at least 1-level lower score versus the right buttock 
(control side), at Visit 3, on the IABSS will be summarized by cohort using appropriate 

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descriptive statistics. In addition, the counts and percentages for each severity scale will be 
summarized by cohort and treatment area. 
For Cohorts 1-6, at each visit the proportion of participants whose left buttock (investigational 
side) demonstrates at least a 1 level lower score versus the right buttock (control side) on the 
IABSS will be summarized by cohort using appropriate descriptive statistics. In addition, the 
counts and percentages for each severity scale at each visit will be summarized by cohort and 
treatment area. 
For Cohorts 7a and 7b: The proportion of participants whose left buttock (investigational side) 
demonstrates at least 1-level lower score versus the right buttock (control side), on the IABSS 
will be summarized by cohort using appropriate descriptive statistics at the corresponding 
treatment visit (first dose of QWO [CCH-aaes] on the investigational buttock with tranexamic 
acid vs the first dose of QWO [CCH-aaes] without tranexamic acid on the control side; second 
dose of QWO [CCH-aaes] on the investigational buttock vs second dose of QWO [CCH-aaes] on 
the control side; third dose of QWO [CCH-aaes] on the investigational side vs third dose of 
QWO [CCH-aaes] on the control side); and at each follow up visit thereafter. 
The proportion of participants with an improved (+1 or better) score as reported by investigators 
on the I-GAIS will be summarized by treatment area and by cohort at each visit. The I-GAIS is a 
7-level scale ranging from +3 (very much improved) to -3 (very much worse). 
10.3.2. 
Safety Analyses 
The safety parameters will include AEs, laboratory evaluations, and vital signs. 
10.3.2.1. Adverse Events 
AEs will be coded using MedDRA by preferred term (PT) within each system organ class 
(SOC). All TEAEs will be summarized by cohort for each SOC and PT. A participant will only 
be counted once per SOC and PT. All summary tables will include number of occurrences of the 
TEAEs and the number and percent of participants that experienced the TEAEs. 
In addition, for TEAEs of the injection site, the following variables will be summarized by 
cohort and treatment area for each SOC and PT: the number of occurrences of the TEAEs, the 
number and percent of participants that experienced the TEAEs, severity, and duration of the 
TEAEs. 
Only TEAEs will be included in all summaries, and all AEs will be listed.  
10.3.2.2. Clinical Laboratory Tests and Vital Signs 
The actual values and their changes from baseline for laboratory evaluations and vital signs will 
be summarized by cohort and visit (if applicable) using appropriate descriptive statistics. 

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11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
11.1. 
Appendix 1: Regulatory, Ethical and Study Oversight 
Considerations 
11.1.1. 
Regulatory and Ethical Considerations 
This clinical study is designed to comply with the ICH Guidance on General Considerations for 
Clinical Trials (62 FR 6611, December 17, 1997), Nonclinical Safety Studies for the Conduct of 
Human Clinical Trials for Pharmaceuticals (62 FR 62922, November 25, 1997), Good Clinical 
Practice: Consolidated Guidance (62 FR 25692, May 9, 1997) and 21 CFR parts 50, 54, 56 and 
312. 
The study will be conducted in full compliance with ICH E6 (R2), 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 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 ICF, advertisements, materials being provided to participants, and 
amendments (if any) will be approved by 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 local IRB with a copy of the current QWO Prescribing Information and the current 
Tranexamic Acid 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. 
Any amendment to this protocol will be provided to the investigator in writing by the Sponsor. 
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 participant, 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 participant, and must be immediately reported to the Sponsor. 
The investigator will be responsible for supplying updated safety and/or study information to 
study participants as it becomes available. 
11.1.2. 
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 

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certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after the completion of the study. 
11.1.3. 
Informed Consent Process 
The ICF must be approved by the sponsor and the IRB before any participant 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 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 participant the objectives of the exploratory research. Participants 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 
participant's agreement to allow any remaining specimens to be used for exploratory research. 
Participants 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), participants 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), 
participants 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. 
Participants 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. Participants will be made aware that they may 
withdraw from the study at any time for any reason. 
All versions of each participant'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 participant. 
The participants 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 participant 
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. 
11.1.4. 
Data Protection 
Study participants will be assigned a unique identifier by the sponsor or designee. Any 
participant records or datasets that are transferred to the sponsor will contain the identifier only; 
participant names or any information which would make the participant identifiable will not be 
transferred. 

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The participant 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 participant. 
The participant 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. 
11.1.5. 
Dissemination of Clinical Study Data 
Aggregate results data will be provided to the sites that actively enrolled participants into this 
study after the clinical study report is finalized. 
Study results and de-identified individual participant data will be released as required by local 
and/or national regulations. 
11.1.6. 
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 (R2) 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. 
11.1.7. 
Source Documents 
All participant information recorded in the eCRF will be attributable to source data from the 
investigational site unless otherwise outlined in this protocol. 

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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, 
participant diaries, data recorded in automated instruments, microfilm or magnetic media, and 
pharmacy records, etc. At a minimum, all data required to be collected by the protocol should 
have supporting source documentation for entries in the eCRF, unless the protocol specifies that 
data can be recorded directly on/in the eCRF or other device. 
The investigator shall retain and preserve a copy of all data collected or databases generated in 
the course of the study, specifically including but not limited to those defined by GCP as 
essential. Essential documents should be retained until at least 3 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or at least 3 years have elapsed since the formal discontinuation of 
clinical development of the investigational medicinal product. These documents should be 
retained for a longer period, however, if required by the applicable regulatory requirements or by 
an agreement with the sponsor. It is the responsibility of the sponsor to inform the 
investigator/institution as to when these documents no longer need to be retained. Prior to 
destruction of any study essential documents, the investigator must first obtain written approval 
from the sponsor. 
11.1.8. 
Study and Site Closure 
The sponsor has the right to suspend or terminate the study or a cohort in the study at any time. 
The study may be suspended or terminated for any reason. 
11.1.9. 
Publication Policy 
All data generated in this study are the property of Endo. 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. 

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11.2. 
Appendix 2: Clinical Laboratory Tests 
Hematology 
Biochemistry 
Urinalysis 
Hemoglobin 
Hematocrit 
Red blood cell (RBC) count 
Platelets 
White blood cell (WBC) count 
WBC Differential 
Prothrombin time (PT)/ 
International Normalized Ratio 
(INR) 
Glucose 
Sodium 
Potassium 
Calcium 
Chloride 
Carbon dioxide (CO2) 
Blood urea nitrogen (BUN) 
Creatinine 
Aspartate aminotransferase (AST) 
Alanine aminotransferase (ALT) 
Gamma-glutamyl transferase (GGT) 
Total bilirubin (direct bilirubin reflex if elevated)  
Albumin 
Alkaline phosphatase (ALP) 
Total protein 
Glucose 
Protein 
Specific gravity 
pH 
Ketones 
Bilirubin 
Urobilinogen 
Nitrite 
Blooda 
Leukocytesa 
a Microscopic examination will be performed if blood or leukocytes are detected by dipstick 

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11.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up and Reporting 
11.3.1. 
Definitions 
An AE is any unfavorable or unintended change in body structure (signs), body function 
(symptoms), laboratory result (eg, chemistry, ECG, X-ray, etc), or worsening of a preexisting 
condition associated temporally with the use of the study intervention whether or not considered 
related to the study intervention. Note: Any medical condition or laboratory abnormality already 
present at screening or baseline should be reported as medical history. If the medical condition 
present at baseline changes in severity or seriousness at any time during the study, it should be 
reported as an AE. AEs will be captured once a participant has signed the informed consent. AEs 
include: 
• Changes in the general condition of the participant. 
• Subjective symptoms offered by or elicited from the participant. 
• Objective signs observed by the investigator or other study personnel. 
• All concurrent diseases and/or medical occurrences 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 intervention 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 participant using the study 
intervention 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 participant 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 

