Efficacy and safety of mirabegron vs. placebo add-on therapy in men with overactive bladder symptoms receiving tamsulosin for underlying lower urinary tract symptoms (PLUS)
Professor Eric Chung, Steven Kaplan (1), Sender Herschorn (2), Kevin McVary (3), David Staskin (4), Christopher Chapple (5), Steve Foley (6), Javier Cambronero Santos (7), Rita M. Kristy (8), Nurul Choudhury (9), John Hairston (8), Carol Schermer (8)
(1) Department of Urology, Icahn School of Medicine at Mount Sinai, New York City, USA, (2) Department of Surgery/Urology, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Canada, (3) Department of Urology, Stritch School of Medicine, Loyola University Medical Center, Maywood, USA, (4) Department of Urology, St Elizabeth's Medical Center, Brighton, USA, (5) Department of Urology, Royal Hallamshire Hospital, Sheffield, UK, (6) Department of Urology, Royal Berkshire Hospital, Reading, UK, (7) Department of Urology, Infanta Leonor Hospital, Madrid, Spain, (8) Astellas Pharma Global Development Inc., Northbrook, USA, (9) Astellas Pharma Europe Ltd., Chertsey, UK
The objective was to study the efficacy and safety of mirabegron vs. placebo for treating storage symptoms suggestive of overactive bladder (OAB) in men concurrently receiving tamsulosin for lower urinary tract symptoms (LUTS) associated with underlying benign prostatic hyperplasia (BPH).
This 12-week, phase IV, randomized, double-blind, multi-centre (North America/Europe) study enrolled men (≥40 years) who had received tamsulosin for ≥2 months, had a prostate specific antigen level of <10 ng/mL, and had experienced ≥8 micturitions/day and ≥2 urgency episodes/day. After a 4-week tamsulosin run-in period, patients were randomized to either mirabegron 25 mg or placebo. At 4 weeks, all patients were titrated to mirabegron 50 mg or placebo equivalent for 8 more weeks. Primary endpoint was change from Baseline to week 12/end of treatment in mean number of micturitions/24 h. Changes in mean volume voided (MVV)/micturition, urgency episodes/day, total urgency and frequency score (TUFS), and total International Prostate Symptom Score (IPSS) were analysed. Safety assessments included treatment-emergent adverse events (TEAEs) and changes in post-void residual (PVR) volume and maximum urinary flow (Qmax). A total of 544 patients provided 80% power to detect a reduction of 0.65 in the mean number of micturitions/24 h for mirabegron over placebo (alpha level: 0.05, assumed standard deviation: 2.7). Of 706 men included in the study, mean age was 65.0 years (399 [56.5%]) were ≥65 years).
The adjusted mean change in micturitions/24 h for tamsulosin+mirabegron was statistically superior to tamsulosin+placebo (Table). Statistically superior results were also obtained for tamsulosin+mirabegron in MVV/micturition, urgency episodes/day, and TUFS (no significant difference seen in total IPSS). TEAE rates were higher with tamsulosin+placebo, although drug-related TEAE rates were higher with tamsulosin+mirabegron. Serious TEAE rates were similar in both groups. One (0.3%) tamsulosin+placebo and six (1.7%) tamsulosin+mirabegron patients experienced urinary retention. Changes in mean PVR volume and Qmax were not clinically meaningful.
Among men receiving tamsulosin for LUTS and associated BPH, the addition of mirabegron was superior to placebo in mean number of micturitions/24 h in patients with storage 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 mirabegron add-on therapy in male presenting with LUTS.This study was sponsored by Astellas.