title: Effect of the thrombin receptor antagonist (PAR-1) vorapaxar on QT/QTc interval in healthy volunteers: A randomized, placebo- and positive-controlled, parallel group trial.
abstract: In a randomized, double-blind (vorapaxar and placebo), placebo- and positive-controlled (moxifloxacin 400 mg) parallel group study, the effect of single-dose vorapaxar 120 mg on QT/QTc interval was assessed in 120 adults 18-50 years. Twelve-lead digital ECGs were obtained in triplicate using Mortara H12+ Holter monitors at 9 timepoints over 24 hours. If the largest upper bound of the 95% one-sided CI for the mean difference in QTcF between vorapaxar and placebo was <10 milliseconds, vorapaxar was considered to have no potential for QT/QTc prolongation of regulatory concern. Vorapaxar was well-tolerated. The lower bound of the 95% CI for the difference in QTcF between moxifloxacin and placebo was >5 milliseconds, confirming study sensitivity. Vorapaxar had no significant effect on QTcF. At all timepoints the upper 95% CI for the mean difference between placebo and vorapaxar was ≤3.8 milliseconds (mean difference ≤1.0 milliseconds). Vorapaxar does not prolong the QT/QTc interval in healthy subjects.
authors.affiliation: Merck & Co., Inc., Whitehouse Station, New Jersey.
authors.forename: Teddy
authors.initials: T
authors.lastname: Kosoglou
authors.affiliation: PPD Development LP, Austin, Texas.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Hunt
authors.affiliation: Merck & Co., Inc., Whitehouse Station, New Jersey.
authors.forename: Fengjuan
authors.initials: F
authors.lastname: Xuan
authors.affiliation: Merck & Co., Inc., Whitehouse Station, New Jersey.
authors.forename: Bharath
authors.initials: B
authors.lastname: Kumar
authors.affiliation: Merck & Co., Inc., Whitehouse Station, New Jersey.
authors.forename: Paul
authors.initials: P
authors.lastname: Statkevich
authors.affiliation: Merck & Co., Inc., Whitehouse Station, New Jersey.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Hanson
authors.affiliation: Merck & Co., Inc., Whitehouse Station, New Jersey.
authors.forename: David L
authors.initials: DL
authors.lastname: Cutler
keywords: PAR-1; QT/QTc prolongation; cardiac safety; thrombin receptor antagonist; vorapaxar