A randomized, double-blind, placebo-controlled, multi-center, phase III clinical trial to investigate silodosin in the treatment of benign prostatic hyperplasia

Abstract

Objective To verify the efficacy and safety of the highly selective α1A-adrenoceptor antagonist silodosin in the treatment of lower urinary tract symptoms caused by benign prostatic hyperplasia.Methods A randomized,double-blind,placebo-controlled,multi-center study was performed.Patients with benign prostatic hyperplasia who met the inclusion/exclusion criteria were randomly assigned to silodosin (8 mg/day) group or placebo group (2:1).A total of 501 subjects were enrolled and included in the Full Analysis Set (FAS),338 in silodosin group and 163 in placebo group.479 subjects were included in the Per-Protocol (PP) Set,325 in silodosin group and 154 in placebo group.The treatment duration was 12 weeks.The primary endpoint was IPSS change from baseline at Week 12.The secondary endpoints were QOL score before and after the treatment,maximun flow rate (Qmax),average urinary flow rate (Qave),and the change in residual urine volume.At baseline,IPSS were 20.87 ± 5.03 in silodosin group and 20.99 ±4.80 in placebo group.Meanwhile in both group,QOL score were 4.95 ± 0.67 and 4.99 ± 0.69 ; Qmax were (10.82±2.73) ml/s and (10.31 ±2.74) ml/s; Qave were (5.70 ±2.11) ml/s and (5.48± 1.86)ml/s ; residual urine volume were (20.17 ± 23.72) ml and (18.45 ± 19.66) ml.The evaluation also included change of total IPSS in the early stage of drug administration (i.e.Week 1 or 2).Adverse events during the course of treatment were closely and recorded for safety evaluation.Results The change of IPSS from baseline at Week 12 was-7.17 ±6.44 for silodosin vs-5.77 ±5.95 for placebo (P ＜0.05).In early stage of drug administration,there were statistically significant differences between silodosin and placebo group in terms of IPSS changes from baseline at Week 1 (-2.29 ± 3.53 vs-1.25 ± 2.95,P ＜ 0.05)and Week2 (-3.42±4.43 vs-2.01 ±3.77,P＜0.05),respectively.The change of QOL score before and after treatment was-1.74 ± 1.37 for silodosin vs-1.40 ± 1.31 for placebo (P ＜ 0.05).123 adverse events occurred in silodosin group with the occurrence rate of 35.86％,including ejaculation failure,dry mouth,dizziness and bradycardia,and 39 adverse events occurred in placebo group with the occurrence rate of 23.21％,including dizziness,skin rash,bradycardia,and dry mouth.Conclusions Silodosin is a fast acting medication,which can significantly improve self-reported symptoms in patients with benign prostatic hyperplasia and enhance their quality of life.Silodosin is effective and safe in the treatment of voiding disorders caused by benign prostatic hyperplasia. Key words: Benign prostatic hyperplasia; Drug therapy; Silodosin; Clinical research