Reductions in bothersome symptoms of overactive bladder (OAB) demonstrate improvement in clinical trials, but patient perception of meaningfulness of such improvement is lacking. In the 12-week phase 3 EMPOWUR trial, vibegron significantly reduced average daily number of micturitions, urgency episodes, and urge urinary incontinence (UUI) episodes vs placebo (P < 0. 01 each). This analysis assessed meaningfulness of reductions in clinical endpoints observed in EMPOWUR using patient perception of improvement.
An anchor-based approach using Patient Global Impression of Change (PGI-C) applied to phase 2 data allowed predefining phase 3 responder definitions. To confirm in phase 3, median change from baseline at week 12 in average daily number of micturitions, urgency episodes, and UUI episodes was generated for each PGI-C category and pooled across treatments. Based on predefined meaningful responder definitions, percentages of patients achieving ≥ 15% reduction in micturitions (post hoc), ≥ 50% reduction in urgency episodes (predefined), and ≥ 75% (predefined) and ≥ 90% (post hoc) reduction in UUI episodes were determined for patients receiving vibegron or placebo.
Across treatments, for micturitions, urgency episodes, and UUI episodes, median change from baseline to week 12 increased with greater subjective improvement based on PGI-C scores, and median reductions pooled across treatment groups were higher than the responder definitions that patients perceived as improved. Significantly more patients receiving vibegron vs placebo achieved ≥ 15% reduction in micturitions (56.3% vs 44.6%, respectively), ≥ 50% reduction in urgency episodes (39.5% vs 32.8%), ≥ 75% reduction in UUI episodes (49.3% vs 32.8%), and ≥ 90% reduction in UUI episodes (35.2% vs 23.5%) at week 12 (P < 0.05 each).
Significantly more patients treated with vibegron vs placebo in EMPOWUR achieved meaningful reductions in micturitions, urgency episodes, and UUI episodes that were associated with patient-perceived improvement. Results of these analyses support the meaningfulness of reductions in clinical endpoints observed in the 12-week EMPOWUR trial.
ClinicalTrials.gov identifier, NCT03492281.
Advances in therapy. 2021 Dec 18 [Epub ahead of print]
Jeffrey Frankel, David Staskin, Susann Varano, Michael Kennelly, Diane K Newman, Matt T Rosenberg, Rachael A Jankowich, Denise Shortino, Paul N Mudd, Cynthia J Girman
Seattle Urology Research Center, Seattle, WA, USA., Tufts University School of Medicine, Boston, MA, USA., Clinical Research Consulting, Milford, CT, USA., Carolinas Medical Center, Charlotte, NC, USA., Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Mid-Michigan Health Centers, Jackson, MI, USA., Urovant Sciences, Irvine, CA, USA., CERobs Consulting, LLC, 2612 Lumina Avenue North, Wrightsville Beach, Chapel Hill, NC, 28480, USA. .