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or convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
11.3.2. 
Relationship to Study Intervention  
In this study, study intervention will comprise QWO (CCH-aaes), and administration of QWO 
(CCH-aaes) at different doses, strengths (concentrations), diluent additives, depths of injection, 
and method of injection. 
The degree of “relatedness” of the AE to the study intervention must be described using the 
following scale: 
• Not related indicates that the AE is definitely not related to the study intervention. 
• Unlikely related indicates that there are other, more likely causes and study 
intervention is not suspected as a cause. 
• Possibly related indicates that a direct cause and effect relationship between study 
intervention 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 intervention. 
• Probably related indicates that there is evidence suggesting a direct cause and effect 
relationship between the AE and the study intervention. 
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. 
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. 
11.3.3. 
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 participant’s daily activities. 
• Moderate AEs introduce a low level of inconvenience or concern to the participant 
and may interfere with daily activities but are usually ameliorated by simple 
therapeutic measures. 
• Severe AEs interrupt a participant’s usual daily activity and typically require 
systemic drug therapy or other treatment. 
11.3.4. 
Reporting Adverse Events and Serious Adverse Events 
11.3.4.1. Reporting Adverse Events 
Throughout the study, AEs will be documented on the source document and on the appropriate 
page of the eCRF whether or not considered treatment-related. 

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11.3.4.2. Reporting Serious Adverse Events 
Any SAE, including death, resulting from any cause, which occurs to any participant 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 SAEs should be reported via email 
 or fax 
. 
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/IEC per their IRB/IEC policy. 
11.3.4.3. 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 nonserious AE, or 
whether it should be considered as part of the participant’s history. In addition, all events or other 
findings determined to be SAEs should be identified on the Endo Serious Adverse Event 
(SAE)/Reportable Event Form and the investigator should consider whether the event is related 
or not related to study intervention. All events determined to be nonserious should be reported on 
the eCRF. 

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11.4. 
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information 
See Section 6 and Section 9.4.5. 

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11.5. 
Appendix 5: Amendment 01 
The primary reasons for Amendment 01 were to add Cohort 6, include the requirement of having 
a qualified designated physician administer CCH-aaes, include precautions regarding the 
potential of an allergic reaction, and add certain inclusion/exclusion criteria. The major changes 
to the protocol are outlined below. Revisions in style, minor corrections (such as spelling errors, 
etc), and other minor changes that do not impact content may also have been made. 
Section 
Reason for Change/Original Text 
Revision 
Section 2.1 Synopsis 
Section 3.3 Benefit-
Risk Assessment 
Section 5.1 Overall 
Design 
Section 9.4 Adverse 
Events and Serious 
Adverse Events 
Section 11.3.2 
Relationship to Study 
Intervention 
Modifying the depth of injection 
will also be assessed in Cohorts 3 
and 4: 
…different doses, strengths 
(concentrations), diluent additives, 
and methods of injection… 
… different doses, strengths 
(concentrations), diluent additives, 
depths of injection, and methods of 
injection …. 
Section 2.1 Synopsis 
Added an additional cohort 
(Cohort 6). 
Added a description of Cohort 6 to the 
Study Intervention Cohort in the 
Synopsis table. 
Section 2.1 Synopsis 
Section 5.1 Overall 
Design 
Added an additional cohort 
(Cohort 6). 
Added a description of Cohort 6 in the 
overall study design. 
Participants in Cohort 6 will receive a 
maximum dose of up to 0.42 mg of 
QWO (CCH-aaes) on the control side 
and a maximum dose of up to 0.21 mg 
of QWO (CCH-aaes) on the 
investigational side per treatment 
session for 2 treatment sessions 
(Days 1 and 43) for a maximum total 
dose of 1.26 mg. 
In Cohort 6, the investigational and 
control sides will be treated with the 
same number of injections, the same 
number of aliquots per injection, and 
extended treatment interval, but at 
different doses and concentrations. 

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Section 
Reason for Change/Original Text 
Revision 
Section 2.1 Synopsis 
Section 5.1 Overall 
Design 
Clarified description of Cohorts 1 
and 5. 
In an effort to standardize the risk and 
scope of bruising, the investigational 
and control sides in Cohorts 1 and 5 
should be treated with the same 
concentration, same number of 
injections, and same number of 
aliquots per injection, but at different 
doses per injection or addition of 
diluent additive. 
Section 2.1 Synopsis 
Section 5.1 Overall 
Design 
Section 10 Sample 
Size Determination 
Number of participants updated 
because of addition of Cohort 6.  
 
