Rapid efficacy of the highly selective α(1A)-adrenoceptor antagonist silodosin in men with signs and symptoms of benign prostatic hyperplasia: pooled results of 2 phase 3 studies.

PURPOSE We evaluated the efficacy and safety of silodosin for treatment of benign prostatic hyperplasia symptoms in 2 randomized, placebo controlled, phase 3 studies. MATERIALS AND METHODS Men 50 years or older with an International Prostate Symptom Score of 13 or greater and peak urinary flow rate of 4 to 15 ml per second received placebo or 8 mg silodosin daily with breakfast for 12 weeks. The primary end point was International Prostate Symptom Score change from baseline to last observation. Change in peak urinary flow rate was a secondary end point. Differences in treatment efficacy were assessed by ANCOVA. RESULTS Of 923 patients (mean age 65 years) 466 received silodosin and 457 placebo. After 0.5 week (range 3 to 4 days) of treatment patients receiving silodosin vs placebo achieved significant improvement in total International Prostate Symptom Score (difference -1.9, p <0.0001) and irritative (-0.5, p = 0.0002) and obstructive (-1.4, p <0.0001) subscores. The mean ± SD change from baseline in total International Prostate Symptom Score was -4.2 ± 5.3 for silodosin vs -2.3 ± 4.4 for placebo. Differences (silodosin vs placebo) in International Prostate Symptom Score and subscores increased by week 12 (p <0.0001). Mean change from baseline in peak urinary flow rate (ml per second) 2 to 6 hours after initial dose was greater (p <0.0001) with silodosin (2.8 ± 3.4) than placebo (1.5 ± 3.8). Differences remained significant (p <0.001) through week 12. The most common treatment emergent adverse event was (mostly mild) retrograde ejaculation (silodosin 28.1% of patients, placebo 0.9%). Few patients receiving silodosin (2.8%) discontinued because of retrograde ejaculation. Proportions of patients with treatment emergent orthostatic hypotension were similar for silodosin (2.6%) and placebo (1.5%). CONCLUSIONS Treatment with silodosin produced rapid improvement in urinary symptoms that was sustained for 12 weeks. Silodosin was well tolerated with a low incidence of orthostatic hypotension.