title: Absence of QTc prolongation with betrixaban: a randomized, double-blind, placebo- and positive-controlled thorough ECG study.
abstract: OBJECTIVE
  To evaluate the effects of the anticoagulant betrixaban on individual heart rate-corrected QT (QTcI).
  
  
  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.
  
  
  METHODS
  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.
authors.affiliation: eResearch Technology, Inc., Philadelphia, PA, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Morganroth
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Gretler
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Hollenbach
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Lambing
authors.forename: Uma
authors.initials: U
authors.lastname: Sinha
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001372:Aza Compounds / Q000009:adverse effects; D001549:Benzamides / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D024841:Fluoroquinolones; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008133:Long QT Syndrome / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D011804:Quinolines / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000925:Anticoagulants; D001372:Aza Compounds; D001549:Benzamides; D024841:Fluoroquinolones; D011725:Pyridines; D011804:Quinolines; C543086:betrixaban; D000077266:Moxifloxacin