Efficacy and Safety of Silodosin in the Treatment of the Signs and Symptoms of Benign Prostatic Hyperplasia (BPH): Pooled Results of 2 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase 3 Studies

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Background: Silodosin, a uroselective α-adrenergic antagonist, is currently being evaluated for the treatment of BPH-associated lower urinary tract symptoms. Its extremely high α_1A- to α_1B-receptor selectivity is expected to increase cardiovascular safety compared with less-selective antagonists. Two identical multicenter, double-blind, placebo-controlled, parallel-group phase 3 studies were conducted to evaluate the efficacy and safety of silodosin in patients with moderate to severe BPH.
Methods: Generally healthy men, ≥50 y old, with signs and symptoms of BPH (peak urine flow rate [Qmax] between 4 and 15 mL/sec and International Prostate Symptom Score [IPSS] ≥13), received 8 mg silodosin or placebo once daily (with breakfast) for 12 weeks. The primary and secondary end points were changes from baseline in IPSS and Qmax, respectively. IPSS irritative and obstructive subscores were additional efficacy variables. The significance of differences in treatment efficacy (silodosin vs placebo), based on least squares (LS) mean changes from baseline to the last observation carried forward, were assessed by ANCOVA.
Results: Of 923 patients who had at least 1 primary efficacy evaluation, 466 received silodosin and 457 received placebo. The 2 treatment groups had similar demographic characteristics: most patients were Caucasians; average age was ~65 y (Table 1). Discontinuation rate was 10% overall and slightly higher among patients receiving silodosin (n=53, 11.4%) compared with those receiving placebo (n=38, 8.3%). Mean baseline values for efficacy variables were also very similar in both treatment groups (Table 1). Silodosin significantly improved urinary symptoms, including IPSS, irritative and obstructive IPSS subscores, and Qmax, compared with placebo (Table 2). The total number of patients experiencing at least 1 adverse event was higher among patients receiving silodosin (55.2%) than among those receiving placebo (36.8%), largely attributable to a relatively high incidence of mostly mild retrograde ejaculation. The incidence of treatment-related orthostatic hypotension was similar in the silodosin (n=9, 1.9%) and placebo (n=7; 1.5%) groups. Incidences of treatment-related dizziness and headache were low and only slightly higher among silodosin- than placebo-treated patients. No treatment-related cardiac events or hypertension was reported. One treatment-related serious adverse event occurred in the course of both studies: an 85-year-old patient who was concurrently taking an excluded medication, prazosin, experienced syncope and discontinued treatment with silodosin.
Conclusions: Silodosin significantly improved urinary symptoms (IPSS, irritative IPSS, obstructive IPSS, and Qmax), was well tolerated overall, and had a placebo-like effect on blood pressure. Most adverse events were mild and related to retrograde ejaculation.

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