Silodosin, a new alpha1A-adrenoceptor-selective antagonist for treating benign prostatic hyperplasia: results of a phase III randomized, placebo-controlled, double-blind study in Japanese men.

ABSTRACT

OBJECTIVE: To verify the efficacy and safety of the new alpha1A-adrenoceptor-selective antagonist silodosin compared with tamsulosin and placebo in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: This randomized, double-blind, placebo-controlled study was conducted at 88 centres in Japan. Men aged > or = 50 years with an International Prostate Symptom Score (IPSS) of > or = 8, a quality-of-life (QoL) score of > or = 3, a maximum urinary flow rate (Qmax) of < 15 mL/s, a prostate volume of > or = 20 mL and a postvoid residual urine volume of < 100 mL were eligible for enrolment. Patients were randomized to receive silodosin 4 mg twice daily, tamsulosin 0.2 mg once daily, or placebo, for 12 weeks. The primary endpoint was the change in IPSS from baseline. Safety was assessed by adverse events, physical examination, vital signs and laboratory tests. RESULTS: In all, 457 patients were randomized (silodosin 176, tamsulosin 192 and placebo 89). The change in the total IPSS from baseline in the silodosin, tamsulosin and placebo groups was -8.3, -6.8 and -5.3, respectively. There was a significant decrease in the IPSS vs placebo in the silodosin group from 1 week. In the early-stage comparison, silodosin showed a significant decrease in IPSS vs tamsulosin at 2 weeks. The change in QoL from baseline was -1.7, -1.4 and -1.1 in the silodosin, tamsulosin and placebo groups, respectively; silodosin showed a significant improvement in the QoL score vs placebo. In the subgroup of patients with severe symptoms (IPSS > or = 20) silodosin also gave a significantly better improvement than placebo (-12.4 vs -8.7). The incidence rates of adverse events and drug-related adverse events were, respectively, 88.6%, 82.3% and 71.6% and 69.7%, 47.4% and 36.4%, respectively. The most common adverse event in the silodosin group was abnormal ejaculation, which occurred more often in the silodosin than in the tamsulosin group (22.3% vs 1.6%). However, only five men (2.9%) discontinued treatment for abnormal ejaculation. CONCLUSION: Silodosin was generally effective in the absence of obtrusive side-effects. This study suggests that silodosin is clinically useful for treating LUTS associated with BPH.