Study to Assess Enobosarm (GTx-024) in Postmenopausal Women With Stress Urinary Incontinence

Study Overview
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Brief Summary
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GTx-024 is an orally bioavailable and tissue-selective nonsteroidal selective androgen receptor modulator (SARM) that has demonstrated androgenic and anabolic activity and is currently being evaluated as a potential treatment for stress urinary incontinence (SUI) in postmenopausal women. Urinary incontinence and pelvic floor disorders are major health problems for women, especially as they age. Pelvic floor muscle relaxation has been found to correlate with lower urinary tract symptoms including SUI. Muscles of the pelvic floor and lower urinary tract are crucial for supporting the pelvic organs and micturition; however, damage to the muscles or lack of hormonal stimulation are thought to contribute to pelvic organ prolapse and urinary incontinence. Although anabolic steroids may increase muscle mass and strength, lack of oral bioavailability and known potential risks have limited their use. Nonsteroidal SARMs have potential to achieve benefits of anabolic steroid therapy (improved muscle mass, cholesterol/triglyceride levels, glucose metabolism, and bone density) with fewer adverse effects, such as hirsutism and acne, in women. Both nonclinical and clinical data suggest that SARMs may provide a new therapeutic option for pelvic floor and lower urinary tract disorders, as both testosterone and its more potent metabolite, dihydrotestosterone, have anabolic effects on muscle.

Official Title
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Double-Blind, Placebo-Controlled, Parallel Design, Phase 2 Study to Assess Clinical Activity and Safety of Enobosarm (GTx-024) in Postmenopausal Women With Stress Urinary Incontinence

Conditions
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Stress Urinary Incontinence

Intervention / Treatment
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* Drug: GTx 024
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: SUI symptoms of at least 6 months duration Predominant SUI as determined at the Screening Visit using the Medical, Epidemiological, and Social Aspects of Aging (MESA) urinary questionnaire. 24-Hour pad weight > 3 g during the screening period A minimum of 1 and no more than 15 SUI episodes on any single day AND no fewer than 9 total SUI episodes over 3 days during the screening period Positive bladder stress test conducted during the Screening Visit Key Exclusion Criteria: History of pelvic radiation treatment History of urethral diverticula History of urethral sling or anterior prolapse repair Treatment with urethral bulking agents and/or other SUI procedure or surgery within the 6 months prior to the Screening Visit Known vesicoureteral reflux, vaginal prolapse beyond the introitus, or other significant pelvic floor abnormalities Urinary incontinence of neurogenic etiology Morbidly obese (defined as 100 pounds over ideal body weight, or body mass index 40 or greater) Chronic hepatitis Hepatic cirrhosis Evidence of active infection with hepatitis B or hepatitis C History of human immunodeficiency virus (HIV) infection Subjects with a history of breast or endometrial cancer

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

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: Parallel Assignment
Interventional Model Description: Double-blind, placebo-controlled, parallel design, randomized, multicenter, Phase 2 study consisting of the following periods: screening period, treatment period, and follow-up period.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1 mg GTx-024<br>Study drug will be provided as softgel capsules in blister packaging, labeled and designed to protect study blinding. All subjects will take 2 softgel capsules orally, once daily. | Drug: GTx 024<br>* Study drug is an opaque, white to off-white, size 5, oval Softgel capsule containing the active ingredient GTx-024.<br>* Other names: Enobosarm;|
| Active Comparator: 3 mg GTx-024<br>Study drug will be provided as softgel capsules in blister packaging, labeled and designed to protect study blinding. All subjects will take 2 softgel capsules orally, once daily. | Drug: GTx 024<br>* Study drug is an opaque, white to off-white, size 5, oval Softgel capsule containing the active ingredient GTx-024.<br>* Other names: Enobosarm;|
| Placebo Comparator: matching placebo<br>Study drug will be provided as softgel capsules in blister packaging, labeled and designed to protect study blinding. All subjects will take 2 softgel capsules orally, once daily. | Drug: Placebo<br>* Placebo study drug is identical in appearance to the GTx-024 study drug and contains polyethylene glycol 400 but not GTx-024.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a ≥ 50% Reduction From Baseline in the Mean Number of Stress Incontinence Episodes Per Day at Week 12 | Mean number of subject-reported stress incontinence episodes per day through a responder analysis, where a responder is defined as having a ≥ 50% reduction at the end of treatment (Week 12) compared to baseline in the number of stress incontinence episodes | 12 Weeks |