Absence of QTc prolongation with betrixaban: a randomized, double-blind, placebo- and positive-controlled thorough ECG study.

OBJECTIVE

To evaluate the effects of the anticoagulant betrixaban on individual heart rate-corrected QT (QTcI).

RESEARCH DESIGN AND

METHODS

Ninety-six healthy adults were randomly assigned to single-dose betrixaban 80 and 140 mg (therapeutic and supratherapeutic doses, respectively), placebo, and moxifloxacin 400 mg (positive control) in a four-period crossover study. Electrocardiograms were recorded at pre-dose and post-dose hours 1, 2, 3, 4, 5, 6, 8, 12, 16 and 24.

MAIN OUTCOMES MEASURES: An analysis of covariance determined the placebo-corrected, time-matched mean change from baseline QTcI at the 95% upper confidence interval (UCI; one-sided). The pre-specified clinically significant change for betrixaban-treated groups was > 10 ms (95% UCI, one-sided). Subjects were monitored for safety and tolerability.

RESULTS

Mean QTcI change was < 10 ms for both betrixaban groups at all time points; expected changes were observed for moxifloxacin, establishing assay sensitivity. Correlation between betrixaban plasma concentration and QTcI duration confirmed the absence of effect on QT.

CONCLUSIONS

Betrixaban at therapeutic and supratherapeutic doses did not cause clinically relevant changes in QTcI intervals or other electrocardiographic parameters. Betrixaban was well tolerated.