Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AA4500 0.06 mg (low dose) | Experimental | AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. |
|
| AA4500 0.48 mg (mid-dose) | Experimental | AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. |
|
| AA4500 0.84 mg (high dose) | Experimental | AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. |
|
| Placebo | Placebo Comparator | Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Collagenase Clostridium Histolyticum | Biological | injectible intervention |
|
| Measure | Description | Time Frame |
|---|---|---|
| Investigator Global Assessment of Aesthetic Improvement | 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). | Baseline, Day 73 |
Not provided
| Measure | Description | Time Frame |
|---|---|---|
| Investigator Cellulite Severity Score (CSS) Total Score- Change From Baseline | 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. |
Inclusion Criteria:
Exclusion Criteria:
Thyroid disease, unless controlled with medication for ≥ 6 months
Uncontrolled diabetes mellitus, as determined by the investigator
Uncontrolled hypertension, as determined by the investigator
Vascular disorder (eg, phlebitis or varicose veins) in area to be treated
Lipedema or a lymphatic disorder
Cushing's disease and/or use of systemic corticosteroids
History of lower extremity thrombosis or post-thrombosis syndrome
Documented autoimmune disorder such as lupus erythematosus, rheumatoid arthritis
Inflammation or active infection in area to be treated
Cutaneous alteration in area to be treated
Rash, eczema, psoriasis, or skin cancer in the area to be treated
History of keloidal scarring or abnormal wound healing
Coagulation disorder
Taking a medication for chronic anticoagulation (except for ≤ 150 mg aspirin daily)
Known active hepatitis A, B or C
Known immune deficiency disease or a positive test for human immunodeficiency virus (HIV)
Other significant conditions including body dysmorphic disorder, which in the investigator's opinion would make the subject unsuitable for enrollment in the study
Is menopausal defined as 12 months of amenorrhea in the absence of other biological or physiological causes, as determined by the investigator
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:
Has a tattoo located within 2 cm of the site of injection
Is presently nursing a baby or providing breast milk for a baby.
Intends to become pregnant during the study.
Intends to initiate an intensive sport or exercise program during the study.
Has received an investigational drug or treatment within 30 days before injection of AA4500.
Has a known systemic allergy to collagenase or any other excipient of AA4500.
Has received any collagenase treatments within 30 days before treatment.
-
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Veronica Urdaneta, MD MPH | Endo USA Inc., a Keenova Therapeutics Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dermatology Cosmetic Laser Medical Associates of La Jolla | San Diego | California | 92121 | United States | ||
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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. Collagenase Clostridium Histolyticum: injectible intervention |
| FG001 | AA4500 0.48 mg (Mid-dose) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Placebo | Biological |
|
| Baseline, Day 73 |
| Subject Cellulite Severity Item (CSI)-Change From Baseline | 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. | Baseline, Day 73 |
| Subject Global Bother Assessment (SGBA)- Change From Baseline | 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. | Baseline, Day 73 |
| Subject-reported Cellulite Impact Scale (SR-CIS)-Change From Baseline | 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. | Baseline, Day 73 |
| Subject Satisfaction With Treatment Assessment (SCTA) | Subjects rated their treatment satisfaction at the Day 73 visit on a 5-point scale ranging from -2 (very dissatisfied) to +2 (very satisfied) | Day 73 |
| Subject Global Assessment Cellulite (SGA-C) | 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 | Day 73 |
| Subject Global Assessment of Aesthetic Improvement (C-GAIS) | 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). | Day 73 |
| ATS Clinical Research |
| Santa Monica |
| California |
| 90404 |
| United States |
| Dermatology Research Institute | Coral Gables | Florida | 33146 | United States |
| Kenneth Beer, MD PA | West Palm Beach | Florida | 33401 | United States |
| Mercy Health Research | Washington | Missouri | 63090 | United States |
| Sadick Research Group | New York | New York | 10075 | United States |
| Stony Brook University Medical Center | Stony Brook | New York | 11794 | United States |
| Tennessee Clinical Research Center | Nashville | Tennessee | 37215 | United States |
| Charlottesville Dermatology | Charlottesville | Virginia | 22911 | United States |
| Premier Clinical Research | Spokane | Washington | 99204 | United States |
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 |
| FG002 | 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. Collagenase Clostridium Histolyticum: injectible intervention |
| FG003 | Placebo | Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Placebo |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. Collagenase Clostridium Histolyticum: injectible intervention |
| BG001 | 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. Collagenase Clostridium Histolyticum: injectible intervention |
| BG002 | 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. Collagenase Clostridium Histolyticum: injectible intervention |
| BG003 | Placebo | Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Placebo |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Age, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Investigator Global Assessment of Aesthetic Improvement | 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). | All subjects who received at least one injection of study drug and had at least one post-injection efficacy measurement. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Day 73 |
