Peyronie's Disease
Conditions
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.
Interventions
DRUG100 units of Botulinum Toxin Type A
Approximately 20 to 30 injections of 100 units of BOTOX® given with a 20 gage needle directly into the penile plaque
Approximately 20 to 30 injections of 10cc of preservative free normal saline given with a 20 gage needle directly into the penile plaque
DRUG100 units Botulinum Toxin A
Approximately 20 to 30 injections of 100 units of BOTOX® given with a 20 gage needle directly into the penile plaque
Sponsors
Allergan
Mohit Khera
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Percent Change of Penile Curvature in Degrees | Baseline (Pre-Treatment Screening Visit) to end of treatment at week 16 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | Baseline (Pre-Treatment Screening Visit) to end of treatment at week 16 | 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 |
| Change in Penile Blood Flow for Diameter | Baseline (Pre-Treatment Screening Visit) to end of treatment at week 16 | 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 |
| Change in Penile Plaque Size | Baseline (Pre-Treatment Screening Visit) to end of treatment at week 16 | 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 |
| Changes in International Index of Erectile Function Scores (IIEF) | Baseline (Pre-Treatment Screening Visit) to end of treatment at week 16 | 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 : 1. Orgasmic Function (Questions 9, 10); Maximum score = 10, Minimum score = 0 2. Sexual Desire (Questions 11, 12); Maximum score = 10, Minimum score = 0 3. Intercourse Satisfaction (Questions 6, 7, 8); Maximum score = 15, Minimum score = 0 4. 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\* |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Experimental 100 units of Botulinum Toxin Type A Injection solution will consist of 100 units of BOTOX® in 10 cc of preservative free normal saline
\*Crossover subjects were added to Experimental Group for analysis\* | 6 |
| Placebo Comparator Normal saline Injection solution will consist of 10 cc preservative free normal saline.
Optional 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. | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | Experimental | Placebo Comparator | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 12 Participants |
| Age, Continuous | 58.86 years STANDARD_DEVIATION 4.741 | 57.83 years STANDARD_DEVIATION 3.71 | 58.38 years STANDARD_DEVIATION 4.154 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 6 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 5 Participants | 11 Participants |
| Region of Enrollment United States | 6 participants | 6 participants | 12 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 6 |
| other Total, other adverse events | 5 / 10 | 0 / 6 |
| serious Total, serious adverse events | 0 / 10 | 0 / 6 |
Outcome results
Primary
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
Time frame: Baseline (Pre-Treatment Screening Visit) to end of treatment at week 16
Population: \*Crossover subjects were added to Experimental Group for analysis\*
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental | Average Percent Change of Penile Curvature in Degrees | -21.73 percent change | Standard Deviation 57.69 |
| Placebo Comparator | Average Percent Change of Penile Curvature in Degrees | 2.429 percent change | Standard Deviation 81.59 |
p-value: 0.5154t-test, 2 sided
Secondary
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
Time frame: Baseline (Pre-Treatment Screening Visit) to end of treatment at week 16
Population: \*Penile Doppler ultrasound was not performed on optional crossover patients. Data reflects scores derived from Experimental and Placebo group analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental | Change in Penile Blood Flow for Diameter | 5 minute left diameter | -0.75330 cm | Standard Deviation 2.551 |
| Experimental | Change in Penile Blood Flow for Diameter | Pre injection left diameter | 0.04167 cm | Standard Deviation 0.5869 |
| Experimental | Change in Penile Blood Flow for Diameter | 15 minute right diameter | -1.43700 cm | Standard Deviation 3.952 |
| Experimental | Change in Penile Blood Flow for Diameter | 5 minute right diameter | 1.34200 cm | Standard Deviation 4.006 |
| Experimental | Change in Penile Blood Flow for Diameter | 15 minute left diameter | -0.43500 cm | Standard Deviation 2.571 |
| Experimental | Change in Penile Blood Flow for Diameter | Pre injection right Diameter | -0.29 cm | Standard Deviation 0.8539 |
| Placebo Comparator | Change in Penile Blood Flow for Diameter | 15 minute left diameter | -0.1867 cm | Standard Deviation 1.203 |
| Placebo Comparator | Change in Penile Blood Flow for Diameter | Pre injection right Diameter | 0.1700 cm | Standard Deviation 0.7208 |
| Placebo Comparator | Change in Penile Blood Flow for Diameter | 5 minute right diameter | 0.2917 cm | Standard Deviation 0.6719 |
| Placebo Comparator | Change in Penile Blood Flow for Diameter | 5 minute left diameter | 0.0750 cm | Standard Deviation 0.9 |
| Placebo Comparator | Change in Penile Blood Flow for Diameter | 15 minute right diameter | -0.3550 cm | Standard Deviation 0.6469 |
| Placebo Comparator | Change in Penile Blood Flow for Diameter | Pre injection left diameter | 0.3983 cm | Standard Deviation 0.4565 |
Comparison: This will be a pilot study; it was assessed that 10 subjects in each arm, for a total of 20 subjects, will allow us to determine if the therapy is effective. To allow for screen failures, 45 subjects are planned for screening.p-value: 0.0166t-test, 2 sided
Secondary
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
Time frame: Baseline (Pre-Treatment Screening Visit) to end of treatment at week 16
Population: \*Penile Doppler ultrasound was not performed on optional crossover patients. Data reflects scores derived from Experimental and Placebo group analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental | Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | Pre injection Right PSV | -0.65670 cm/s | Standard Deviation 5.505 |