… to enroll approximately 180 
participants into 6 treatment cohorts of 
up to 30 participants each, such that up 
to 144 participants complete the study. 
Section 2.3 Study 
Schema for Cohort 6 
 
New study schema added for Cohort 6. 
Section 2.4 Schedule 
of Assessments for 
Cohorts 1 to 5 
In order to establish a baseline for 
bruising there should be an IABSS 
performed prior to study drug 
injection. 
Added in the SoA that there should be 
an Investigator Assessment of Bruising 
Severity Scale (IABSS) performed at 
Day 1. 
Section 2.4 Schedule 
of Assessments for 
Cohort 1 to 5  
Section 3.3 Benefit-
Risk Assessment 
Section 7.1 Selection 
and Marking of 
Dimples 
Section 9.1.2 Physical 
Examination 
Section 9.1.3 
Fitzpatrick Skin Scale 
Section 9.3.3 Clinical 
Laboratory 
Determinations 
Certain study assessments and 
administration of QWO (CCH-aaes) 
should always be performed by the 
investigator who will be a qualified 
physician. 
Added "qualified designated 
physician" to various sections of the 
protocol. 
Section 2.7 Schedule 
of Assessments for 
Cohort 6 
 
New SoA added for Cohort 6. 
Section 3.3.3 Half-
dose QWO (CCH-
aaes) 
Added an additional cohort. 
In Cohort 6, half the labeled dose 
(0.42 mg) of QWO (CCH-aaes) will be 
administered to the control side. 

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Section 
Reason for Change/Original Text 
Revision 
Section 3.3.4 Quarter-
dose QWO (CCH-
aaes) 
Added an additional cohort. 
In Cohort 6, one-quarter of the labeled 
dose (0.21 mg) at one-half of the 
labeled concentration (0.12 mg/mL) of 
QWO (CCH-aaes) will be administered 
to the investigational side. Half of the 
labeled dose (0.42 mg) of QWO 
(CCH-aaes) at the labeled 
concentration (0.23 mg/mL) will be 
administered to the control side. 
Cohort 6 will consist of 2 treatment 
sessions, 6 weeks apart. The total dose 
administered for Cohort 6 to the 
participant in both the investigational 
and control sides during the study will 
be QWO (CCH-aaes) 1.26 mg. The 
purpose of decreasing the 
dose/concentration and lengthening the 
interval between Treatment Session 1 
(Day 1) and Treatment Session 2 
(Day 43 ± 3 days) is to determine 
whether there will be an improvement 
in both bruising and subsequent 
discoloration. 
Section 5.2 Scientific 
Rationale for Study 
Design 
Added an additional cohort. 
…half the labeled dose (0.42 mg) of 
QWO (CCH-aaes) and one-quarter of 
the labeled dose (0.21 mg) of QWO 
(CCH-aaes) at one-half the labeled 
concentration (0.12 mg/mL) (Cohort 
6). For Cohort 6, there will be 2 
treatment sessions administered 6 
weeks apart. 
Section 5.4 
Justification for Dose 
Added an additional cohort. 
For Cohort 6, half the labeled dose 
(0.42 mg for the control side) and one-
quarter of the labeled dose at one-half 
the labeled concentration (0.21 mg at a 
concentration of 0.12 mg/mL for the 
investigational side) will be 
administered as 2 treatment sessions, 6 
weeks apart. This is to determine 
whether a decrease in the dose and 
concentration combined with 
lengthening the time between treatment 
administration will decrease bruising 
and subsequent discoloration (refer to 
Section 5.2 for additional information). 
Table 1 Study 
Intervention Cohorts 
Section 2.1 Synopsis 
Added an additional cohort. 
Cohort 6 information added to Table 1 