|
|
| ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Investigator Cellulite Severity Score (CSS) Total Score- Change From Baseline | 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. | All subjects who received at least one injection of study drug and had at least one post-injection efficacy measurement. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Day 73 |
| ||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Subject Cellulite Severity Item (CSI)-Change From Baseline | 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. | All subjects who received at least one injection of study drug and had at least one post-injection efficacy measurement. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Day 73 |
| ||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Subject Global Bother Assessment (SGBA)- Change From Baseline | 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. | All subjects who received at least one injection of study drug and had at least one post-injection efficacy measurement. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Day 73 |
| ||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Subject-reported Cellulite Impact Scale (SR-CIS)-Change From Baseline | 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. | All subjects who received at least one injection and who had at least one post-injection efficacy measurement. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Day 73 |
| ||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Subject Satisfaction With Treatment Assessment (SCTA) | Subjects rated their treatment satisfaction at the Day 73 visit on a 5-point scale ranging from -2 (very dissatisfied) to +2 (very satisfied) | All subjects who received at least one injection of study drug and had at least one post -injection efficacy measurement. | Posted | Mean | Standard Deviation | units on a scale | Day 73 |
| ||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Subject Global Assessment Cellulite (SGA-C) | 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 | All subjects who at least one injection of study drug and had at least one post-injection efficacy measurement. | Posted | Mean | Standard Deviation | units on a scale | Day 73 |
| ||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Subject Global Assessment of Aesthetic Improvement (C-GAIS) | 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). | All subjects who received at least one injection of study medication and had at least one post injection efficacy measurement. | Posted | Mean | Standard Deviation | units on a scale | Day 73 |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. Collagenase Clostridium Histolyticum: injectible intervention | 0 | 43 | 1 | 43 | 28 | 43 |
| EG001 | 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. Collagenase Clostridium Histolyticum: injectible intervention | 0 | 43 | 0 | 43 | 31 | 43 |
| EG002 | 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. Collagenase Clostridium Histolyticum: injectible intervention | 0 | 40 | 0 | 40 | 31 | 40 |
| EG003 | Placebo | Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Placebo | 0 | 24 | 0 | 24 | 7 | 24 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pharyngeal absess | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injection site brusing | General disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Injection site pain | General disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Injection site pruritus | General disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Injection site swelling | General disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Injection site discoloration | General disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Injection site induration | General disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Injection site discomfort | General disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Injection site haemorrhage | General disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Injection site nodule | General disorders | MedDRA (16.1) | Systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Coordinator | Endo Pharmaceuticals Inc. | clinicalsite.inquires@endo.com |
| ID | Term |
|---|---|
| D000071697 | Cellulite |
| ID | Term |
|---|---|
| D012877 | Skin Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D003012 | Microbial Collagenase |
| C570746 | xiapex |
| ID | Term |
|---|---|
| D017364 | Collagenases |
| D008666 | Metalloendopeptidases |
| D010450 | Endopeptidases |
| D010447 | Peptide Hydrolases |
| D006867 | Hydrolases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D045726 | Metalloproteases |
Not provided
Not provided
| 25-34 |
|
| 35-44 |
|
| >=45 |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Black or African American |
|
| White |
|
| Other |
|
| OG002 | 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. Collagenase Clostridium Histolyticum: injectible intervention |
| OG003 | Placebo | Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Placebo |
|
|
| OG003 | Placebo | Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Placebo |
|
|
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
| OG003 | Placebo | Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Placebo |
|
|
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 |
| OG003 | Placebo | Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Placebo |
|
|
| OG003 | Placebo | Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Placebo |
|
|
| OG003 | Placebo | Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Placebo |
|
|
| OG003 | Placebo | Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. Placebo |
|
|