Efficacy, safety, and tolerability of mirabegron in patients aged ≥65yr with overactive bladder wet: a phase IV, double-blind, randomised, placebo-controlled study (PILLAR)

Abstract

Background: The majority of patients with overactive bladder (OAB) are aged >65yr. There has been no prospectively designed study assessing treatment efficacy with the β3-adrenoreceptor agonist, mirabegron, specifically in this age group.

Objective: A phase IV study comparing flexibly dosed mirabegron versus placebo in elderly patients with OAB and urgency incontinence.

Design, setting, and participants: Community-dwelling patients aged ≥65yr with OAB for ≥3mo.

Intervention: Following a 2-wk placebo run in, patients with one or more incontinence episodes, three or more urgency episodes, and an average of eight or more micturitions/24h were randomised 1:1 to double-blind 25mg/d mirabegron or matched placebo, for 12wk. After week 4 or 8, the dose could be increased to 50mg/d mirabegron/matched placebo based on patient and investigator discretion.

Outcome measurements and statistical analysis: Coprimary endpoints: change from baseline to end of treatment (EOT) in the mean numbers of micturitions/24h and incontinence episodes/24h. Secondary endpoints: change from baseline to EOT in the mean volume voided/micturition, mean number of urgency episodes/24h, and mean number of urgency incontinence episodes/24h. Analysis of covariance (ANCOVA) was used for the mean number of micturitions/24h, mean volume voided/micturition, and mean number of urgency episodes/24h. Stratified rank ANCOVA was used for the mean numbers of incontinence episodes/24h and urgency incontinence episodes/24h.

Results and limitations: Statistically significant improvements were observed for mirabegron versus placebo in change from baseline to EOT in the mean number of micturitions/24h, mean number of incontinence episodes/24h, mean volume voided/micturition, mean number of urgency episodes/24h, and mean number of urgency incontinence episodes/24h. Safety and tolerability were consistent with the known mirabegron safety profile.

Conclusions: Mirabegron efficacy, safety, and tolerability over 12 wk were confirmed in patients aged ≥65yr with OAB and incontinence.

Patient summary: We examined the effect of mirabegron compared with placebo in people aged 65yr or older with overactive bladder and incontinence. Mirabegron improved the symptoms of overactive bladder compared with placebo. Side effects were similar to those already known for mirabegron.

Keywords: Aged; Clinical trial phase IV; Cognition; Lower urinary tract symptoms; Overactive; Urinary bladder.