Clinical trial NCT00755222: The Safety and Effectiveness of AA4500 in Subjects With Peyronie's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Peyronie's Disease
Keywords: Peyronie's disease
penile plaque
penile curvature
Lead sponsor: Endo Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2008-09-18
Enrollment: 147
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Penile Curvature
timeFrame: Baseline and Week 36 or last observation carried forward (LOCF)
measure: Change From Baseline in Peyronie's Disease Questionnaire (PDQ) Peyronie's Disease Symptom Bother
timeFrame: Baseline to Week 36 or LOCF
measure: Change From Baseline in PDQ Intercourse Contraint
timeFrame: Baseline to Week 36 or LOCF
measure: Change From Baseline in PDQ Intercourse Discomfort
timeFrame: Baseline to Week 36 or LOCF
measure: Change From Baseline in PDQ Penile Pain
timeFrame: Baseline to Week 36 or LOCF
Secondary outcomes:
Other outcomes:
Locations:
city: Burbank
country: United States
facility: Urology Associates Medical Group
state: California
city: Middlebury
country: United States
facility: Urology Specialists Connecticut Clinical Research Center, LLC
state: Connecticut
city: New Haven
country: United States
facility: The Urology Center, PC
state: Connecticut
city: Aventura
country: United States
facility: South Florida Medical Research
state: Florida
city: Chicago
country: United States
facility: Urology Specialists, SC
state: Illinois
city: Fort Wayne
country: United States
facility: Northeast Indiana Research, LLC
state: Indiana
city: Jeffersonville
country: United States
facility: Metropolitan Urology, PSC
state: Indiana
city: Brooklyn
country: United States
facility: Maimonides Medical Center Divison of Urology
state: New York
city: New York
country: United States
facility: University Urology Associates
state: New York
city: Cincinnati
country: United States
facility: Tristate Urologic Services
state: Ohio
city: Houston
country: United States
facility: Baylor College of Medicine, Scott Department of Urology
state: Texas
city: Norfolk
country: United States
facility: Urology of Virginia (a division of Sentara Medical Group)
state: Virginia
Study officials:
affiliation: Endo Pharmaceuticals
name: Veronica Urdaneta, MD
role: STUDY_DIRECTOR
References: