Mirabegron Add-on Therapy Safe and Effective in Men Receiving Tamsulosin for LUTS Associated with BPH

16 Dec, 20

Introduction

The efficacy and safety of mirabegron vs placebo for treating overactive bladder (OAB) symptoms was assessed in men concurrently receiving tamsulosin for lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) by the multicentric PLUS trial. The results demonstrated statistically significant clinical improvements with the administration of tamsulosin and mirabegron as compared to tamsulosin plus placebo. Although the safety of mirabegron and tamsulosin as monotherapies has been comprehensively studied, there is paucity of clinical data on the use of the agents in combination.

Aim

To analyze the safety of mirabegron add-on therapy in men with OAB symptoms concurrently receiving tamsulosin for LUTS associated with BPH.

Patient Profile

Men aged ≥40 years with OAB symptoms (≥8 micturitions/day and ≥2 urgency episodes/day) who had received BPH treatment with tamsulosin (0.4 mg daily)

Method

Study Design

Phase 4, randomized, double-blind, multicenter trial.

Treatment Strategy

The Phase 4 PLUS study comprised a 4-week run-in period (tamsulosin 0.4 mg) followed by a 12-week randomized double-blind treatment period (add-on treatment: mirabegron 25 mg or placebo).
Doses were increased to mirabegron 50 mg or matched placebo after 4 weeks.

Endpoints

Treatment-emergent adverse events (TEAEs)
Vital signs
12-lead electrocardiograms
Changes in postvoid residual volume
Maximum urinary flow (Q_max)

Results

The safety analysis set comprised 352 tamsulosin plus mirabegron (TAM+MIRA) and 354 tamsulosin plus placebo (TAM+PL) patients.
More than half of the study population were ≥65 years old with approximately 1 in 8 patients ≥75 years old (90 [12.7%] patients
And the most common comorbidity was hypertension
The TAM+PL group had a higher frequency of overall TEAEs although a higher incidence of drug-related TEAEs was observed with TAM+MIRA.
Overall, over 90% of the TEAEs reported in PLUS were mild or moderate in severity as seen in Figure 1.

Figure 1. Incidence of TEAEs

Drug-related serious TEAEs were reported by 3 patients (2 TAM + MIRA patients: acute myocardial infarction with cerebral infarction and angina pectoris, 1 TAM + PL patient: lacunar stroke).
The most common TEAEs were hypertension, headache, and nasopharyngitis
Special interest TEAEs were infrequently reported.
The most common was urinary retention, with 2 TAM + MIRA patients requiring catheterization (neither led to discontinuation).
Both the groups did not demonstrate any major changes in blood pressure or pulse rate and had comparable electrocardiogram parameters
Changes in mean PVR and Q_max were not clinically significant.

Conclusion

The results of this first North American and European study showed no unexpected safety concerns and a similar safety profile of mirabegron add-on therapy to that expected for the individual monotherapies in men with overactive bladder symptoms associated with benign prostatic hyperplasia receiving tamsulosin.

Urology.2020 Oct. Doi:10.1016/j.urology.2020.09.040.