| Experimental | Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | Pre injection Right EDV | -2.10200 cm/s | Standard Deviation 6.798 |
| Experimental | Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | Pre injection Left PSV | -1.263 cm/s | Standard Deviation 9.032 |
| Experimental | Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | Pre injection Left EDV | -10.27 cm/s | Standard Deviation 8.261 |
| Experimental | Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | 5 minutes right PSV | 5.185 cm/s | Standard Deviation 28.48 |
| Experimental | Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | 5 minutes right EDV | -11.05 cm/s | Standard Deviation 19.56 |
| Experimental | Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | 5 minutes left psv | 2.863 cm/s | Standard Deviation 17.68 |
| Experimental | Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | 5 minutes left edv | -2.4 cm/s | Standard Deviation 10.8 |
| Experimental | Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | 15 minutes right PSV | 6.917 cm/s | Standard Deviation 20.91 |
| Experimental | Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | 15 minutes right EDV | -10.22 cm/s | Standard Deviation 22.82 |
| Experimental | Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | 15 minutes left PSV | 7.183 cm/s | Standard Deviation 10.81 |
| Experimental | Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | 15 minutes left EDV | -2.267 cm/s | Standard Deviation 11.58 |
| Placebo Comparator | Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | 15 minutes left PSV | -15.10 cm/s | Standard Deviation 40.93 |
| Placebo Comparator | Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | Pre injection Right PSV | -9.0170 cm/s | Standard Deviation 11.43 |
| Placebo Comparator | Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | 5 minutes left psv | -6.6830 cm/s | Standard Deviation 22.76 |
| Placebo Comparator | Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | Pre injection Right EDV | -0.8667 cm/s | Standard Deviation 3.771 |
| Placebo Comparator | Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | 15 minutes right EDV | 1.55 cm/s | Standard Deviation 5.001 |
| Placebo Comparator | Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | Pre injection Left PSV | -6.4330 cm/s | Standard Deviation 12.04 |
| Placebo Comparator | Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | 5 minutes left edv | 3.5 cm/s | Standard Deviation 10.16 |
| Placebo Comparator | Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | Pre injection Left EDV | -6.75 cm/s | Standard Deviation 11.63 |
| Placebo Comparator | Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | 15 minutes left EDV | 3.367 cm/s | Standard Deviation 6.046 |
| Placebo Comparator | Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | 5 minutes right PSV | 2.1330 cm/s | Standard Deviation 6.425 |
| Placebo Comparator | Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | 15 minutes right PSV | -15.52 cm/s | Standard Deviation 34.44 |
| Placebo Comparator | Change in Penile Blood Flow for Peak Systolic Velocity (PSV) and End-diastolic Velocity (EDV) | 5 minutes right EDV | -0.1417 cm/s | Standard Deviation 3.944 |
Comparison: This will be a pilot study; it was assessed that 10 subjects in each arm, for a total of 20 subjects, will allow us to determine if the therapy is effective. To allow for screen failures, 45 subjects are planned for screening.~This analysis pertains to both categoriesp-value: 0.3009t-test, 2 sided
Secondary
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
Time frame: Baseline (Pre-Treatment Screening Visit) to end of treatment at week 16
Population: \*Crossover subjects were added to Experimental Group for analysis\*
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental | Change in Penile Plaque Size | screening visit | 717.5 cubic millimeters | Standard Deviation 827.4 |
| Experimental | Change in Penile Plaque Size | week 16 | 198.9 cubic millimeters | Standard Deviation 220.8 |
| Placebo Comparator | Change in Penile Plaque Size | screening visit | 485.8 cubic millimeters | Standard Deviation 599.6 |
| Placebo Comparator | Change in Penile Plaque Size | week 16 | 319.0 cubic millimeters | Standard Deviation 252.2 |
Comparison: This will be a pilot study; it was assessed that 10 subjects in each arm, for a total of 20 subjects, will allow us to determine if the therapy is effective. To allow for screen failures, 45 subjects are planned for screening.p-value: 0.8566t-test, 2 sided
Secondary
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 : 1. Orgasmic Function (Questions 9, 10); Maximum score = 10, Minimum score = 0 2. Sexual Desire (Questions 11, 12); Maximum score = 10, Minimum score = 0 3. Intercourse Satisfaction (Questions 6, 7, 8); Maximum score = 15, Minimum score = 0 4. 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\*
Time frame: Baseline (Pre-Treatment Screening Visit) to end of treatment at week 16
Population: \*Crossover subjects were added to Experimental Group for analysis\*
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental | Changes in International Index of Erectile Function Scores (IIEF) | Screening Visit | 15.60 score on a scale | Standard Deviation 11.75 |
| Experimental | Changes in International Index of Erectile Function Scores (IIEF) | Week 16 | 17.20 score on a scale | Standard Deviation 11.61 |
| Placebo Comparator | Changes in International Index of Erectile Function Scores (IIEF) | Screening Visit | 21 score on a scale | Standard Deviation 12.13 |
| Placebo Comparator | Changes in International Index of Erectile Function Scores (IIEF) | Week 16 | 21.50 score on a scale | Standard Deviation 11.74 |
Comparison: This will be a pilot study; it was assessed that 10 subjects in each arm, for a total of 20 subjects, will allow us to determine if the therapy is effective. To allow for screen failures, 45 subjects are planned for screening.p-value: 0.0286t-test, 2 sided