Study to Assess Enobosarm (GTx-024) in Postmenopausal Women With Stress Urinary Incontinence
Condition: Stress Urinary Incontinence
MeSH terms: Urinary Incontinence; Enuresis; Urinary Incontinence, Stress
Intervention: GTx 024; Placebo
Intervention description: Study drug is an opaque, white to off-white, size 5, oval Softgel capsule containing the active ingredient GTx-024.; Placebo study drug is identical in appearance to the GTx-024 study drug and contains polyethylene glycol 400 but not GTx-024.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention 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 (Participant, Investigator)
Enrollment: 491.0
Sex: Female
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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