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 ≥ 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.

Keywords::

• fampridine
• MS
• potassium channels
• QT interval

Acknowledgements

The authors thank EJ Bienen of the Curry Rockefeller Group, LLC, for his editorial support in the preparation of this manuscript.

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