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

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

Abstract

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

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

Methods: 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.

Results: 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.

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

Trial registration: This study is registered at ClinicalTrials.gov: NCT02216214.

Conflict of interest statement

Sender Herschorn has received grants from Astellas, Urovant, and Allergan and personal fees from Astellas and Pfizer. David Staskin has received grants and personal fees for services as an investigator, consultant, and speaker for Astellas. Carol R. Schermer and Rita M. Kristy are employees of Astellas Pharma Global Development, Inc. Adrian Wagg has received grants, personal fees, and other non-financial support from Astellas, Essity, Pfizer, and Pierre Fabre.

Figures

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Fig. 1
Study flow chart

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