Clinical trial NCT01987986: A Phase 2, Randomized, Double-blind, Placebo Controlled Dose Ranging Study of Repeat Doses of AA4500 for the Treatment of Edematous Fibrosclerotic Panniculopathy
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Edematous Fibrosclerotic Panniculopathy (EFP)
Keywords: cellulite
dimple
orange peel
cottage cheese
mattress texture
Lead sponsor: Endo Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2013-11-20
Enrollment: 150
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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
20. Has a tattoo located within 2 cm of the site of injection
21. Is presently nursing a baby or providing breast milk for a baby.
22. Intends to become pregnant during the study.
23. Intends to initiate an intensive sport or exercise program during the study.
24. Has received an investigational drug or treatment within 30 days before injection of AA4500.
25. Has a known systemic allergy to collagenase or any other excipient of AA4500.
26. Has received any collagenase treatments within 30 days before treatment.

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Primary outcomes:
measure: Investigator Global Assessment of Aesthetic Improvement
timeFrame: Baseline, Day 73
Secondary outcomes:
Other outcomes:
measure: Investigator Cellulite Severity Score (CSS) Total Score- Change From Baseline
timeFrame: Baseline, Day 73
measure: Subject Cellulite Severity Item (CSI)-Change From Baseline
timeFrame: Baseline, Day 73
measure: Subject Global Bother Assessment (SGBA)- Change From Baseline
timeFrame: Baseline, Day 73
measure: Subject-reported Cellulite Impact Scale (SR-CIS)-Change From Baseline
timeFrame: Baseline, Day 73
measure: Subject Satisfaction With Treatment Assessment (SCTA)
timeFrame: Day 73
measure: Subject Global Assessment Cellulite (SGA-C)
timeFrame: Day 73
measure: Subject Global Assessment of Aesthetic Improvement (C-GAIS)
timeFrame: Day 73
Locations:
city: San Diego
country: United States
facility: Dermatology Cosmetic Laser Medical Associates of La Jolla
state: California
city: Santa Monica
country: United States
facility: ATS Clinical Research
state: California
city: Coral Gables
country: United States
facility: Dermatology Research Institute
state: Florida
city: West Palm Beach
country: United States
facility: Kenneth Beer, MD PA
state: Florida
city: Washington
country: United States
facility: Mercy Health Research
state: Missouri
city: New York
country: United States
facility: Sadick Research Group
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Nashville
country: United States
facility: Tennessee Clinical Research Center
state: Tennessee
city: Charlottesville
country: United States
facility: Charlottesville Dermatology
state: Virginia
city: Spokane
country: United States
facility: Premier Clinical Research
state: Washington
Study officials:
affiliation: Endo Pharmaceuticals
name: Veronica Urdaneta, MD MPH
role: STUDY_DIRECTOR
References: