Stress Urinary Incontinence
Conditions
Brief 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.
Interventions
DRUGGTx 024
Study drug is an opaque, white to off-white, size 5, oval Softgel capsule containing the active ingredient GTx-024.
DRUGPlacebo
Placebo study drug is identical in appearance to the GTx-024 study drug and contains polyethylene glycol 400 but not GTx-024.
Sponsors
GTx
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
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.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a ≥ 50% Reduction From Baseline in the Mean Number of Stress Incontinence Episodes Per Day at Week 12 | 12 Weeks | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1 mg GTx-024 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.
GTx 024: Study drug is an opaque, white to off-white, size 5, oval Softgel capsule containing the active ingredient GTx-024. | 163 |
| 3 mg GTx-024 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.
GTx 024: Study drug is an opaque, white to off-white, size 5, oval Softgel capsule containing the active ingredient GTx-024. | 163 |
| Matching Placebo 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.
Placebo: Placebo study drug is identical in appearance to the GTx-024 study drug and contains polyethylene glycol 400 but not GTx-024. | 165 |
| Total | 491 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 8 | 4 |
| Overall Study | Lack of Efficacy | 0 | 0 | 1 |
| Overall Study | noncompliance with study drug | 2 | 1 | 1 |
| Overall Study | not reported | 15 | 21 | 19 |
| Overall Study | sponsor decision | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | Matching Placebo | 1 mg GTx-024 | 3 mg GTx-024 | Total |
|---|---|---|---|---|
| Age, Continuous | 58 years | 60 years | 59 years | 59 years |
| Baseline number of stress incontinence episodes per day | 4.459 episodes per day | 4.588 episodes per day | 4.329 episodes per day | 4.4 episodes per day |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 13 Participants | 10 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 150 Participants | 149 Participants | 152 Participants | 451 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 3 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 25 Participants | 20 Participants | 57 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) White | 150 Participants | 131 Participants | 139 Participants | 420 Participants |
| Sex: Female, Male Female | 165 Participants | 163 Participants | 163 Participants | 491 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 163 | 0 / 163 | 0 / 165 |
| other Total, other adverse events | 105 / 163 | 104 / 163 | 96 / 165 |
| serious Total, serious adverse events | 3 / 163 | 2 / 163 | 4 / 165 |
Outcome results
Primary
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
Time frame: 12 Weeks
Population: full analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1 mg GTx-024 | Number of Participants With a ≥ 50% Reduction From Baseline in the Mean Number of Stress Incontinence Episodes Per Day at Week 12 | 94 Participants |
| 3 mg GTx-024 | Number of Participants With a ≥ 50% Reduction From Baseline in the Mean Number of Stress Incontinence Episodes Per Day at Week 12 | 96 Participants |
| Matching Placebo | Number of Participants With a ≥ 50% Reduction From Baseline in the Mean Number of Stress Incontinence Episodes Per Day at Week 12 | 87 Participants |