The Safety and Effectiveness of AA4500 in Subjects With Peyronie's Disease

A Phase 2b, Double-Blind, Randomized, Placebo-Controlled Study of the Safety and Effectiveness of AA4500 Administered Two Times a Week for Up to Three Treatment Cycles (2 x 3) in Subjects With Peyronie's Disease

This study evaluated the safety and effectiveness of AA4500 in improving the impact of Peyronie's disease on quality of life and improving penile curvature in men with Peyronie's disease

Study Overview

• Status: Completed
• Conditions: Peyronie's Disease
• Intervention / Treatment: Biological: AA4500; Biological: Placebo

Detailed Description

A Phase 2b randomized, double-blind, placebo-controlled study of AA4500 in the treatment of subjects with Peyronie's disease.

During the screening period, subjects had a physical examination including body weight and height, vital sign measurements, a 12-lead electrocardiogram (ECG), and clinical laboratory testing. Medical history, prior and concomitant medications, and demographic data were recorded.

• Study Type: Interventional
• Enrollment (Actual): 147
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Burbank, California, United States, 91505
      • Urology Associates Medical Group
  • Connecticut
    • Middlebury, Connecticut, United States, 06762
      • Urology Specialists Connecticut Clinical Research Center, LLC
    • New Haven, Connecticut, United States, 06511
      • The Urology Center, PC
  • Florida
    • Aventura, Florida, United States, 33180
      • South Florida Medical Research
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Urology Specialists, SC
  • Indiana
    • Fort Wayne, Indiana, United States, 46825
      • Northeast Indiana Research, LLC
    • Jeffersonville, Indiana, United States, 47130
      • Metropolitan Urology, PSC
  • New York
    • Brooklyn, New York, United States, 11219
      • Maimonides Medical Center Divison of Urology
    • New York, New York, United States, 10016
      • University Urology Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • Tristate Urologic Services
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine, Scott Department of Urology
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Urology of Virginia (a division of Sentara Medical Group)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Heterosexual male ≥ 18 years of age
• In a stable relationship with a partner/spouse for at least 3 months before screening
• Have a diagnosis of Peyronie's disease for at least 6 months before first dose of study drug
• Have a penile curvature of at least 30° in the dorsal, lateral, or dorsal/lateral plane
• Have functional difficulty related to Peyronie's disease (eg, difficulty with intromission or erectile dysfunction)
• Be judged to be in good health based upon the results of medical history, physical examination and laboratory profile
• Voluntarily sign an informed consent agreement approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC). The subject must have also signed an authorization form to allow disclosure of his protected health information. The protected health information authorization form and informed consent form may have been an integrated form or may have been separate forms, depending on the institution
• Be able to complete and understand the various rating instruments

Exclusion Criteria:

• Have had an average of three successive blood pressure readings ≥ 160/100 mmHg during screening or the Day 1 assessments
• Severe pain during penile palpation

• Any of the following conditions:

  • Chordee in the presence or absence of hypospadias
  • Thrombosis of the dorsal penile artery
  • 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 sexually transmitted disease
  • Known Hepatitis B or C
  • Known immune deficiency disease or be positive for human immunodeficiency virus (HIV)
• Previously undergone surgery for Peyronie's disease
• Penile curvature of less than 30° or greater than 90°
• Failed to have a rigid erection after pharmacological stimulation with a vasoactive injection of Prostaglandin E1 10 to 20 µg, which, in the opinion of the investigator, was sufficient to accurately measure the subject's penile deformity
• Had a calcified plaque as evident by appropriate radiographic evaluation, penile x-ray, or penile ultrasound. Non-contiguous stippling of calcium was acceptable for inclusion
• Had an isolated hourglass deformity of the penis without curvature
• Had the plaque causing curvature of the penis located proximal to the base of the penis, so that the injection of the local anesthetic would have interfered with the injection of AA4500 into the plaque
• 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
• Received alternative medical therapies for Peyronie's disease administered by the oral (including, but not limited to, vitamin E (>500IU), 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 4 weeks before the first dose of study drug or plans to use any of these medical therapies at any time during the study
• 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
• 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
• Significant erectile dysfunction that has failed to respond to oral treatment with phosphodiesterase type 5 (PDE5) inhibitors
• Recent history of stroke, bleeding, or other medical condition, which in the investigator's opinion would make the subject unsuitable for enrollment in the study
• Unwilling or unable to cooperate with the requirements of the study including completion of all scheduled study visits
• Received an investigational drug or treatment within 30 days before the first dose of study drug
• Allergy to collagenase or any other excipient of AA4500
• Allergy to any concomitant medication required as per the protocol
• Received anticoagulant medication (except for ≤ 165 mg aspirin daily or ≤ 800 mg of over-the-counter NSAIDS daily) during the 7 days before each dose of study drug
• Received doxycycline or a tetracycline derivative during the 7 days before each dose of study drug or plans to use these drugs within 2 days after the injection of study drug
• Received any collagenase treatments within 30 days of the first dose of study drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Biological: Placebo; 2 single injections of study drug per each treatment series up to three treatment series total in study. Each treatment series is separated by 6 weeks.
Experimental: AA4500; Clostridial collagenase for injection	Biological: AA4500; 2 single injections of study drug per each treatment series up to three treatment series total in study. Each treatment series was separated by 6 weeks.; Other Names: Clostridial collagenase for injection (AA4500)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Penile Curvature	Negative change reflects improvement in penile curvature	Baseline and Week 36 or last observation carried forward (LOCF)
Change From Baseline in Peyronie's Disease Questionnaire (PDQ) Peyronie's Disease Symptom Bother	Peyronie's disease Symptom Bother Scale: 0-20 lower numbers reflect 'less symptom bother'; higher numbers reflect 'more symptom bother' Change from baseline equals Week 36 minus baseline. Negative change reflects improvement in the symptom bother scale.	Baseline to Week 36 or LOCF
Change From Baseline in PDQ Intercourse Contraint	Peyronie's disease intercourse contraint Scale: 0-12 lower numbers reflect 'less intercourse contraint'; higher numbers reflect 'more intercourse constraint' Change from baseline equals Week 36 minus baseline. Negative change reflects improvement in the intercourse constraint scale.	Baseline to Week 36 or LOCF
Change From Baseline in PDQ Intercourse Discomfort	Peyronie's disease intercourse discomfort Scale: 0-15 lower numbers reflect 'less intercourse discomfort'; higher numbers reflect 'more intercourse discomfort' Change from baseline equals Week 36 minus baseline. Negative change reflects improvement in the intercourse discomfort scale.	Baseline to Week 36 or LOCF
Change From Baseline in PDQ Penile Pain	Peyronie's disease penile pain Scale: 0-40 lower numbers reflect 'less penile pain'; higher numbers reflect 'more penile pain' Change from baseline=Week 36 minus baseline. Negative change reflects improvement in the penile pain scale.	Baseline to Week 36 or LOCF

Collaborators and Investigators

• Sponsor: Endo Pharmaceuticals
• Investigators: Study Director: Veronica Urdaneta, MD, Endo Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: September 16, 2008
• First Submitted That Met QC Criteria: September 17, 2008
• First Posted (Estimate): September 18, 2008

Study Record Updates

• Last Update Posted (Actual): October 5, 2017
• Last Update Submitted That Met QC Criteria: September 7, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: penile curvature; Peyronie's disease; penile plaque
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Penile Diseases; Penile Induration
• Other Study ID Numbers: AUX-CC-801