Absence of QTc prolongation with betrixaban: a randomized, double-blind, placebo- and positive-controlled thorough ECG study.
Expert Opin Pharmacother
; 14(1): 5-13, 2013 Jan.
Article
em En
| MEDLINE
| ID: mdl-23216423
ABSTRACT
OBJECTIVE:
To evaluate the effects of the anticoagulant betrixaban on individual heart rate-corrected QT (QTcI). RESEARCH DESIGN ANDMETHODS:
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 OUTCOMESMEASURES:
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piridinas
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Benzamidas
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Síndrome do QT Longo
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Eletrocardiografia
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Frequência Cardíaca
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Anticoagulantes
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article