A Phase 2, Randomized, Double-blind, Placebo Controlled Dose Ranging Study of Repeat Doses of AA4500 for the Treatment of Edematous Fibrosclerotic Panniculopathy

• Sponsor: Endo Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01987986
• Collaborator: (none)
• Enrollment: 150
• Locations: 10
• Arms: 4
• Duration (Months): 10
• Patients Per Site: 15
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

To assess the safety and effectiveness of repeat doses of AA4500 in the treatment of edematous fibrosclerotic panniculopathy (EFP) commonly known as cellulite in adult women.

Condition or Disease	Intervention/Treatment	Phase
Edematous Fibrosclerotic Panniculopathy (EFP)	Biological: Collagenase Clostridium Histolyticum; Biological: Placebo	Phase 2

Detailed Description

The Phase 2a study is a randomized, double-blind multiple-dose study that is expected to enroll approximately 144 women between the ages of 18 and 45 in the United States. Treatment effectiveness will be evaluated by investigator and patient assessments, as well as 3-D photographic imaging techniques. Once the safety and local tolerability profile from the first stage has been found to be acceptable subjects will be enrolled in stage 2. After an interim safety and local tolerability review was completed of all subjects in stage 1, it was determined that enrollment in stage 2 is acceptable and has been initiated.

Study Design

• Study Type: Interventional
• Actual Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Double-blind and Placebo Dose Ranging Study of Repeat Doses of AA4500 for the Treatment of Edematous Fibrosclerotic Panniculopathy
• Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: Aug 1, 2014
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AA4500 0.06 mg (low dose) AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days.	Biological: Collagenase Clostridium Histolyticum; injectible intervention; Other Names: AA4500 Xiaflex Xiapex
Experimental: AA4500 0.48 mg (mid-dose) AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days.	Biological: Collagenase Clostridium Histolyticum; injectible intervention; Other Names: AA4500 Xiaflex Xiapex
Experimental: AA4500 0.84 mg (high dose) AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days.	Biological: Collagenase Clostridium Histolyticum; injectible intervention; Other Names: AA4500 Xiaflex Xiapex
Placebo Comparator: Placebo Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days.	Biological: Placebo

Outcome Measures

Primary Outcome Measures

1. Investigator Global Assessment of Aesthetic Improvement [Baseline, Day 73]

   Investigators assessment of aesthetic improvement (I-GAIS) scores ranged from 3 to -1 as follows: 3 (very much improved), 2 (much improved), 1 (improved), 0 (no change), -1 (worse).

Other Outcome Measures

1. Investigator Cellulite Severity Score (CSS) Total Score- Change From Baseline [Baseline, Day 73]

   The CSS is a photonumeric scale that was used to evaluate 5 morphologic features of cellulite; (A) number of evident depressions, (B) depth of depressions, (C) morphological appearance of skin surface alterations, (D) laxity, flaccidity or sagging of skin, and (E) current classification scale based on medical literature including Nuernberger and Mueller. The severity of each feature is rated on a scale from 0 (none) to 3 (most severe). The CSS total score is the sum of the 5 cellulite features (range: 0 to 15, with higher scores corresponding to more severe cellulite). Change is Day 73 study visit rating minus baseline rating; negative values indicate improvement in cellulite.

2. Subject Cellulite Severity Item (CSI)-Change From Baseline [Baseline, Day 73]

   CSI scores ranged from 0 (no cellulite present), 1 (very mild), 2 (mild), 3 (moderate), 4 (severe) to 5 (very severe). Change is Day 73 study visit rating minus baseline rating; negative values indicate a lessening in cellulite severity.

3. Subject Global Bother Assessment (SGBA)- Change From Baseline [Baseline, Day 73]

   Subjects rated their cellulite on a scale from 0 (not at all bothered) to 4 (extremely bothered). Change from baseline is Day 73 study visit value minus baseline value; negative change reflects an improvement in the amount the subject was bothered by cellulite; positive change reflects a worsening in the amount the subject is bothered by cellulite.

4. Subject-reported Cellulite Impact Scale (SR-CIS)-Change From Baseline [Baseline, Day 73]

   Subjects were asked to answer 6 exploratory questions regarding the appearance of their cellulite on a scale of 0 to 10 with 0 representing "not at all" and 10 representing "extremely." A SR-CIS total score was derived from these 6 questions with values varying from 0 (No negative impact) to 60 (Extreme negative impact). Change from baseline is Day 73 value minus baseline value; negative change reflects an improvement.

