COURAGE: Vibegron for Persistent Overactive Bladder Symptoms in Men Treated for BPH
COURAGE was a multicenter, double-blind, placebo-controlled phase 3 trial in 1,105 men aged 45 years or older with persistent overactive bladder (OAB) symptoms despite a stable α-blocker, with or without a 5α-reductase inhibitor, for BPH, comparing added vibegron 75 mg daily with placebo. At 12 weeks vibegron reduced daily micturitions by 0.74 more than placebo (95% CI 0.46–1.02) and urgency episodes by 0.95 more (95% CI 0.54–1.37), meeting both coprimary endpoints.[1]
- Design and population
- Multicenter, double-blind, placebo-controlled randomized superiority trial. 1,105 men aged 45 years or older with at least 8 micturitions and 3 urgency episodes daily despite a stable α-blocker, with or without a 5α-reductase inhibitor, for BPH.
- Arms
- Vibegron 75 mg once daily added to an α-blocker with or without a 5α-reductase inhibitor versus matched placebo added to an α-blocker with or without a 5α-reductase inhibitor
- Report and follow-up
- 2024 · 12 weeks for the coprimary endpoints; 24-week double-blind treatment period
| Endpoint | Results | Effect | Finding |
|---|---|---|---|
| Week 12 least-squares mean change from baseline in mean daily micturitions (per day); least-squares mean difference, vibegron minus placebo | −2.04 vs −1.30 | difference -0.74; CI -1.02–-0.46; P <0.0001 | Met |
| Week 12 least-squares mean change from baseline in mean daily urgency episodes (per day); least-squares mean difference, vibegron minus placebo | −2.88 vs −1.93 | difference -0.95; CI -1.37–-0.54; P <0.0001 | Met |
| Week 12 least-squares mean change from baseline in nightly nocturia episodes; least-squares mean difference, vibegron minus placebo | −0.88 vs −0.66 | difference -0.22; CI -0.36–-0.09; P 0.002 | Met |
| Week 12 least-squares mean change from baseline in daily urge urinary incontinence episodes; least-squares mean difference, vibegron minus placebo | −2.19 vs −1.39 | difference -0.8; CI -1.33–-0.27; P 0.003 | Met |
| Week 12 least-squares mean change from baseline in IPSS storage score; least-squares mean difference, vibegron minus placebo | −3.0 vs −2.1 | difference -0.9; CI -1.2–-0.6; P <0.0001 | Met |
| Week 12 least-squares mean change from baseline in volume voided per micturition (mL); least-squares mean difference, vibegron minus placebo | +25.63 mL vs +10.56 mL | difference 15.07; CI 9.13–21.02; P <0.0001 | Met |
Harms: Any treatment-emergent adverse event: 249/553 (45.0%) vs 215/551 (39.0%); Serious treatment-emergent adverse events: 24/553 (4.3%) vs 16/551 (2.9%); Adverse events leading to discontinuation: 16/553 (2.9%) vs 15/551 (2.7%)
Design
Men had at least 8 micturitions and 3 urgency episodes a day on a bladder diary for at least 2 months, an IPSS of at least 8 and at least 2 nocturia episodes a night. The α-blocker had been started at least 3 months and any 5α-reductase inhibitor at least 6 months before screening. Exclusions were a 24-hour urine volume above 3,000 mL, nocturnal polyuria, Qmax below 5 mL/s, prior retention, prior prostate surgery, recent botulinum toxin, resiniferatoxin or capsaicin, and sacral or tibial neuromodulation. Obstruction and detrusor function were not assessed for entry, but a postvoid residual under 100 mL was required at baseline.[1][2]
After screening of up to 5 weeks and a 2-week single-blind placebo run-in, men were randomized 1:1 centrally to vibegron or matched placebo for 24 weeks, stratified by baseline micturitions (12 or fewer versus more than 12), 5α-reductase inhibitor use and presence of incontinence. BPH medication was not changed during the run-in.[1]
