Clinical Trial: Study of AA4500 in the Treatment of Peyronie's Disease

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of the Safety and Effectiveness of AA4500 Administered Twice Per Treatment Cycle for Up to Four Treatment Cycles (2 x 4) in Men With

Brief Summary:

This study is a Phase 3, double-blind, randomized, placebo-controlled study of the safety and efficacy of AA4500 0.58 mg in subjects with Peyronie's disease. Approximately 300 (200 AA4500 and 100 placebo) men will be randomized. Subjects will be screened for study eligibility within 21 days before the initial injection of study drug in the first treatment cycle.

Before dosing, subjects will be stratified by degree of penile curvature (ie, 30º to 60º or 61º to 90º) and then randomized into two treatment groups to receive in a 2:1 ratio either AA4500 0.58 mg or placebo.

In this study, qualified subjects may receive up to four treatment cycles; each cycle will be separated by a period of 42 days (± 5 days). During each treatment cycle, subjects will receive two injections of study drug with at least 24 hours but not more than 72 hours between injections. After the final injection of each treatment cycle, the investigator or qualified designee will model the penile plaque in an attempt to stretch or elongate the plaque. If the subject's penile curvature is reduced to < 15 degrees after the first, second, or third cycle of injections or if the investigator determines further treatment is not clinically indicated (eg, adverse events; allergic reaction), subsequent treatment cycles will not be administered.

Following the maximum of four treatment cycles, each subject will be followed for additional safety and efficacy assessments on Days 169 (± 7 days), 232 (± 7 days), 295 (± 7 days), 365 (± 7 days) (nominal weeks 24, 33, 42 and 52). Subjects randomized to placebo may receive open-label AA4500 treatment after completing this study as part of another protocol.


Detailed Summary:
Sponsor: Endo Pharmaceuticals

Current Primary Outcome:

  • Percentage Change From Baseline in Penile Curvature [ Time Frame: Baseline and Week 52 ]
    A negative value in the percentage change from baseline in penile curvature deformity (angle measured in degrees) indicates less curvature.
  • Change From Baseline in the Peyronie's Disease Bother Domain of the Peyronie's Disease Questionnaire (PDQ) [ Time Frame: Baseline and Week 52 ]
    Peyronie's disease bother score range 0 (no issue or not at all bothered) to 4 (extremely bothered) on 4 questions; total score range 0 to 16. A decrease in the change from baseline total score in the Peyronie's disease bother domain of the PDQ is indicated by a negative number.


Original Primary Outcome:

  • Change From Baseline in the Peyronie's Disease Bother Domain of the Peyronie's Disease Questionnaire (PDQ) [ Time Frame: Week 52 ]
  • Percent improvement from baseline in penile curvature [ Time Frame: Week 52 ]


Current Secondary Outcome:

  • A Responder Analysis Based on Subject Overall Global Assessment [ Time Frame: Week 52 ]
    Subject overall global assessment of Peyronie's disease score range -3 (much worse) to 3 (much improved). A score of 1 (improved in a small but important way), 2 (moderately improved), or 3 indicated a responder.
  • Change From Baseline in the Severity of Peyronie's Disease Symptoms Domain of the PDQ [ Time Frame: Baseline and Week 52 ]
    Peyronie's disease symptoms (physical and psychological) severity score range 0 (none) to 4 (very severe) on 6 questions; total score range 0 to 24. A decrease in the change from baseline total score in the Peyronie's disease symptoms domain of the PDQ is indicated by a negative number.
  • Change in the Overall Satisfaction Domain of the International Index of Erectile Function (IIEF) [ Time Frame: Baseline and Week 52 ]
    Overall satisfaction domain of the IIEF score range 0 to 5 on 2 questions where higher scores indicate improved function or satisfaction; total score range 0 to 10.
  • Change From Baseline in Penile Plaque Consistency [ Time Frame: Baseline and Week 52 ]
    Penile plaque consistency score range 1 (non-palpable) to 5 (hard). A decrease in the change from baseline score in penile plaque consistency is indicated by a negative number.
  • Change From Baseline in Penile Length [ Time Frame: Baseline and Week 52 ]
    A negative value represents a reduction in measurement from baseline.
  • Change From Baseline in the Penile Pain Domain of the PDQ in Subjects With Baseline Penile Pain Score ≥4 [ Time Frame: Baseline and Week 52 ]
    Penile pain scale range 0 (no pain) to 10 (extreme pain) on 3 questions; total score range 0 to 30. A decrease in the change from baseline total score in the penile pain domain of the PDQ is indicated by a negative number. Subjects were required to have a penile pain score of 4 or greater at baseline.
  • A Composite Responder Analysis Based on Change From Baseline in Penile Curvature and in the Peyronie's Disease Bother Score [ Time Frame: Week 52 ]

    A composite responder is indicated by

    • a percent reduction from baseline in penile curvature greater than or equal to the threshold, and
    • a reduction from baseline in Peyronie's disease bother score greater than or equal to the threshold, or change in the overall sexual activity within the last 3 months to having vaginal intercourse from no vaginal intercourse at screening.


Original Secondary Outcome:

  • Change from baseline in the severity of Peyronie's disease physical symptoms [ Time Frame: Week 52 ]
  • Change in the penile pain domain of the PDQ in subjects with penile pain score of 4 at baseline [ Time Frame: Week 52 ]
  • A responder analysis based on subject global assessment [ Time Frame: Week 52 ]
  • Change in the Overall Satisfaction Domain of the International Index of Erectile Function (IIEF) [ Time Frame: Week 52 ]
  • Change in penile plaque consistency [ Time Frame: Week 52 ]
  • Change in penile length [ Time Frame: Week 52 ]
  • Change from baseline in the severity of Peyronie's disease psychological symptoms [ Time Frame: Week 52 ]


Information By: Endo Pharmaceuticals

Dates:
Date Received: October 8, 2010
Date Started: October 2010
Date Completion:
Last Updated: September 7, 2016
Last Verified: July 2016