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Section 
Reason for Change/Original Text 
Revision 
Table 2 Study 
Intervention by 
Buttock 
Added an additional cohort. 
Cohort 6 information added to Table 2 
Section 5.2 Scientific 
Rationale for Study 
Design 
Added an additional cohort. 
Study AUX-CC-831 tested QWO 
(CCH-aaes) at 0.06 mg, 0.48 mg, and 
0.84 mg. The study demonstrated 
improvement in a variety of parameters 
with the 0.06 mg dose, and 
investigators determined that 
approximately 45% of participants had 
improvement in their cellulite, 
although it was not statistically 
significant. The 0.48 mg dose was 
associated with statistically significant 
improvements. Therefore, in this study, 
Cohort 6 will evaluate a QWO (CCH-
aaes) dose between the lowest and the 
middle dose given in Study  
AUX-CC-831, to determine whether 
there will be a decrease in bruising 
while experiencing an improvement in 
cellulite. 
Section 7.2.8 Cohort 
6, Investigational 
Side Only, QWO 
(CCH-aaes) – 
Quarter-dose with 
Two Treatment 
Sessions at 
approximately 43 
Study Days in 
between Visits 
Added an additional cohort. 
Dosage and Mode of Administration: 
For the investigational side, a dose of 
up to 0.21 mg of QWO (CCH-aaes) up 
to 1.8 mL will be administered as up to 
12 subcutaneous injections (0.15-mL 
injection administered as three 
0.05-mL aliquots per injection). There 
will be 2 treatment visits at an interval 
of approximately 42 days as described 
in schedule of assessments for Cohort 
6. The volume and dose of injection at 
each treatment visit for each buttock 
will be prepared per the Pharmacy 
Manual and injected per the Injection 
Guide in the Study Operations Manual. 
Section 6.1 
Participant Inclusion 
Criteria  
Added text not allowing site staff to 
participate in the study. 
Be a non-employee or non-family 
member of the sponsor or research 
staff conducting the study. 
Section 6.2 
Participant Exclusion 
Criteria 
Added exclusion criterion to 
disallow other investigational 
product. 
15. Has received treatment with any 
investigational product within 30 days 
(or 5 half-lives, whichever is longer) of 
the start of the Screening Visit or 
throughout the study. 

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Section 
Reason for Change/Original Text 
Revision 
Section 6.3 Lifestyle 
Considerations 
Clarified who could give advice. 
Participants should avoid medications, 
homeopathic supplements, or foods as 
advised by the qualified designated 
physician or designee prior to QWO 
(CCH-aaes) treatment. 
Section 7.2.11 Care 
Procedures After 
Injection 
Added text regarding potential for 
an allergic reaction due to the 
foreign protein CCH.  
New section added: Care After 
Injection. 
NOTE: CCH is a foreign protein and 
investigators must be prepared to 
address and manage an allergic 
reaction should it occur. At the time of 
each injection, a 1:1,000 solution of 
epinephrine for injection, 50 mg 
diphenhydramine injection or a 
suitable equivalent, and oxygen must 
be available, and the investigator and 
site staff must be familiar with their 
use.  
To evaluate the participant for possible 
immediate immunological AEs, the 
participant will remain in direct 
observation of medical personnel who 
are skilled in the management of an 
allergic reaction for 30 minutes after 
receiving the injections of the study 
intervention and until the participant 
exhibits no sign of an immunological 
or other clinically significant systemic 
or local AE. The participant’s vital 
signs must be stable before the 
participant can leave direct 
observation.  
Section 6.2.9 
Continued Access to 
Study Intervention 
after the End of the 
Study 
Section deleted. Additional 
treatment with QWO (CCH-aaes) 
will not be provided after the End of 
Study. 
 
Section 9.1.4 Hexsel 
Cellulite Scale 
Severity 
Correct Hexsel CSS Total Score 
inconsistency found in Section 9.1.4 
of protocol 
Participants must have a Hexsel CSS 
total score ≤ 12 to be included in the 
study 
 

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11.6. 
Abbreviations 
Abbreviation 
Explanation 
AE 
Adverse event 
CCH 
Collagenase clostridium histolyticum 
CR-PCSS 
Clinician Reported Photonumeric Cellulite Severity Scale 
CSS 
Cellulite Severity Scale 
eCRF 
Electronic case report form 
ET 
Early termination 
HIPAA 
Health Insurance Portability and Accountability Act 
IABSS 
Investigator Assessment of Bruising Severity Scale 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
I-GAIS 
Investigator-Global Aesthetic Improvement Scale 
IRB 
Institutional Review Board 
PT 
Preferred term 
SAE 
Serious adverse event 
SOC 
System organ class 
SUSAR 
Suspected, unexpected serious adverse reactions 
TEAE 
Treatment-emergent adverse event 
TID 
Three times daily 
 