The coprimary endpoints were the week 12 change from baseline in mean daily micturitions and urgency episodes on a 3-day diary. Nocturia, urge incontinence episodes, IPSS storage score and volume voided per micturition were tested sequentially after both coprimary endpoints. Enrollment of about 544 men per arm gave about 94% and 90% power to detect differences of 0.46 micturitions and 0.60 urgency episodes a day. Efficacy was analyzed in a full analysis set of 1,080 men (vibegron 538, placebo 542) with a mixed model for repeated measures; the responder analysis was exploratory and unadjusted for multiplicity.[1]
Results
At week 12, daily micturitions fell by 2.04 with vibegron and 1.30 with placebo (difference −0.74; 95% CI −1.02 to −0.46; P < 0.0001), and daily urgency episodes fell by 2.88 and 1.93 (difference −0.95; 95% CI −1.37 to −0.54; P < 0.0001). Baseline median daily micturitions were 11.3 with vibegron and 11.7 with placebo.[1]
All four secondary endpoints improved at week 12. Nocturia fell by 0.88 versus 0.66 episodes a night (difference −0.22; 95% CI −0.36 to −0.09; P = 0.002). Among 297 men with baseline incontinence, urge incontinence episodes fell by 2.19 versus 1.39 a day (difference −0.80; 95% CI −1.33 to −0.27; P = 0.003). The IPSS storage score fell by 3.0 versus 2.1 points (difference −0.9; 95% CI −1.2 to −0.6; P < 0.0001), and volume voided per micturition rose by 25.63 versus 10.56 mL (difference 15.07 mL; 95% CI 9.13–21.02; P < 0.0001).[1]
In a post hoc responder analysis at week 12, 33.3% of men on vibegron versus 20.5% on placebo reached 8 or fewer daily micturitions (P < 0.0001), 34.6% versus 26.8% reached 1 or fewer nocturia episodes a night (P = 0.0036), and, among the 297 men with baseline incontinence, 65.8% versus 53.0% reached 1 or fewer urge incontinence episodes a day (P = 0.0267).[3]
Surgery and treatment delivery
Vibegron was added to unchanged BPH medication. Of 1,105 men randomized, 1,104 received at least one dose and 965 (87.3%) completed the 24-week treatment period. A 5α-reductase inhibitor was taken with the α-blocker by 126 of 538 men (23.4%) in the vibegron arm and 123 of 542 (22.7%) in the placebo arm, and prior anticholinergic use was 14.3% and 14.9%.[1]
Adverse events
Any treatment-emergent adverse event occurred in 249 of 553 men (45.0%) given vibegron and 215 of 551 (39.0%) given placebo; serious events occurred in 24 (4.3%) and 16 (2.9%), none judged treatment related, and discontinuation for an adverse event in 16 (2.9%) and 15 (2.7%). Hypertension was reported in 50 (9.0%) and 46 (8.3%), urinary tract infection in 14 (2.5%) and 12 (2.2%), and neoplasms in 6 (1.1%) and 1 (0.2%), all diagnosed within 80 days of starting treatment and none judged treatment related. No deaths occurred.[1]
Urinary retention requiring catheterization occurred in 5 of 553 men (0.9%) on vibegron and 3 of 551 (0.5%) on placebo.[1] In the bladder-function report, which counted 4 of 551 (0.7%) retention events on placebo, 8 of the 9 retention cases had at least one baseline risk factor (Qmax below 12 mL/s, prostate volume of at least 40 mL or PSA of at least 1.4 µg/L), and 78.8% of the vibegron arm and 78.4% of the placebo arm had at least one. At week 24, a residual of 100 to under 200 mL was recorded in 24 of 493 men (4.9%) on vibegron and 13 of 482 (2.7%) on placebo, and 200 to under 300 mL in 3 (0.6%) and none; no one had 300 mL or more. The week 24 difference in postvoid residual change was 7.17 mL (95% CI 3.12–11.22) and in uroflowmetry Qmax 0.05 mL/s (95% CI −0.95 to 1.05).[2]
In a urodynamics substudy of 43 evaluable men (vibegron 21, placebo 22), the week 12 difference in change in Qmax was 2.75 mL/s (95% CI 0.16–5.34), above the −3 mL/s noninferiority margin, and in detrusor pressure at Qmax 2.86 cmH2O (95% CI −13.52 to 19.25); the post hoc bootstrap upper limit of 14.61 cmH2O was below the 15 cmH2O margin.[2]
Limitations
Entry depended on a BPH diagnosis and symptom scores without formal assessment of obstruction or detrusor function, so the relation of the OAB symptoms to outlet obstruction is not defined, and every participant was already taking BPH medication. Men with prior retention, Qmax below 5 mL/s or postvoid residual of 100 mL or more were not enrolled. The urodynamics substudy was small and its detrusor-pressure interval crossed the noninferiority margin before the bootstrap estimate. Three authors were employees of the manufacturer, Sumitomo Pharma America, at the time of the study.[1][2]
In conversation
Earlier randomized add-on trials of a β3 agonist in men were limited to tamsulosin or silodosin background therapy, and one excluded men taking a 5α-reductase inhibitor; COURAGE allowed any α-blocker with or without a 5α-reductase inhibitor and required persistent OAB symptoms defined by diary counts.[1]
Guidelines and approvals
- AUA (BPH guideline 2026, Part II: medical management), statement 28. In patients with moderate to severe predominant storage LUTS, clinicians may offer β3 agonists alone or in combination with an α-blocker . The supporting text cites COURAGE for improved urgency, frequency and nocturia with vibegron in men on an α-blocker or 5α-reductase inhibitor.[4]
- EAU (Non-neurogenic Male LUTS, March 2026 update), section 5.2.7.c. Use combination treatment of an α1-blocker with a β3 agonist in patients with persistent storage LUTS after α1-blocker monotherapy . The text cites COURAGE for the week 12 improvement in micturitions and urgency episodes and for similar adverse-event rates with vibegron and placebo.[5]
- FDA (December 18, 2024). Supplement to NDA 213006 approved vibegron (Gemtesa) for OAB with urge urinary incontinence, urgency and frequency in adult males on pharmacological therapy for BPH.[6]
Report history
| Published | Report | Cutoff | Headline results | Citation |
|---|---|---|---|---|
| 2024-05-06 | Primary report · primary | — | Week 12 least-squares mean change from baseline in mean daily micturitions (per day); least-squares mean difference, vibegron minus placebo: −2.04 vs −1.30; difference -0.74; CI -1.02–-0.46; P <0.0001 Met Week 12 least-squares mean change from baseline in mean daily urgency episodes (per day); least-squares mean difference, vibegron minus placebo: −2.88 vs −1.93; difference -0.95; CI -1.37–-0.54; P <0.0001 Met Week 12 least-squares mean change from baseline in nightly nocturia episodes; least-squares mean difference, vibegron minus placebo: −0.88 vs −0.66; difference -0.22; CI -0.36–-0.09; P 0.002 Met Week 12 least-squares mean change from baseline in daily urge urinary incontinence episodes; least-squares mean difference, vibegron minus placebo: −2.19 vs −1.39; difference -0.8; CI -1.33–-0.27; P 0.003 Met Week 12 least-squares mean change from baseline in IPSS storage score; least-squares mean difference, vibegron minus placebo: −3.0 vs −2.1; difference -0.9; CI -1.2–-0.6; P <0.0001 Met Week 12 least-squares mean change from baseline in volume voided per micturition (mL); least-squares mean difference, vibegron minus placebo: +25.63 mL vs +10.56 mL; difference 15.07; CI 9.13–21.02; P <0.0001 Met | Staskin D, Owens-Grillo J, Thomas E, et al. Efficacy and safety of vibegron for persistent symptoms of overactive bladder in men being pharmacologically treated for benign prostatic hyperplasia: results from the phase 3 randomized controlled COURAGE trial. *J Urol.* 2024;212(2):256-266. doi:10.1097/JU.0000000000003999 DOI |