5. Subject Satisfaction With Treatment Assessment (SCTA) [Day 73]

   Subjects rated their treatment satisfaction at the Day 73 visit on a 5-point scale ranging from -2 (very dissatisfied) to +2 (very satisfied)

6. Subject Global Assessment Cellulite (SGA-C) [Day 73]

   Subjects assessed their cellulite based on a 5-point scale from -1 (slightly worse), 0 (same), 1 (slightly improved), 2 (moderately improved), to 3 (much improved) on Day 73

7. Subject Global Assessment of Aesthetic Improvement (C-GAIS) [Day 73]

   Subjects's assessment of aesthetic improvement (C-GAIS) scores ranged from 3 to -1 as follows: 3 (very much improved), 2 (much improved), 1 (improved), 0 (no change), -1 (worse).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Be a female between 18 to 45 years of age.

2. Have at least one well defined dimple that is at least 1 cm but not more than 2 cm along the long axis and that is evident when the subject is standing

3. Have a photonumeric cellulite severity scale (CSS) score between 6 and 12

4. Have a Body Mass Index (BMI) >19 and <30 kg/m2, and intends to maintain stable body weight throughout the duration of the study

5. Be willing to apply appropriate sunscreen to the selected quadrant before each exposure to the sun while participating in the study

6. Be judged to be in good health, based upon the results of a medical history, physical examination, and laboratory profile at screening.

7. Have a negative urine pregnancy test at screening and before injection of AA4500 and be using an effective contraception method (ie, abstinence, intrauterine device [IUD], hormonal [estrogen/progestin] contraceptives, or barrier control) for at least one menstrual cycle prior to study enrollment and for the duration of the study.

8. Be willing and able to cooperate with the requirements of the study.

9. Voluntarily sign and date an informed consent agreement approved by the Institutional Review Board/Independent Ethics Committee/Human Research Ethics Committee (IRB/IEC/HREC).

10. Be able to read, complete and understand the Patient Reported Outcomes rating instruments in English.

Exclusion Criteria:

1. Thyroid disease, unless controlled with medication for ≥ 6 months

2. Uncontrolled diabetes mellitus, as determined by the investigator

3. Uncontrolled hypertension, as determined by the investigator

4. Vascular disorder (eg, phlebitis or varicose veins) in area to be treated

5. Lipedema or a lymphatic disorder

6. Cushing's disease and/or use of systemic corticosteroids

7. History of lower extremity thrombosis or post-thrombosis syndrome

8. Documented autoimmune disorder such as lupus erythematosus, rheumatoid arthritis

9. Inflammation or active infection in area to be treated

10. Cutaneous alteration in area to be treated

11. Rash, eczema, psoriasis, or skin cancer in the area to be treated

12. History of keloidal scarring or abnormal wound healing

13. Coagulation disorder

14. Taking a medication for chronic anticoagulation (except for ≤ 150 mg aspirin daily)

15. Known active hepatitis A, B or C

16. Known immune deficiency disease or a positive test for human immunodeficiency virus (HIV)

17. Other significant conditions including body dysmorphic disorder, which in the investigator's opinion would make the subject unsuitable for enrollment in the study

18. Is menopausal defined as 12 months of amenorrhea in the absence of other biological or physiological causes, as determined by the investigator

19. Has used any of the following for the treatment of EFP on the legs or buttock within the timelines identified below or intends to use any of the following at any time during the course of the study:

• Liposuction on the side of the body selected for treatment during the 12-month period before injection of AA4500

• Injections (eg, mesotherapy); radiofrequency device treatments; laser treatment; or surgery (including subcision) within the selected treatment quadrant during the 12-month period before injection of AA4500

• Endermologie or similar treatments within the selected treatment quadrant during the 6-months period before injection of AA4500

• Massage therapy within the selected treatment quadrant during the 3-month period before injection of AA4500

• Creams (eg, Celluvera™, TriLastin®) to prevent or mitigate EFP within the selected treatment quadrant during the 2-week period before injection of AA4500

