Peyronie's Disease
Conditions
Keywords
Peyronie's disease, penile plaque, penile curvature
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.
Interventions
BIOLOGICALAA4500
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.
BIOLOGICALPlacebo
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.
Sponsors
Endo Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Penile Curvature | Baseline and Week 36 or last observation carried forward (LOCF) | Negative change reflects improvement in penile curvature |
| Change From Baseline in Peyronie's Disease Questionnaire (PDQ) Peyronie's Disease Symptom Bother | Baseline to Week 36 or LOCF | 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. |
| Change From Baseline in PDQ Intercourse Contraint | Baseline to Week 36 or LOCF | 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. |
| Change From Baseline in PDQ Intercourse Discomfort | Baseline to Week 36 or LOCF | 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. |
| Change From Baseline in PDQ Penile Pain | Baseline to Week 36 or LOCF | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AA4500 Clostridial collagenase for injection 0.58 mg. Study drug was injected directly into the penile plaque (point of maximal concavity as determined by a standard method) of the flaccid penis. Subjects could recieve up to 3 treatment series. During each treatment series, subjects will receive 2 injections of study drug with at least 24 hours but not more than 72 hours between injections. | 111 |
| Placebo Placebo was injected directly into the penile plaque (point of maximal concavity as determined by a standard method) of the flaccid penis. Subjects could recieve up to 3 treatment series. During each treatment series, subjects will receive 2 injections of study drug with at least 24 hours but not more than 72 hours between injections. | 36 |
| Total | 147 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Protocol Violation | 2 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | Placebo | AA4500 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 16 Participants | 18 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants | 95 Participants | 129 Participants |
| Age, Continuous | 55.4 years STANDARD_DEVIATION 6.95 | 56.9 years STANDARD_DEVIATION 7.79 | 56.6 years STANDARD_DEVIATION 7.6 |
| Region of Enrollment United States | 36 participants | 111 participants | 147 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 36 Participants | 111 Participants | 147 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 109 / 111 | 28 / 36 |
| serious Total, serious adverse events | 4 / 111 | 1 / 36 |
Outcome results
Primary
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.
Time frame: Baseline to Week 36 or LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 | Change From Baseline in PDQ Intercourse Contraint | -1.5 scores on a scale | Standard Deviation 3.31 |
| Placebo | Change From Baseline in PDQ Intercourse Contraint | -0.7 scores on a scale | Standard Deviation 3.65 |
p-value: 0.164ANOVA
Primary
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.
Time frame: Baseline to Week 36 or LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 | Change From Baseline in PDQ Intercourse Discomfort | -0.8 scores on a scale | Standard Deviation 3.46 |
| Placebo | Change From Baseline in PDQ Intercourse Discomfort | -0.4 scores on a scale | Standard Deviation 4.27 |
p-value: 0.442ANOVA
Primary
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.
Time frame: Baseline to Week 36 or LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 | Change From Baseline in PDQ Penile Pain | -2.4 scores on a scale | Standard Deviation 6.32 |
| Placebo | Change From Baseline in PDQ Penile Pain | -0.5 scores on a scale | Standard Deviation 5.3 |
p-value: 0.095ANOVA
Primary
Change From Baseline in Penile Curvature
Negative change reflects improvement in penile curvature
Time frame: Baseline and Week 36 or last observation carried forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 | Change From Baseline in Penile Curvature | -29.7 Percent change from baseline | Standard Deviation 27.16 |
| Placebo | Change From Baseline in Penile Curvature | -11.0 Percent change from baseline | Standard Deviation 30.87 |
p-value: 0.001ANOVA
Primary
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.
Time frame: Baseline to Week 36 or LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 | Change From Baseline in Peyronie's Disease Questionnaire (PDQ) Peyronie's Disease Symptom Bother | -2.6 scores on a scale | Standard Deviation 4.63 |
| Placebo | Change From Baseline in Peyronie's Disease Questionnaire (PDQ) Peyronie's Disease Symptom Bother | -0.8 scores on a scale | Standard Deviation 3.63 |
p-value: 0.046ANOVA