α1-Blockers have been used for the first line treatment of benign prostatic hyperplasia (BPH). Phosphodiesterase (PDE) 5 inhibitors (tadalafil) are recently used for the treatment of BPH. The combination therapy or add-on of an anticholinergic or a β3-adrenoceptor agonist (mirabegron) with α1-blocker is recommended for the treatment of BPH with overactive bladder (OAB). However, the efficacy of add-on treatment of mirabegron with tadalafil has not been reported. In the preset study, we evaluated efficacy and safety of add-on treatment of mirabegron (50mg/day) for OAB /BPH patients who were not satisfied with tadalafil (5mg/day) monotherapy for 8 weeks or longer.
Male Patients are with BPH, aged 50 to 89 years, with PVR <=150 mL and Qmax >=5 mL/sec and with remaining OAB symptoms even after administering tadalafil 5mg/day for more than 8 weeks. The patients were randomly assigned to either tadalafil monotherapy group (TG: 5mg,OD) or tadalafil/mirabegron combination therapy group (TMG: 5mg/50mg,OD) and were followed for 12 weeks. The primary endpoint was change from baseline in total overactive bladder symptom score (OABSS). The secondary endpoints were changes in each question of OABSS, IPSS, QOL index, micturition chart variables (number of voids/24 h, number of urinary urgency episodes/24 h, number of urgency incontinence episodes/24 h,), postvoid residual urine volume, and Qmax. At weeks 4 and 12, efficacy and safety were evaluated. A web-based system, eClinical Base (Translational Research Informatics Center, Kobe, Japan), was used for the assignment of patients after necessary data for patient registration were input by investigators and the patients were confirmed to meet the eligibility criteria. This study was approved by the ethics committee at each medical institution and written informed consent was obtained from each patient.
A total of 176 patients were randomized to either TG (87 patients) or TMG (89 patients). The number of safety analysis set was 87 and 87 (excluding two no-dosing) and the number of full analysis set was 80 and 81 in TG and TMG, respectively. The baseline characteristics of patients in the two groups were similar. The total OABSS (95% confidence interval) of TMG at 12 weeks was significantly decreased by 1.75 (0.93-2.56) point than that of TG (both sided P<0.00001). One severe adverse event (1.2%) was noted in TG (pain in hip joint) and seven mild adverse events (8.1%) in TMG.
The present study is the first report on treatment with PDE5 inhibitor and β3 agonist combination regimen. It was suggested that the effect of tadalafil/mirabegron combination therapy on relieving OAB symptoms appeared to be greater than that of tadalafil monotherapy and tadalafil/mirabegron combination therapy can be safely used.