1. Has a tattoo located within 2 cm of the site of injection

2. Is presently nursing a baby or providing breast milk for a baby.

3. Intends to become pregnant during the study.

4. Intends to initiate an intensive sport or exercise program during the study.

5. Has received an investigational drug or treatment within 30 days before injection of AA4500.

6. Has a known systemic allergy to collagenase or any other excipient of AA4500.

7. Has received any collagenase treatments within 30 days before treatment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dermatology Cosmetic Laser Medical Associates of La Jolla	San Diego	California	United States	92121
2	ATS Clinical Research	Santa Monica	California	United States	90404
3	Dermatology Research Institute	Coral Gables	Florida	United States	33146
4	Kenneth Beer, MD PA	West Palm Beach	Florida	United States	33401
5	Mercy Health Research	Washington	Missouri	United States	63090
6	Sadick Research Group	New York	New York	United States	10075
7	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
8	Tennessee Clinical Research Center	Nashville	Tennessee	United States	37215
9	Charlottesville Dermatology	Charlottesville	Virginia	United States	22911
10	Premier Clinical Research	Spokane	Washington	United States	99204

Sponsors and Collaborators

• Endo Pharmaceuticals

Investigators

• Study Director: Veronica Urdaneta, MD MPH, Endo Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Endo Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01987986
• Other Study ID Numbers: AUX-CC-831
• First Posted: Nov 20, 2013
• Last Update Posted: Oct 5, 2017
• Last Verified: Sep 1, 2017

• Keywords provided by Endo Pharmaceuticals: cellulite; dimple; orange peel; cottage cheese; mattress texture
• Additional relevant MeSH terms: Edema

Study Results

Participant Flow

Arm/Group Title	AA4500 0.06 mg (Low Dose)	AA4500 0.48 mg (Mid-dose)	AA4500 0.84 mg (High Dose)	Placebo
Arm/Group Description	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Placebo
Period Title: Overall Study
STARTED	43	43	40	24
COMPLETED	41	43	38	24
NOT COMPLETED	2	0	2	0

Baseline Characteristics

Arm/Group Title	AA4500 0.06 mg (Low Dose)	AA4500 0.48 mg (Mid-dose)	AA4500 0.84 mg (High Dose)	Placebo	Total
Arm/Group Description	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Placebo	Total of all reporting groups
Overall Participants	43	43	40	24	150
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.7 (5.78)	36.8 (7.07)	36.1 (5.62)	37.3 (8.08)	36.9 (6.50)
Age, Customized (Count of Participants)
<25	2 4.7%	3 7%	2 5%	1 4.2%	8 5.3%
25-34	6 14%	11 25.6%	12 30%	6 25%	35 23.3%
35-44	33 76.7%	23 53.5%	25 62.5%	13 54.2%	94 62.7%
>=45	2 4.7%	6 14%	1 2.5%	4 16.7%	13 8.7%
Sex: Female, Male (Count of Participants)
Female	43 100%	43 100%	40 100%	24 100%	150 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	10 23.3%	13 30.2%	9 22.5%	4 16.7%	36 24%
Not Hispanic or Latino	33 76.7%	30 69.8%	31 77.5%	20 83.3%	114 76%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Asian	0 0%	0 0%	0 0%	1 4.2%	1 0.7%
Black or African American	2 4.7%	3 7%	4 10%	2 8.3%	11 7.3%
White	40 93%	40 93%	36 90%	20 83.3%	136 90.7%
Other	1 2.3%	0 0%	0 0%	1 4.2%	2 1.3%
Region of Enrollment (participants) [Number]
United States	43 100%	43 100%	40 100%	24 100%	150 100%

Outcome Measures

1. Primary Outcome

Title	Investigator Global Assessment of Aesthetic Improvement
Description	Investigators assessment of aesthetic improvement (I-GAIS) scores ranged from 3 to -1 as follows: 3 (very much improved), 2 (much improved), 1 (improved), 0 (no change), -1 (worse).
Time Frame	Baseline, Day 73

Outcome Measure Data

Analysis Population Description

All subjects who received at least one injection of study drug and had at least one post-injection efficacy measurement.

Arm/Group Title	AA4500 0.06 mg (Low Dose)	AA4500 0.48 mg (Mid-dose)	AA4500 0.84 mg (High Dose)	Placebo
Arm/Group Description	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Placebo
Measure Participants	43	43	40	24
Mean (Standard Deviation) [units on a scale]	0.7 (0.82)	0.9 (0.93)	1.1 (0.91)	0.5 (0.72)

2. Other Pre-specified Outcome

Title	Investigator Cellulite Severity Score (CSS) Total Score- Change From Baseline
Description	The CSS is a photonumeric scale that was used to evaluate 5 morphologic features of cellulite; (A) number of evident depressions, (B) depth of depressions, (C) morphological appearance of skin surface alterations, (D) laxity, flaccidity or sagging of skin, and (E) current classification scale based on medical literature including Nuernberger and Mueller. The severity of each feature is rated on a scale from 0 (none) to 3 (most severe). The CSS total score is the sum of the 5 cellulite features (range: 0 to 15, with higher scores corresponding to more severe cellulite). Change is Day 73 study visit rating minus baseline rating; negative values indicate improvement in cellulite.
Time Frame	Baseline, Day 73

Outcome Measure Data

Analysis Population Description

All subjects who received at least one injection of study drug and had at least one post-injection efficacy measurement.

