Sender Herschorn1, Kevin T McVary2, Javier Cambronero Santos2, Steve Foley2, Rita M Kristy2, Nurul Choudhury2, John Hairston2, Steven A Kaplan2. 1. Department of Surgery/Urology, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Urology, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL; Department of Urology, Infanta Leonor Hospital, Madrid, Spain; Department of Urology, Royal Berkshire Hospital, Reading, United Kingdom; Astellas Pharma Global Development Inc., Northbrook, IL; Astellas Pharma Europe Ltd., Chertsey, United Kingdom; Department of Urology, Icahn School of Medicine at Mount Sinai, New York City, NY. Electronic address: Sender.Herschorn@sunnybrook.ca. 2. Department of Surgery/Urology, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Urology, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL; Department of Urology, Infanta Leonor Hospital, Madrid, Spain; Department of Urology, Royal Berkshire Hospital, Reading, United Kingdom; Astellas Pharma Global Development Inc., Northbrook, IL; Astellas Pharma Europe Ltd., Chertsey, United Kingdom; Department of Urology, Icahn School of Medicine at Mount Sinai, New York City, NY.
Abstract
OBJECTIVE: To analyze the safety of mirabegron add-on therapy in men with overactive bladder symptoms concurrently receiving tamsulosin for lower urinary tract symptoms associated with benign prostatic hyperplasia. METHODS: The Phase 4 PLUS study comprised a 4-week run-in period (tamsulosin [0.4 mg]) and a 12-week randomized treatment period (add-on treatment: mirabegron [25 mg] or placebo). Doses were increased to mirabegron 50 mg or matched placebo after 4 weeks. Safety assessments: treatment-emergent adverse events (TEAEs), vital signs, 12-lead electrocardiograms, and changes in postvoid residual volume and maximum urinary flow (Qmax). RESULTS: The safety analysis set included 352 tamsulosin plus mirabegron (TAM + MIRA) and 354 tamsulosin plus placebo (TAM + PL) patients. The frequency of overall TEAEs was higher with TAM + PL, although a higher incidence of drug-related TEAEs was observed with TAM + MIRA. Most TEAEs were mild or moderate in severity. Drug-related serious TEAEs were reported for 3 patients (2 TAM + MIRA patients: acute myocardial infarction with cerebral infarction and angina pectoris, 1 TAM + PL patient: lacunar stroke). Hypertension, headache, and nasopharyngitis were the most common TEAEs. Special interest TEAEs were infrequently reported. The most common was urinary retention and 2 TAM + MIRA patients required catheterization (neither led to discontinuation). No major changes in blood pressure or pulse rate were noted and similar electrocardiogram parameters were observed for both groups. Changes in mean postvoid residual volume and Qmax were not clinically meaningful. CONCLUSION: No unexpected safety concerns were noted in men receiving tamsulosin for lower urinary tract symptoms associated with benign prostatic hyperplasia who subsequently received mirabegron add-on therapy.
OBJECTIVE: To analyze the safety of mirabegron add-on therapy in men with overactive bladder symptoms concurrently receiving tamsulosin for lower urinary tract symptoms associated with benign prostatic hyperplasia. METHODS: The Phase 4 PLUS study comprised a 4-week run-in period (tamsulosin [0.4 mg]) and a 12-week randomized treatment period (add-on treatment: mirabegron [25 mg] or placebo). Doses were increased to mirabegron 50 mg or matched placebo after 4 weeks. Safety assessments: treatment-emergent adverse events (TEAEs), vital signs, 12-lead electrocardiograms, and changes in postvoid residual volume and maximum urinary flow (Qmax). RESULTS: The safety analysis set included 352 tamsulosin plus mirabegron (TAM + MIRA) and 354 tamsulosin plus placebo (TAM + PL) patients. The frequency of overall TEAEs was higher with TAM + PL, although a higher incidence of drug-related TEAEs was observed with TAM + MIRA. Most TEAEs were mild or moderate in severity. Drug-related serious TEAEs were reported for 3 patients (2 TAM + MIRA patients: acute myocardial infarction with cerebral infarction and angina pectoris, 1 TAM + PL patient: lacunar stroke). Hypertension, headache, and nasopharyngitis were the most common TEAEs. Special interest TEAEs were infrequently reported. The most common was urinary retention and 2 TAM + MIRA patients required catheterization (neither led to discontinuation). No major changes in blood pressure or pulse rate were noted and similar electrocardiogram parameters were observed for both groups. Changes in mean postvoid residual volume and Qmax were not clinically meaningful. CONCLUSION: No unexpected safety concerns were noted in men receiving tamsulosin for lower urinary tract symptoms associated with benign prostatic hyperplasia who subsequently received mirabegron add-on therapy.
Authors: Ru Huang; Yuhan Liu; Anna Ciotkowska; Alexander Tamalunas; Raphaela Waidelich; Frank Strittmatter; Christian G Stief; Martin Hennenberg Journal: Front Pharmacol Date: 2021-06-24 Impact factor: 5.810