title: Effects of the selective alpha 1a-adrenoceptor antagonist silodosin on ECGs of healthy men in a randomized, double-blind, placebo- and moxifloxacin-controlled study.
abstract: In order to determine the effects of therapeutic and supratherapeutic doses of silodosin on QT interval, healthy men (N = 186; aged 18-45 years) were randomized to receive silodosin (8 or 24 mg) or placebo for 5 days or moxifloxacin 400 mg (positive control, known to prolong QT) once on day 5. At baseline and on day 5, five ECGs were recorded 0.25 h before dosing and 1, 1.5, 2, 3, 4, 6, 8, 10, and 23.5 h after dosing. Adjusted mean differences (analysis of covariance) between silodosin and placebo in the change in individual heart rate-corrected QTc (QTcI) from baseline to day 5 were <5 ms at all times (all 90% confidence interval (CI) upper limits <10 ms). The QTcI difference for moxifloxacin compared with placebo often exceeded 5 ms, establishing assay sensitivity. For silodosin, no statistically or clinically significant correlation was seen between plasma concentration and QTcI, and no clinically important effects on heart rate, PR segment, QRS complex, or morphologic ECG data were observed.
authors.affiliation: eResearch Technology, Inc., Philadelphia, Pennsylvania, USA.
authors.forename: J
authors.initials: J
authors.lastname: Morganroth
authors.forename: H
authors.initials: H
authors.lastname: Lepor
authors.forename: L A
authors.initials: LA
authors.lastname: Hill
authors.forename: W
authors.initials: W
authors.lastname: Volinn
authors.forename: G
authors.initials: G
authors.lastname: Hoel
mesh_terms: D000293:Adolescent; D058668:Adrenergic alpha-1 Receptor Antagonists; D000328:Adult; D001372:Aza Compounds / Q000494:pharmacology*; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects*; D024841:Fluoroquinolones; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D008133:Long QT Syndrome / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D011804:Quinolines / Q000494:pharmacology*; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D055815:Young Adult
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D001372:Aza Compounds; D024841:Fluoroquinolones; D007211:Indoles; D011804:Quinolines; D018340:Receptors, Adrenergic, alpha-1; C095285:silodosin; D000077266:Moxifloxacin