Arm/Group Title	AA4500 0.06 mg (Low Dose)	AA4500 0.48 mg (Mid-dose)	AA4500 0.84 mg (High Dose)	Placebo
Arm/Group Description	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Placebo
Measure Participants	43	43	40	24
Mean (Standard Deviation) [units on a scale]	-1.1 (1.74)	-1.3 (1.70)	-1.9 (2.37)	-0.7 (1.52)

3. Other Pre-specified Outcome

Title	Subject Cellulite Severity Item (CSI)-Change From Baseline
Description	CSI scores ranged from 0 (no cellulite present), 1 (very mild), 2 (mild), 3 (moderate), 4 (severe) to 5 (very severe). Change is Day 73 study visit rating minus baseline rating; negative values indicate a lessening in cellulite severity.
Time Frame	Baseline, Day 73

Outcome Measure Data

Analysis Population Description

All subjects who received at least one injection of study drug and had at least one post-injection efficacy measurement.

Arm/Group Title	AA4500 0.06 mg (Low Dose)	AA4500 0.48 mg (Mid-dose)	AA4500 0.84 mg (High Dose)	Placebo
Arm/Group Description	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Placebo
Measure Participants	43	43	40	24
Mean (Standard Deviation) [units on a scale]	-0.7 (1.22)	-1.1 (1.07)	-1.3 (1.34)	-0.8 (1.35)

4. Other Pre-specified Outcome

Title	Subject Global Bother Assessment (SGBA)- Change From Baseline
Description	Subjects rated their cellulite on a scale from 0 (not at all bothered) to 4 (extremely bothered). Change from baseline is Day 73 study visit value minus baseline value; negative change reflects an improvement in the amount the subject was bothered by cellulite; positive change reflects a worsening in the amount the subject is bothered by cellulite.
Time Frame	Baseline, Day 73

Outcome Measure Data

Analysis Population Description

All subjects who received at least one injection of study drug and had at least one post-injection efficacy measurement.

Arm/Group Title	AA4500 0.06 mg (Low Dose)	AA4500 0.48 mg (Mid-dose)	AA4500 0.84 mg (High Dose)	Placebo
Arm/Group Description	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Placebo
Measure Participants	43	43	40	24
Mean (Standard Deviation) [units on a scale]	-0.9 (1.33)	-1.0 (1.23)	-1.0 (1.12)	-1.0 (1.33)

5. Other Pre-specified Outcome

Title	Subject-reported Cellulite Impact Scale (SR-CIS)-Change From Baseline
Description	Subjects were asked to answer 6 exploratory questions regarding the appearance of their cellulite on a scale of 0 to 10 with 0 representing "not at all" and 10 representing "extremely." A SR-CIS total score was derived from these 6 questions with values varying from 0 (No negative impact) to 60 (Extreme negative impact). Change from baseline is Day 73 value minus baseline value; negative change reflects an improvement.
Time Frame	Baseline, Day 73

Outcome Measure Data

Analysis Population Description

All subjects who received at least one injection and who had at least one post-injection efficacy measurement.

Arm/Group Title	AA4500 0.06 mg (Low Dose)	AA4500 0.48 mg (Mid-dose)	AA4500 0.84 mg (High Dose)	Placebo
Arm/Group Description	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Placebo
Measure Participants	43	43	40	24
Mean (Standard Deviation) [units on a scale]	-15.0 (18.9)	-18.0 (15.70)	-17.7 (14.61)	-11.9 (13.97)

6. Other Pre-specified Outcome

Title	Subject Satisfaction With Treatment Assessment (SCTA)
Description	Subjects rated their treatment satisfaction at the Day 73 visit on a 5-point scale ranging from -2 (very dissatisfied) to +2 (very satisfied)
Time Frame	Day 73

Outcome Measure Data

Analysis Population Description

All subjects who received at least one injection of study drug and had at least one post -injection efficacy measurement.

