H-22411: BOTOX® for Peyronie's Disease

Study Overview
=================
Brief Summary
-----------------
Peyronie's disease is a condition in which a plaque, or hard lump, forms on the penis. It causes hardened tissue, pain, and an abnormal bending in the penis. These symptoms are more severe during an erection. Significant bending of the penis can result in pain, poor erections, and an inability to engage in sexual intercourse. This disease affects about 3% of the male population. The average age of onset of this disease is 57 years old. The cause of the disease is unknown. However, many believe that it may be due to trauma to the penis (such as injury or extremely vigorous sexual activity).

Detailed Description
-----------------
Treatments for this disease have been limited and often unsuccessful. The goal of treatment is to reduce pain and maintain sexual function. Oral medicines that prevent plaque formation and promote plaque breakdown have not been effective. Many patients with the disease will require injections of medicines directly into the plaque. These injections have been used for over 50 years in the treatment of major Peyronie's disease. The disease often resolves on its own without treatment. Surgery may be performed to remove hardened tissue in the penis. However, surgery is not done during the first 12 months of the disease. There are 2 phases of the disease: the active phase and the inactive phase. The active phase usually occurs during the first 12 months of the disease. The stabilization of the plaque is known as the inactive phase. We are inviting men with stable disease to take part in this study which will test BOTOX® versus a placebo (a placebo contains no medicine). This will be a randomized, placebo-controlled, cross-over, single-center trial. The placebo group has the option to cross over to the treatment arm (ARM 1) of the study at the end of their 16 weeks of placebo arm (ARM 2). Study drug is Botulinum toxin type A (BOTOX®). Subjects who meet the inclusion criteria for the study will be randomized to either the treatment or placebo arm. Treatment: Injection solution will consist of 100 units of BOTOX® in 10 cc of preservative free normal saline, or Placebo: Injection solution will consist of 10 cc preservative free normal saline.

Official Title
-----------------
The Efficacy of Botulinum Toxin Type a in Treating Peyronie's Disease

Conditions
-----------------
Peyronie's Disease

Intervention / Treatment
-----------------
* Drug: 100 units of Botulinum Toxin Type A
* Other: Preservative free normal saline
* Drug: 100 units Botulinum Toxin A


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects with stable Peyronie's plaques. Males at least 18 years of age Must give informed consent. Exclusion Criteria: Subjects in the active phase of Peyronie's disease. Subjects with less than 1 year history of Peyronie's disease. Subjects taking oral medications for Peyronie's disease which include Trental, Viagra, vitamin E, colchicines, L-arginine, and tamoxifen. There will be a 2 week wash-out period if patients are on these medications. Subjects with more than 1 penile plaque will be excluded from the study. Subjects with calcified plaques demonstrated by ultrasound will be excluded from the study. Known allergy or sensitivity to any components of the study medication (botulinum toxin A), anesthetics, or any other product associated with the treatment and general study procedures. Any medical condition or neuromuscular disorder that may put the patient at increased risk with exposure to botulinum toxin A (BTX-A), including myasthenia gravis, Eaton-Lambert syndrome, or amyotrophic lateral sclerosis. Patient taking aminoglycosides or any drug known to interfere with neuromuscular transmission. Patient has hemophilia or other clotting factor deficiencies or disorders that cause bleeding diathesis. Patient must not be taking aspirin, non-steroidal anti-inflammatory drugs, or Coumadin for 7 or more days prior to Botox injection. Episode of unstable angina pectoris, myocardial infarction, transient ischemic attack, or cerebrovascular accident within the past 6 months.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 100 units of Botulinum Toxin Type A<br>Injection solution will consist of 100 units of BOTOX® in 10 cc of preservative free normal saline | Drug: 100 units of Botulinum Toxin Type A<br>* Approximately 20 to 30 injections of 100 units of BOTOX® given with a 20 gage needle directly into the penile plaque<br>* Other names: BOTOX®;|
| Placebo Comparator: Normal saline<br>Injection solution will consist of 10 cc preservative free normal saline Subjects had the choice of crossing over to ARM 1 at the end of 16 weeks. Cross-over: For subjects in Arm 2, crossover to BOTOX treatment will begin after the Week 16 Visit by repeating the study schedule as for Week 0 to Week 16. | Other: Preservative free normal saline<br>* Approximately 20 to 30 injections of 10cc of preservative free normal saline given with a 20 gage needle directly into the penile plaque<br>Drug: 100 units Botulinum Toxin A<br>* Approximately 20 to 30 injections of 100 units of BOTOX® given with a 20 gage needle directly into the penile plaque<br>* Other names: Cross-over;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Percent Change of Penile Curvature in Degrees | Measured by a protractor from pictures taken at baseline (pre-treatment screening visit) and end of treatment at week 16 *Crossover subjects were added to Experimental Group for analysis* Negative value equates to a reduction in curvature Positive value equates to an increase in curvature | Baseline (Pre-Treatment Screening Visit) to end of treatment at week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | Results of penile doppler ultrasound from baseline/screening visit to end of treatment at week 16 will be compared. peak systolic velocity (PSV) and end-diastolic velocity (EDV) are assessed here. Change is calculated as week 16 values - screening visit values Negative values are a decrease in velocity Positive values are an increase in velocity | Baseline (Pre-Treatment Screening Visit) to end of treatment at week 16 | 
| Change in Penile Blood Flow for Diameter | Results of penile doppler ultrasound from the baseline/screening visit to end of treatment at week 16 will be compared. Diameter is assessed here. Change is calculated as week 16 values - screening visit values Negative values are a decrease in diameter Positive values are an increase in diameter | Baseline (Pre-Treatment Screening Visit) to end of treatment at week 16 | 
| Change in Penile Plaque Size | Results of ultrasound at baseline/screening visit to end of treatment at week 16 will be compared. *Crossover subjects were added to Experimental Group for analysis* Change is calculated as week 16 values values minus screening visit values Increase in value equates to increased plaque size Decrease in value equates to decreased plaque size | Baseline (Pre-Treatment Screening Visit) to end of treatment at week 16 | 
| Changes in International Index of Erectile Function Scores (IIEF) | Subject's average scores on IIEF at baseline/screening visit to end of treatment at week 16 are compared The subscale measures self-reported erectile function. Maximum score is 30, Minimum is 0. A score of 0 is the absolute best outcome. A score of 30 is the absolute worst outcome. Erectile Function score is a summation of questions 1,2,3,4, and 15. This study is assessing their erectile function and not the other subscales. The other subscale scores are : Orgasmic Function (Questions 9, 10); Maximum score = 10, Minimum score = 0 Sexual Desire (Questions 11, 12); Maximum score = 10, Minimum score = 0 Intercourse Satisfaction (Questions 6, 7, 8); Maximum score = 15, Minimum score = 0 Overall Satisfaction (Question 13, 14): Maximum score = 10, Minimum score = 0 Subscales are not combined to make a total composite score. *Crossover subjects were added to Experimental Group for analysis* | Baseline (Pre-Treatment Screening Visit) to end of treatment at week 16 |