A Safety and Efficacy Study of OnabotulinumtoxinA in Premature Ejaculation

Study Overview
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Brief Summary
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This is a safety and efficacy study of OnabotulinumtoxinA for the treatment of premature ejaculation (PE) in male participants.

Detailed Description
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This is a phase 2, multicenter, randomized, double-blind, placebo-controlled, dose-escalation study to assess a range of doses of OnabotulinumtoxinA for the treatment of male participants with PE. Participants will attend a minimum of 6 or 7 clinic visits and also have 1 or 2 telephone visits. Partners will need to attend a clinic visit during the screening period to provide informed consent and to receive training on measurement and recording of the intravaginal ejaculatory latency time (IELT). Participants will be enrolled in cohorts. Within the first 5 cohorts, 8 participants are to receive OnabotulinumtoxinA and 2 participants to receive placebo. For cohort 6, 12 participants will receive OnabotulinumtoxinA and 12 participants will receive placebo. Participants will receive a single treatment of study medication delivered bilaterally to the bulbospongiosus muscle. The initial OnabotulinumtoxinA total dose in this dose escalation study will be 5 U and the maximum OnabotulinumtoxinA total dose will be 100 U. Upon request and if eligible, participants in cohort 6, will have the option to receive a second injection of OnabotulinumtoxinA (Open-label).

Official Title
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An Exploratory Study of the Safety and Efficacy of BOTOX® for the Treatment of Premature Ejaculation

Conditions
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Premature Ejaculation

Intervention / Treatment
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* Drug: OnabotulinumtoxinA
* Drug: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of premature ejaculation Stable monogamous sexual relationship with female partner for at least 6 months, and intends to continue with the same partner for the duration of the study Participant has ability to follow study instructions and complete study assessment tools Exclusion Criteria: Premature ejaculation caused by medical or surgical issues, or is related to stress or other issues (eg, relationship problems) Pain with ejaculation Planned use of topical penile treatments (eg, anesthetics, herbal treatments) or penile injections during the study Prior genital, prostatic or lower urinary tract surgery (other than vasectomy or circumcision) Previous or current usage of botulinum toxin therapy of any serotype for any urological condition Use of botulinum toxin therapy of any serotype for any nonurological condition (eg, cosmetic, chronic migraine) during the 12 weeks prior to screening, or planned usage during the study Diagnosis of Myasthenia gravis, Eaton-Lambert Syndrome, Amyotrophic Lateral Sclerosis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OnabotulinumtoxinA Dose 1<br>OnabotulinumtoxinA Dose 1 injected into specified muscle per protocol on Day 1. | Drug: OnabotulinumtoxinA<br>* OnabotulinumtoxinA injected into specified muscle per protocol on Day 1.<br>* Other names: Botulinum Toxin Type A;|
| Experimental: OnabotulinumtoxinA Dose 2<br>OnabotulinumtoxinA Dose 2 injected into specified muscle per protocol on Day 1. Participants were eligible for another treatment after 12 weeks. | Drug: OnabotulinumtoxinA<br>* OnabotulinumtoxinA injected into specified muscle per protocol on Day 1.<br>* Other names: Botulinum Toxin Type A;|
| Experimental: OnabotulinumtoxinA Dose 3<br>OnabotulinumtoxinA Dose 3 injected into specified muscle per protocol on Day 1. | Drug: OnabotulinumtoxinA<br>* OnabotulinumtoxinA injected into specified muscle per protocol on Day 1.<br>* Other names: Botulinum Toxin Type A;|
| Experimental: OnabotulinumtoxinA Dose 4<br>OnabotulinumtoxinA Dose 4 injected into specified muscle per protocol on Day 1. | Drug: OnabotulinumtoxinA<br>* OnabotulinumtoxinA injected into specified muscle per protocol on Day 1.<br>* Other names: Botulinum Toxin Type A;|
| Experimental: OnabotulinumtoxinA Dose 5<br>OnabotulinumtoxinA Dose 5 injected into specified muscle per protocol on Day 1. | Drug: OnabotulinumtoxinA<br>* OnabotulinumtoxinA injected into specified muscle per protocol on Day 1.<br>* Other names: Botulinum Toxin Type A;|
| Experimental: OnabotulinumtoxinA Dose 6<br>OnabotulinumtoxinA Dose 6 injected into specified muscle per protocol on Day 1. | Drug: OnabotulinumtoxinA<br>* OnabotulinumtoxinA injected into specified muscle per protocol on Day 1.<br>* Other names: Botulinum Toxin Type A;|
| Placebo Comparator: Placebo<br>Placebo (normal saline) injected into specified muscle per protocol on Day 1. | Drug: Normal Saline<br>* Placebo (normal saline) injected into specified muscle per protocol on Day 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Geometric Mean Intravaginal Ejaculatory Latency Time (IELT) | IELT, the time from vaginal penetration to ejaculation, was measured by a stopwatch and was recorded in the sexual intercourse diary (SID). The Logarithm Value of the Geometric Mean of each individual participant's IELT recorded in the SID up to each time point was calculated. The mean and standard deviation (SD) of log-transformed geometric mean IELTs are then calculated for each treatment group. An Analysis of Covariance (ANCOVA) Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate was used for analyses. A positive change from Baseline indicates improvement. | Baseline (Day 1) to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Average IELT | IELT, the time from vaginal penetration to ejaculation, was measured by a stopwatch and was recorded in the SID. The average of each individual participant's IELT recorded in the SID up to each time point was calculated. The mean and SD of average IELTs were then calculated for each treatment group. An ANCOVA Model with treatment as the fixed effect and baseline average mean IELT as the covariate was used for analyses. A positive change from Baseline indicates improvement. | Baseline (Day 1) to Weeks 2, 4, 6, 8, 10, and 12 | 
| Change From Baseline in Geometric Mean IELT | IELT, the time from vaginal penetration to ejaculation, was measured by a stopwatch and was recorded in the SID. The Logarithm Value of the Geometric Mean of each individual participant's IELT recorded in the SID up to each time point was calculated. The mean and SD of log-transformed geometric mean IELTs were then calculated for each treatment group. An ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate was used for analyses. A positive change from Baseline indicates improvement. | Baseline (Day 1) to Weeks 2, 4, 6, 8, and 10 |