Study of AA4500 in the Treatment of Peyronie's Disease

Endo Pharmaceuticals

Status and phase

Completed

Phase 3

Conditions

Peyronie's Disease

Treatments

Biological: AA4500

Biological: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT01221597

AUX-CC-803

Details and patient eligibility

About

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 400 (267 AA4500 and 133 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 deformity (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 further treatment is not clinically indicated, 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.

Enrollment

418 patients

Sex

Male

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

Be a male and be ≥ 18 years of age
Be in a stable relationship with a female partner/spouse for at least 3 months before screening and be willing to have vaginal intercourse with that partner/spouse
Have symptom(s) of Peyronie's disease for at least 12 months before the first dose of study drug and have evidence of stable disease as determined by the investigator
Have curvature deformity 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
Be judged to be in good health, based upon the results of a medical history, physical examination, and laboratory profile
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
Be able to read, complete and understand the various rating instruments in English

Exclusion criteria

Has a penile curvature of less than 30° or greater than 90° at the screening visit
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 curvature deformity
- 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)
Has previously undergone surgery for Peyronie's disease
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 (PGE1) or trimix
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
Has an isolated hourglass deformity of the penis
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
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
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, pentoxifylline, over-the-counter erectile dysfunction medications, or steroidal anti-inflammatory drugs) 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
Has had extracorporeal shock wave therapy (ESWT) for correction of Peyronie's disease within the 6-month period before screening or plans to have ESWT at any time during the study
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
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
Has significant erectile dysfunction that has failed to respond to oral treatment with phosphodiesterase type 5 (PDE5) inhibitors
Has a penile Duplex Doppler ultrasound evaluation at screening that shows compromised penile hemodynamics that in the opinion of the investigator is clinically significant
Has uncontrolled hypertension, as determined by the investigator
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
Is unwilling or unable to cooperate with the requirements of the study including completion of all scheduled study visits
Has received an investigational drug or treatment within 30 days before the first dose of study drug
Has a known systemic allergy to collagenase or any other excipient of AA4500
Has a known allergy to any concomitant medication required as per the protocol
Has received anticoagulant medication (except for ≤ 165 mg aspirin daily or ≤ 800 mg of over-the-counter non-steroidal anti-inflammatory drugs [NSAIDS] daily) during the 7 days before each dose of study drug
Has received any collagenase treatments within 30 days of the first dose of study drug
Has, at any time, received AA4500 for the treatment of Peyronie's disease