Assessment of the cardiac safety of fampridine-SR sustained-release tablets in a thorough QT/QTc evaluation at therapeutic and supratherapeutic doses in healthy individuals
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.
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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