Barrie March1, Tara Cardi. 1. PRACS Institute, Ltd, Fargo, ND 58104, USA. Barrie.March@cetero.com
Abstract
OBJECTIVE: To characterize the effects of a sustained-release formulation of fampridine (fampridine-SR) on QT interval in healthy subjects. METHODS: In a double-blind, double-dummy trial, healthy subjects were randomized to 5 days treatment with fampridine-SR at therapeutic (10 mg twice daily) or supratherapeutic (30 mg twice daily) doses, placebo or moxifloxacin (400 mg on treatment day 5). Digital 12-lead electrocardiograms were recorded before treatment and on day 5; blood samples determined fampridine concentrations. Central tendency analysis determined whether the upper limit of the CI for the QT (individual-corrected QT; QTcI) interval change exceeded 10 ms. Outlier analysis determined new-onset QT (corrected QT; QTc) intervals; maximum change in QTc from baseline of 30 - 60 ms and maximum change from baseline >or= 60 ms. The relationship between pharmacokinetic parameters and QTcI values is explored. RESULTS:Moxifloxacin was associated with a QTcI interval increase > 5 ms at 7 time points; no increase was observed with either dose of fampridine-SR; there were no fampridine outliers. Pharmacokinetic evaluation failed to find dose-dependent cardiac effects. Fampridine was well tolerated, with a higher frequency of adverse events at the supratherapeutic dose. CONCLUSION: This study showed that fampridine-SR at therapeutic and supratherapeutic doses was not associated with QT prolongation in healthy subjects.
RCT Entities:
OBJECTIVE: To characterize the effects of a sustained-release formulation of fampridine (fampridine-SR) on QT interval in healthy subjects. METHODS: In a double-blind, double-dummy trial, healthy subjects were randomized to 5 days treatment with fampridine-SR at therapeutic (10 mg twice daily) or supratherapeutic (30 mg twice daily) doses, placebo or moxifloxacin (400 mg on treatment day 5). Digital 12-lead electrocardiograms were recorded before treatment and on day 5; blood samples determined fampridine concentrations. Central tendency analysis determined whether the upper limit of the CI for the QT (individual-corrected QT; QTcI) interval change exceeded 10 ms. Outlier analysis determined new-onset QT (corrected QT; QTc) intervals; maximum change in QTc from baseline of 30 - 60 ms and maximum change from baseline >or= 60 ms. The relationship between pharmacokinetic parameters and QTcI values is explored. RESULTS:Moxifloxacin was associated with a QTcI interval increase > 5 ms at 7 time points; no increase was observed with either dose of fampridine-SR; there were no fampridine outliers. Pharmacokinetic evaluation failed to find dose-dependent cardiac effects. Fampridine was well tolerated, with a higher frequency of adverse events at the supratherapeutic dose. CONCLUSION: This study showed that fampridine-SR at therapeutic and supratherapeutic doses was not associated with QT prolongation in healthy subjects.
Authors: Emil Samara; Peter Winkle; Patricia Pardo; Herbert R Henney; Susan L Way; Eppie Brown; Angela Lee; Andrew R Blight Journal: J Clin Pharmacol Date: 2013-10-22 Impact factor: 3.126