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2008 Annual Meeting Abstracts
Double-Blind, Randomized, Parallel-Group Study to Define Electrocardiographic Effects of Silodosin, a Uroselective α-Adrenergic Antagonist
Herbert Lepor1, Gary Hoel2, Lawrence Hill2, Weining Volinn2
1NYU School of Medicine, New York City, NY;2Watson Laboratories, Salt Lake City, UT
Introduction: This double-blind, randomized, parallel-group study compared the QTc effects of therapeutic and supratherapeutic doses of silodosin versus those of placebo and a positive control (moxifloxacin).
Methods: Healthy men (N = 186; 18-45 y) were randomized to receive silodosin (8 or 24 mg) or placebo for 5 days, or moxifloxacin (400 mg) once on day 5. ECGs were obtained with a Mortara Instrument H12 Plus continuous 12-lead ECG digital recorder. Five ECGs were extracted within a 1-3 min window at baseline (day −1) and on day 5 at −0.25, 1, 1.5, 2, 3, 4, 6, 8, 10, and 23.5 hr from dosing. Time-matched and time-averaged ECG parameters were analyzed with ANCOVA. (Central ECG laboratory blinded to treatment.)
Results: Time-matched analysis for placebo-corrected change from baseline in QTcI at day 5 revealed no upper limits >10 ms (noninferiority bound). (Figure) Placebo-corrected QTcI mean changes from baseline for clinical and supratherapeutic doses of silodosin were −1.7 and 1.4 ms, respectively; placebo was −0.8 ms and moxifloxacin 4.0 ms. Outlier analysis, morphologic review, and pharmacokinetic-pharmacodynamic modeling showed no meaningful effects. No statistically significant correlation was observed for maximum plasma concentration and QTcI change for silodosin or metabolites.
Conclusions: In this thorough ECG study, silodosin had no meaningful effects on heart rate, PR and QRS interval duration, or cardiac repolarization. 
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