Safety of Silodosin, a Highly Uroselective Alpha-1 Adrenergic Receptor Antagonist: Combined Results From an Open-Label Extension of 2 Randomized, Placebo-Controlled, Parallel-Group Studies

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Background: Silodosin is an alpha-1 adrenergic receptor antagonist that has demonstrated efficacy in treating lower urinary tract symptoms associated benign prostatic hyperplasia (BPH). A study was conducted to characterize the long-term safety of silodosin.
Methods: This extension study enrolled men ≥50 y old who had successfully completed either of 2 randomized, double-blind, placebo-controlled, parallel-group 12-week studies of silodosin treatment for symptomatic BPH. In the extension study, all patients received oral silodosin 8 mg once daily with breakfast for 40 weeks. Clinic visits occurred at weeks 0 (baseline), 2, 8, 16, 24, 32, and 40. Safety was evaluated by adverse events (AEs; assessed at each visit after baseline), vital signs and clinical laboratory tests (weeks 8, 16, and 40), electrocardiography (ECG; weeks 8 and 40), and physical examination (week 40). Efficacy was assessed by the International Prostate Symptom Score (IPSS) at week 40. The safety population included patients who received ≥1 dose of silodosin. The efficacy population included patients who completed the open-label study without significant deviations from protocol. Safety and efficacy data were summarized with descriptive statistics and frequency distributions. Last observation carried forward analysis was used for efficacy data.
Results: A total of 661 patients were enrolled, and 435 (65.8%) completed the extension study. Reasons given for discontinuation included adverse events (n=93; 14.1%), lack of efficacy (n=58; 8.8%), voluntary withdrawal (n=33; 5.0%), and various other causes (n=42; 6.4%). All 661 patients were included in the safety population; 429 (64.9%) were included in the efficacy population. For the safety population, the majority (n=600; 90.8%) of patients were Caucasian; the mean age (±standard deviation) was 64.8 ± 8.1 y. More than half of patients reported ≥1 AE; less than one third reported a drug-related AE (Table). AEs and drug-related AEs were more frequent in patients who had previously received placebo during double-blind treatment (Table). Serious AEs occurred in 4% to 5% of patients, regardless of previous treatment assignment. None of the serious AEs, which included 2 deaths, was drug-related. Retrograde ejaculation led to discontinuation of 26 patients (7.5%) previously given placebo and 6 patients (1.9%) previously given silodosin. Few patients in either group reported an AE of severe intensity (Table). Silodosin treatment was not associated with clinically meaningful changes in blood pressure, clinical laboratory parameters, ECG results, or physical examination findings. In the evaluable population, the IPSS decreased by 3.1 ± 6.6 points between weeks 0 and 40. Although the change was larger (−4.5 ± 6.7 points) in patients previously given placebo, the total score also decreased (−1.6 ± 6.0 points) in patients previously treated with silodosin.
Conclusions: Silodosin was well tolerated by most men with BPH during 40 weeks of open-label treatment. Retrograde ejaculation was the most common AE but did not lead to drug discontinuation in most cases. BPH symptoms improved during treatment with silodosin.

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