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Betrixaban is an oral factor Xa inhibitor with a long half life, low renal clearance and is not metabolized by cytochrome P450 enzymes. Betrixaban is currently being studied for the prevention of venous thromboembolism in high risk acutely ill medical patients. The APEX trial is a randomized, double blind, active controlled, multinational Phase 3 study comparing extended duration (35–42 days) betrixaban prophylaxis to the standard of care, enoxaparin for 10 days.
To evaluate the effects of betrixaban on individual heart rate-corrected QT duration (QTcl), 96 healthy adults were randomly assigned to single-dose betrixaban 80 mg and 140 mg (therapeutic and supratherapeutic doses, respectively), placebo, and moxifloxacin 400 mg (positive control) in a 4-period crossover study. Electrocardiograms [ECGs] were recorded at predose and post dose hours 1, 2, 3, 4, 5, 6, 8, 12, 16, and 24. An analysis of covariance determined the placebo-corrected, time-matched mean change from baseline QTcl at the 95% upper confidence interval (UCI; 1-sided). The clinically significant change for betrixaban-treated groups was pre-specified as >10 ms (95% UCI, 1-sided). The observed mean QTcl 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 QTcl duration confirmed the absence of effect on QT. No clinically relevant changes were observed for other ECG parameters. The study included individual subjects whose maximum plasma concentration of betrixaban reached 10 fold higher concentration than that projected for doses used in the APEX study. Betrixaban was well tolerated in this ICH E14 thorough ECG study.
Poster Sessions, Expo North
Saturday, March 09, 2013, 10:00 a.m.-10:45 a.m.
Session Title: Arrhythmias: Basic Science and Atrial Fibrillation
Abstract Category: 5. Arrhythmias: Basic
Presentation Number: 1106-47
- 2013 American College of Cardiology Foundation