Clinical trial NCT01685437: A Phase 3, Open-label 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 Peyronie's Disease
Official title: A Phase 3, Open-label 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 Peyronie's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Peyronie's Disease
Keywords: Peyronie's disease, penile plaque, penile curvature
Lead sponsor: Endo Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2012-09-14
Enrollment: 189
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is a Phase 3, open-label study of the safety and efficacy of AA4500 0.58 mg in subjects with Peyronie's disease. Subjects will be screened for study eligibility within 21 days before the initial injection of study drug in the first treatment cycle. Enrollment will include all subjects who meet the eligibility criteria and who received placebo and completed one of the Auxilium-sponsored studies AUX-CC-803 or AUX-CC-804.

Detailed description: After the final injection of each treatment cycle, the investigator or qualified designee (ie, qualified by license, education, and training to perform the study procedure according to local, state, and country requirements) will model the plaque in an attempt to stretch or elongate the plaque. If the subject's penile curvature is reduced to \<15° 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 168 (± 7 days) and 252 (± 7 days) (nominal weeks 24 and 36).

Eligibility criteria: Inclusion Criteria:

No subject should be enrolled until all eligibility criteria have been satisfied. Subjects who completed their participation in Auxilium-sponsored studies AUX-CC-803 or AUX-CC-804 and received placebo in that study may enroll in this study provided they continue to meet the eligibility requirements. To qualify for the study a subject must:

1. Have penile curvature of at least 30° in the dorsal, lateral, or dorsal/lateral plane at screening. It must be possible to delineate the single plane of maximal curvature for evaluation during the study
2. Be judged to be in good health, based upon the results of a medical history, physical examination,and laboratory profile
3. Have participated in Study AUX-CC-803 or Study AUX-CC-804, received placebo in that study,and completed that study
4. Voluntarily sign and date an informed consent agreement approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC). The subject must also sign an authorization form to allow disclosure of his protected health information (PHI). The PHI authorization form and informed consent form may be an integrated form or may be separate forms depending on the institution
5. Be able to read, complete and understand the various rating instruments in English.

Exclusion Criteria:

A subject will be excluded from study participation if he:

1. Has a penile curvature of less than 30° or greater than 90° at the screening visit
2. Has any of the following conditions:

   * Chordee in the presence or absence of hypospadias
   * Thrombosis of the dorsal penile artery and/or vein
   * Infiltration by a benign or malignant mass resulting in penile curvature
   * Infiltration by an infectious agent, such as lymphogranuloma venereum
   * Ventral curvature from any cause
   * Presence of an active sexually transmitted disease
   * Known active hepatitis B or C
   * Known immune deficiency disease or be positive for human immunodeficiency virus (HIV)
3. Has previously undergone surgery for Peyronie's disease
4. Fails to have an erection which in the opinion of the investigator is sufficient to accurately measure the subject's penile deformity after administration of prostaglandin E1 or trimix or another suitable injectable pharmacologic stimulant according to the standard practice at the investigator's institution
5. Has a calcified plaque as evident by appropriate radiographic evaluation, penile x-ray or penile ultrasound that would prevent proper injection of study medication. Non-contiguous stippling of calcium is acceptable for inclusion provided the calcium deposit does not interfere with the injection of AA4500 into the plaque
6. Has an isolated hourglass deformity of the penis
7. Has the plaque causing curvature of the penis located proximal to the base of the penis, so that the injection of the local anesthetic would interfere with the injection of AA4500 into the plaque
8. Has previously received alternative medical therapies for Peyronie's disease administered by the intralesional route (including, but not limited to, steroids, verapamil, and the naturally occurring low molecular weight protein, interferon-α2b) within 3 months before the first dose of study drug or plans to use any of these medical therapies at any time during the study
9. Has received alternative medical therapies for Peyronie's disease administered by the oral (including, but not limited to, vitamin E \[\>500 U\], potassium aminobenzoate \[Potaba\], tamoxifen, colchicine, and pentoxifylline, ,) or topical routes (including, but not limited to, verapamil applied as a cream) within 3 months before the first dose of study drug or plans to use any of these medical therapies at any time during the study
10. Has had extracorporeal shock wave therapy (ESWT) for the correction of Peyronie's disease within the 6-month period before screening or plans to have ESWT at any time during the study
11. Has used any mechanical type device for correction of Peyronie's disease within the 2-week period before screening or plans to use any these devices at any time during the study
12. Has used a mechanical device to induce a passive erection within the 2-week period before screening or plans to use any of these devices at any time during the study
13. Has significant erectile dysfunction that has failed to respond to oral treatment with phosphodiesterase type 5 (PDE5) inhibitors
14. Has a penile Duplex Doppler ultrasound evaluation at screening that shows compromised penile hemodynamics that in the opinion of the investigator is clinically significant
15. Has uncontrolled hypertension, as determined by the investigator
16. Has a known recent history of stroke, bleeding, or other significant medical condition, which in the investigator's opinion would make the subject unsuitable for enrollment in the study
17. Has received an investigational drug or treatment within 30 days before the first dose of study drug, except for placebo in Studies AUX-CC-803 or AUX-CC-804
18. Has a known systemic allergy to collagenase or any other excipient of AA4500
19. Has a known allergy to any concomitant medication required as per the protocol
20. Has received anticoagulant medication (except for ≤ 150 mg aspirin daily) during the 7 days before each dose of study drug
21. Has received any collagenase treatments within 30 days of the first dose of study drug
22. Has, at any time, received AA4500 for the treatment of Peyronie's disease
23. Is unwilling or unable to cooperate with the requirements of the study including completion of all scheduled study visits

Primary outcomes:
measure: Percentage Change From Baseline in Penile Curvature
timeFrame: Baseline and Week 36
measure: Change From Baseline in the Peyronie's Disease Bother Domain of the Peyronie's Disease Questionnaire (PDQ)
timeFrame: Baseline and Week 36
Secondary outcomes:
measure: Change From Baseline in the Severity of Peyronie's Disease Symptoms Domain of the PDQ
timeFrame: Baseline and Week 36
measure: Change From Baseline in the Penile Pain Domain of the PDQ in Subjects With Baseline Penile Pain Score ≥4
timeFrame: Baseline and Week 36
measure: A Responder Analysis Based on Subject Overall Global Assessment
timeFrame: Week 36
measure: Change in the Overall Satisfaction Domain of the International Index of Erectile Function (IIEF)
timeFrame: Baseline and Week 36
measure: Change From Baseline in Penile Plaque Consistency
timeFrame: Baseline and Week 36
measure: A Composite Responder Analysis Based on Change From Baseline in Penile Curvature and in the Peyronie's Disease Bother Score
timeFrame: Week 36
measure: Change From Baseline in Penile Length
timeFrame: Baseline and Week 36
Other outcomes:
Locations:
Study officials:
affiliation: Auxilium Pharmaceuticals, Inc.
name: Gregory Kaufman, MD
role: STUDY_DIRECTOR
References: