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

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ClinicalTrials.gov Identifier: NCT01987986
Recruitment Status : Completed
First Posted : November 20, 2013
Results First Posted : July 2, 2017
Last Update Posted : October 5, 2017
Sponsor:
Information provided by (Responsible Party):
Endo Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE October 30, 2013
First Posted Date  ICMJE November 20, 2013
Results First Submitted Date  ICMJE April 18, 2017
Results First Posted Date  ICMJE July 2, 2017
Last Update Posted Date October 5, 2017
Study Start Date  ICMJE October 2013
Actual Primary Completion Date August 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 31, 2017)
Investigator Global Assessment of Aesthetic Improvement [ Time Frame: 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).
Original Primary Outcome Measures  ICMJE
 (submitted: November 13, 2013)
Investigator assessed aesthetic change/improvement in treatment quadrant [ Time Frame: Day 73 ]
Change History Complete list of historical versions of study NCT01987986 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: May 31, 2017)
  • Investigator Cellulite Severity Score (CSS) Total Score- Change From Baseline [ Time Frame: 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.
  • Subject Cellulite Severity Item (CSI)-Change From Baseline [ Time Frame: 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.
  • Subject Global Bother Assessment (SGBA)- Change From Baseline [ Time Frame: 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.
  • Subject-reported Cellulite Impact Scale (SR-CIS)-Change From Baseline [ Time Frame: 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.
  • Subject Satisfaction With Treatment Assessment (SCTA) [ Time Frame: 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)
  • Subject Global Assessment Cellulite (SGA-C) [ Time Frame: 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
  • Subject Global Assessment of Aesthetic Improvement (C-GAIS) [ Time Frame: 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).
Original Other Pre-specified Outcome Measures
 (submitted: November 13, 2013)
  • Cellulite severity scale score change/improvement in treatment quadrant [ Time Frame: Day 73 ]
    All noted endpoints will be evaluated at Day 73
  • Subject assessed treatment change/improvement in treatment quadrant [ Time Frame: Day 73 ]
    All noted endpointed will be evaluated at Day 73
  • Photo numeric variable change. [ Time Frame: Day 73 ]
    All noted endpoints will be evaluated at Day 73
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE A Phase 2, Double-blind and Placebo Dose Ranging Study of Repeat Doses of AA4500 for the Treatment of Edematous Fibrosclerotic Panniculopathy
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Edematous Fibrosclerotic Panniculopathy (EFP)
Intervention  ICMJE
  • Biological: Collagenase Clostridium Histolyticum
    injectible intervention
    Other Names:
    • AA4500
    • Xiaflex
    • Xiapex
  • Biological: Placebo
Study Arms  ICMJE
  • 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.

    Intervention: Biological: Collagenase Clostridium Histolyticum
  • 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.

    Intervention: Biological: Collagenase Clostridium Histolyticum
  • 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.

    Intervention: Biological: Collagenase Clostridium Histolyticum
  • Placebo Comparator: Placebo

    Placebo

    Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days.

    Intervention: Biological: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 27, 2014)
150
Original Estimated Enrollment  ICMJE
 (submitted: November 13, 2013)
144
Actual Study Completion Date  ICMJE August 2014
Actual Primary Completion Date August 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

    -

Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01987986
Other Study ID Numbers  ICMJE AUX-CC-831
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Endo Pharmaceuticals
Study Sponsor  ICMJE Endo Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Veronica Urdaneta, MD MPH Endo Pharmaceuticals
PRS Account Endo Pharmaceuticals
Verification Date September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP