Efficacy and safety of mirabegron vs. placebo add-on therapy in men with overactive bladder symptoms receiving tamsulosin for underlying benign prostatic hyperplasia (PLUS)

INTRODUCTION AND OBJECTIVES: In men, overactive bladder (OAB) symptoms commonly overlap with those of benign prostatic hyperplasia (BPH), but limited data are available on the use of OAB medications in these patients. The objective was to study the efficacy and safety of mirabegron (MIRA) vs. placebo (PL) for treating OAB symptoms in men concurrently receiving tamsulosin (TAM) for lower urinary tract symptoms (LUTS) due to underlying BPH. METHODS: This 12-wk, phase IV, randomized, double-blind, multi-center (North America/Europe) study enrolled men aged >40 yr who had received TAM for >2 mo. After a 4-wk TAM run-in period, patients were randomized to either MIRA 25 mg or PL. At 4 wk, all patients were titrated to MIRA 50 mg or PL equivalent for 8 more wk. Primary endpoint was change from Baseline (BL) to wk 12/end of treatment (EoT) in mean number of micturitions/24 h. Changes from BL in mean volume voided (MVV)/micturition, urgency episodes/day, total urgency and frequency score (TUFS), and International Prostate Symptom Score (IPSS) total score were analyzed. Safety assessments included treatment-emergent adverse events (TEAEs) and changes in post-void residual (PVR) volume and maximum urinary flow (Qmax). RESULTS: Of 676 men, mean age was 64.9 yr (380 =56.2%] were >65 yr). The adjusted mean change from BL to EoT in micturitions/24 h for TAM+MIRA was statistically superior to TAM+PL (Table). Statistically superior results were also obtained for TAM+MIRA in MVV/micturition, urgency episodes/day, and TUFS (no significant difference was seen in IPSS total score). TEAE rates were higher with TAM+PL, although drug-related TEAE rates were higher with TAM+MIRA. Serious TEAE rates were similar in both groups. One (0.3%) TAM+PL and six (1.7%) TAM+MIRA patients experienced urinary retention (two TAM+MIRA patients required catheterization). Changes in mean PVR volume and Qmax were not clinically meaningful. CONCLUSIONS: Among men receiving TAM for LUTS due to BPH, the addition of MIRA was superior to PL in mean number of micturitions/24 h in patients with OAB symptoms. Similar findings were observed for MVV/micturition, urgency episodes/day, and TUFS. There were no unexpected safety concerns. These results underscore the potential utility of MIRA add-on therapy in men with BPH.