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12. 
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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13. 
REFERENCES 
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. 
Endo Pharmaceuticals Inc. A phase 4, open-label study to assess effects of mitigation treatments 
on bruising of CCH-aaes treatment of buttock cellulite in adult females [Clinical Study Report 
EN3835-401]. Malvern, PA; 21 March 2022. 
Funt D, Pavicic T. Dermal fillers in aesthetics: an overview of adverse events and treatment 
approaches. Clin Cosmet Investig Dermatol. 2013;6:295-316. Published 2013 Dec 12. 
doi:10.2147/CCID.S50546 
Green JB, Cohen JL. Cellfina observations: pearls and pitfalls. Semin Cutan Med Surg. 
2015;34(3):144-146. doi:10.12788/j.sder.2015.0176 
Hexsel DM, Dal'forno T, Hexsel CL. A validated photonumeric cellulite severity scale. J Eur 
Acad Dermatol Venereol. 2009;23(5):523-528. doi:10.1111/j.1468-3083.2009.03101.x 
Meaidi A, Mørch L, Torp-Pedersen C, Lidegaard O. Oral tranexamic acid and thrombosis risk in 
women. EClinicalMedicine. 2021;35:100882. Published 2021 May 6. 
doi:10.1016/j.eclinm.2021.100882 
Mehdizadeh M, Ghassemi A, Khakzad M, et al. Comparison of the Effect of Dexamethasone and 
Tranexamic Acid, Separately or in Combination on Post-Rhinoplasty Edema and Ecchymosis. 
Aesthetic Plast Surg. 2018;42(1):246-252. doi:10.1007/s00266-017-0969-x 
Nürnberger F, Müller G. So-called cellulite: an invented disease. J Dermatol Surg Oncol. 
1978;4(3):221-229. doi:10.1111/j.1524-4725.1978.tb00416.x 
Ockerman A, Vanassche T, Garip M, et al. Tranexamic acid for the prevention and treatment of 
bleeding in surgery, trauma and bleeding disorders: a narrative review. Thromb J. 2021;19(1):54. 
Published 2021 Aug 11. doi:10.1186/s12959-021-00303-9 
QWO. Prescribing Information. Endo Global Aesthetics Limited; July 2020. Accessed 
21 March 2022. www.qwo.com 
Rohrich RJ, Cho MJ. The Role of Tranexamic Acid in Plastic Surgery: Review and Technical 
Considerations. Plast Reconstr Surg. 2018;141(2):507-515. 
doi:10.1097/PRS.0000000000003926 
Samdal F, Amland PF, Bugge JF. Plasma lidocaine levels during suction-assisted lipectomy 
using large doses of dilute lidocaine with epinephrine. Plast Reconstr Surg. 1994;93(6):1217-
1223. doi:10.1097/00006534-199405000-00017 

EN3835-226 CEL Protocol Amendment 02 
RIM-CLIN-004697 v1.0 
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Taeuber I, Weibel S, Herrmann E, et al. Association of Intravenous Tranexamic Acid With 
Thromboembolic Events and Mortality: A Systematic Review, Meta-analysis, and Meta-
regression [published online ahead of print, 2021 Apr 14]. JAMA Surg. 2021;156(6):e210884. 
doi:10.1001/jamasurg.2021.0884 
Tranexamic Acid. Prescribing Information. Amring Pharmaceuticals; December 2020. Accessed 
02 August 2022. https://dailymed.nlm.nih.gov/dailymed 
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  
Whipple LA, Fournier CT, Heiman AJ, et al. The Anatomical Basis of Cellulite Dimple 
Formation: An Ultrasound-Based Examination. Plast Reconstr Surg. 2021;148(3):375e-381e. 
doi:10.1097/PRS.0000000000008218 
Wokes JET, Erdmann MWH, McLean NR. The Role of Tranexamic Acid in Aesthetic Plastic 
Surgery: A Survey of the British Association of Aesthetic Plastic Surgeons. Aesthet Surg J. 
2021;41(2):244-249. doi:10.1093/asj/sjaa149