Arm/Group Title	AA4500 0.06 mg (Low Dose)	AA4500 0.48 mg (Mid-dose)	AA4500 0.84 mg (High Dose)	Placebo
Arm/Group Description	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Placebo
Measure Participants	43	43	40	24
Mean (Standard Deviation) [units on a scale]	0.0 (1.31)	0.9 (0.89)	0.7 (0.93)	0.1 (1.33)

7. Other Pre-specified Outcome

Title	Subject Global Assessment Cellulite (SGA-C)
Description	Subjects assessed their cellulite based on a 5-point scale from -1 (slightly worse), 0 (same), 1 (slightly improved), 2 (moderately improved), to 3 (much improved) on Day 73
Time Frame	Day 73

Outcome Measure Data

Analysis Population Description

All subjects who at least one injection of study drug and had at least one post-injection efficacy measurement.

Arm/Group Title	AA4500 0.06 mg (Low Dose)	AA4500 0.48 mg (Mid-dose)	AA4500 0.84 mg (High Dose)	Placebo
Arm/Group Description	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Placebo
Measure Participants	43	43	40	24
Mean (Standard Deviation) [units on a scale]	0.9 (1.23)	1.6 (0.85)	1.5 (1.04)	0.8 (0.96)

8. Other Pre-specified Outcome

Title	Subject Global Assessment of Aesthetic Improvement (C-GAIS)
Description	Subjects's assessment of aesthetic improvement (C-GAIS) scores ranged from 3 to -1 as follows: 3 (very much improved), 2 (much improved), 1 (improved), 0 (no change), -1 (worse).
Time Frame	Day 73

Outcome Measure Data

Analysis Population Description

All subjects who received at least one injection of study medication and had at least one post injection efficacy measurement.

Arm/Group Title	AA4500 0.06 mg (Low Dose)	AA4500 0.48 mg (Mid-dose)	AA4500 0.84 mg (High Dose)	Placebo
Arm/Group Description	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention	Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Placebo
Measure Participants	43	43	40	24
Mean (Standard Deviation) [units on a scale]	0.9 (1.14)	1.6 (0.88)	1.4 (1.03)	0.7 (0.91)

Adverse Events

Arm/Group Title	AA4500 0.06 mg (Low Dose)		AA4500 0.48 mg (Mid-dose)		AA4500 0.84 mg (High Dose)		Placebo
Arm/Group Description	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention		AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention		AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Collagenase Clostridium Histolyticum: injectible intervention		Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Placebo
All Cause Mortality
	AA4500 0.06 mg (Low Dose)		AA4500 0.48 mg (Mid-dose)		AA4500 0.84 mg (High Dose)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/43 (0%)		0/43 (0%)		0/40 (0%)		0/24 (0%)
Serious Adverse Events
	AA4500 0.06 mg (Low Dose)		AA4500 0.48 mg (Mid-dose)		AA4500 0.84 mg (High Dose)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/43 (2.3%)		0/43 (0%)		0/40 (0%)		0/24 (0%)
Infections and infestations
Pharyngeal absess	1/43 (2.3%)		0/43 (0%)		0/40 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	AA4500 0.06 mg (Low Dose)		AA4500 0.48 mg (Mid-dose)		AA4500 0.84 mg (High Dose)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/43 (65.1%)		31/43 (72.1%)		31/40 (77.5%)		7/24 (29.2%)
General disorders
Injection site brusing	27/43 (62.8%)	51	30/43 (69.8%)	60	28/40 (70%)	58	6/24 (25%)	7
Injection site pain	11/43 (25.6%)	15	18/43 (41.9%)	38	21/40 (52.5%)	41	2/24 (8.3%)	4
Injection site pruritus	0/43 (0%)	0	5/43 (11.6%)	8	7/40 (17.5%)	10	0/24 (0%)	0
Injection site swelling	3/43 (7%)	3	7/43 (16.3%)	14	5/40 (12.5%)	8	0/24 (0%)	0
Injection site discoloration	0/43 (0%)	0	5/43 (11.6%)	6	6/40 (15%)	6	0/24 (0%)	0
Injection site induration	0/43 (0%)	0	0/43 (0%)	0	3/40 (7.5%)	3	0/24 (0%)	0
Injection site discomfort	0/43 (0%)	0	0/43 (0%)	0	2/40 (5%)	3	0/24 (0%)	0
Injection site haemorrhage	0/43 (0%)	0	0/43 (0%)	0	2/40 (5%)	3	0/24 (0%)	0
Injection site nodule	0/43 (0%)	0	0/43 (0%)	0	2/40 (5%)	2	0/24 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.