Safety and Tolerability Results from the PILLAR Study: A Phase IV, Double-Blind, Randomized, Placebo-Controlled Study of Mirabegron in Patients ≥ 65 years with Overactive Bladder-Wet.

In older patients with overactive bladder (OAB), mirabegron, a β3-adrenoreceptor agonist, represents an alternative treatment that may have a favorable risk-benefit profile.

Our objective was to further examine the safety and tolerability of mirabegron versus placebo treatment in patients aged ≥ 65 years with OAB-wet.

We conducted a 12-week, double-blind, randomized, placebo-controlled phase IV study to compare mirabegron with placebo. Community-dwelling patients aged ≥ 65 years with OAB-wet (one or more incontinence episode and three or more urgency episodes, and an average of eight or more micturitions/24 h over a 3-day diary) were randomized to receive placebo or mirabegron 25 mg/day (optional dose escalation to 50 mg/day at week 4 or 8). Safety analyses were performed for adverse events (AEs) and vital signs on all randomized patients who received one or more dose of study drug.

Treatment-emergent AEs (TEAEs), the majority mild or moderate in severity, were reported in 39.4% of placebo patients and 44.2 and 49.8% of those who received mirabegron 25 mg or 50 mg, respectively. The most common TEAEs in mirabegron-treated patients were urinary tract infection, headache, and diarrhea. The incidence of TEAEs was slightly higher in mirabegron patients aged ≥ 75 years than in those aged < 75 years. There were no clinically meaningful differences in changes in vital signs from baseline to end of treatment for any treatment group, and no differences were observed between mirabegron and placebo treatment groups. TEAEs tended to occur early post exposure and were not dose related.

Mirabegron treatment was well-tolerated in older adults with OAB-wet. Safety and tolerability were consistent with the known mirabegron safety profile.

This study is registered at ClinicalTrials.gov: NCT02216214.

Drugs & aging. 2020 Jul 28 [Epub ahead of print]

Sender Herschorn, David Staskin, Carol R Schermer, Rita M Kristy, Adrian Wagg

Department of Surgery/Urology, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, MG408, Toronto, Ontario, M4N 3M5, Canada. ., Division of Urology, St Elizabeth's Medical Center, 736 Cambridge Street, Brighton, MA, USA., Astellas Pharma Global Development, Inc., 1 Astellas Way, Northbrook, IL, 60062, USA., Department of Medicine, University of Alberta, 1-198 Clinical Sciences Building, 11350 83 Avenue, Edmonton, AB, Canada.