Hypothesis / aims of study
Overactive bladder (OAB) syndrome prevalence increases with age. Vibegron is a β3-adrenergic agonist approved for adults with OAB. In the phase 3 EMPOWUR extension trial [1], once-daily vibegron 75 mg showed long-term safety and efficacy in patients with OAB, consistent with results of the 12-week study [2]. These post hoc analyses of the extension trial assessed safety and efficacy in patients ≥65 years old.
Study design, materials and methods
Patients completing the EMPOWUR trial could enter the 40-week extension trial (NCT03583372). Patients previously receiving vibegron or tolterodine 4 mg extended release continued active treatment; patients previously receiving placebo were randomly assigned 1:1 to vibegron or tolterodine. The primary outcome was safety, assessed by adverse events (AEs). Key efficacy endpoints were change from EMPOWUR baseline at week 52 in average daily micturitions, urgency urinary incontinence (UUI) episodes, and urgency episodes. Outcomes were assessed in patients ≥65 years old. No formal sample size calculation was performed; it was determined that rolling 500 patients over from the EMPOWUR trial was sufficient to characterize the long-term safety profile of vibegron. The study was approved by an institutional review board, research ethics board, or independent ethics committee prior to study initiation; all patients provided written informed consent.
Results
Of 505 patients receiving ≥1 dose of study drug in the extension (n=273, vibegron; n=232, tolterodine), 235 patients (46.5%) were ≥65 years old, and 60 patients (11.9%) were ≥75 years old. Of the patients ≥65 years old, 71.1% were women, and 75.7% had OAB wet (ie, with incontinence). Of the patients ≥75 years old, 55.0% were women, and 68.3% had OAB wet. After 40‒52 weeks of treatment, the rate of treatment-related AEs was similar between vibegron (33.3%) and tolterodine (25.5%) (Table 1). The most commonly occurring AEs were hypertension (10.9% with vibegron vs 9.4% with tolterodine), urinary tract infection (7.8% vs 12.3%, respectively), and headache (7.0% vs 4.7%, respectively). Patients who received 52 weeks of active treatment showed improvement in least squares mean change from baseline at week 52 in average daily number of micturitions (vibegron, −2.3; tolterodine, −1.7), UUI episodes (−1.8; −1.2, respectively), and urgency episodes (−3.3; −2.4, respectively) (Table 2). Safety and efficacy outcomes were generally similar in patients ≥75 years old.
Interpretation of results
In this subgroup analysis of the EMPOWUR extension trial, once-daily vibegron 75 mg was associated with sustained reductions from baseline in micturitions, UUI episodes, and urgency episodes and was safe in older adults (≥65 years) with OAB.