| 2025-09-01 | Responder analysis · post-hoc | — | Week 12 proportion with 8 or fewer daily micturitions: 33.3% vs 20.5%; P <0.0001 Week 12 proportion with 1 or fewer nightly nocturia episodes: 34.6% vs 26.8%; P 0.0036 Week 12 proportion with 1 or fewer daily urge urinary incontinence episodes among men with incontinence at baseline (full analysis set for incontinence: vibegron 146, placebo 151): 65.8% vs 53.0%; P 0.0267 | Peters KM, Owens-Grillo J, Thomas E, et al. Clinically meaningful improvements with vibegron in men with overactive bladder and benign prostatic hyperplasia: a responder analysis of the phase 3 COURAGE trial. *Urology.* 2025;206:150-156. doi:10.1016/j.urology.2025.08.051 DOI |
| 2025-12-09 | Bladder function and urodynamics · secondary | — | Least-squares mean difference in change from baseline in postvoid residual volume at week 12 (mL), vibegron minus placebo: Safety analysis set (553 vibegron, 551 placebo); baseline postvoid residual under 100 mL was required.; difference 3.04; CI -1.28–7.36 Least-squares mean difference in change from baseline in postvoid residual volume at week 24 (mL), vibegron minus placebo: Safety analysis set.; difference 7.17; CI 3.12–11.22 Least-squares mean difference in change from baseline in uroflowmetry Qmax at week 24 (mL/s), vibegron minus placebo: Safety analysis set.; difference 0.05; CI -0.95–1.05 Mean (SD) change from baseline in IPSS total score at week 24: −7.3 (7.0) vs −5.7 (7.1); — Least-squares mean difference in change from baseline in urodynamic Qmax at week 12 (mL/s), vibegron minus placebo: Urodynamics evaluable set of 43 (vibegron 21, placebo 22) from 95 men randomized to the substudy. Noninferiority margin −3 mL/s; the authors report noninferiority confirmed.; difference 2.75; CI 0.16–5.34 Least-squares mean difference in change from baseline in detrusor pressure at Qmax at week 12 (cmH2O), vibegron minus placebo: Urodynamics evaluable set of 43. Noninferiority margin 15 cmH2O; the conventional interval crossed the margin and a post hoc bootstrap one-sided 95% interval (upper limit 14.61) did not.; difference 2.86; CI -13.52–19.25 | Rovner ES, Owens-Grillo J, Thomas E, et al. Bladder function and safety of vibegron in men with overactive bladder receiving treatment for benign prostatic hyperplasia: outcomes from the phase 3 randomized controlled COURAGE trial. *Neurourol Urodyn.* 2026;45(2):299-304. doi:10.1002/nau.70199 DOI |
References
1. Staskin D, Owens-Grillo J, Thomas E, et al. "Efficacy and Safety of Vibegron for Persistent Symptoms of Overactive Bladder in Men Being Pharmacologically Treated for Benign Prostatic Hyperplasia: Results From the Phase 3 Randomized Controlled COURAGE Trial." J Urol. 2024;212(2):256-266. doi:10.1097/JU.0000000000003999
2. Rovner ES, Owens-Grillo J, Thomas E, et al. "Bladder Function and Safety of Vibegron in Men With Overactive Bladder Receiving Treatment for Benign Prostatic Hyperplasia: Outcomes From the Phase 3 Randomized Controlled COURAGE Trial." Neurourol Urodyn. 2026;45(2):299-304. doi:10.1002/nau.70199
3. Peters KM, Owens-Grillo J, Thomas E, et al. "Clinically Meaningful Improvements With Vibegron in Men With Overactive Bladder and Benign Prostatic Hyperplasia: A Responder Analysis of the Phase 3 COURAGE Trial." Urology. 2025;206:150-156. doi:10.1016/j.urology.2025.08.051
4. Goueli R, Badlani GH, Welliver C, et al. "Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia: AUA Guideline (2026) Part II: Medical Management." J Urol. 2026;216(2):152-160. doi:10.1097/JU.0000000000005098
5. Cornu JN, Elterman D, Hashim H, et al. EAU Guidelines on Management of Non-neurogenic Male Lower Urinary Tract Symptoms (LUTS). Arnhem: EAU Guidelines Office; March 2026 update. Section 5.2.7.c, p. 34.
6. U.S. Food and Drug Administration. Supplement approval letter, NDA 213006/S-011 (Gemtesa, vibegron). December 18, 2024.