Evacetrapib
A thorough QT study finds evacetrapib safe on cardiac rhythm even at 5-fold the exposure planned for phase 3 (J Cardiovasc Pharmacol Ther 2014)
Original title: Evacetrapib at a supratherapeutic steady state concentration does not prolong QT in a thorough QT/QTc study in healthy participants
This single-center, randomized, active- and placebo-controlled, three-period crossover study tested whether evacetrapib prolongs the QT interval. Participants (73.2% male, mean age 43.1 years, mean BMI 25.9 kg/m2) received evacetrapib 1200 mg daily for 10 days (a supratherapeutic dose), moxifloxacin 400 mg for 1 day (positive control), or placebo for 10 days, comparing the effect of evacetrapib on the population-corrected QT interval to placebo at 7 timepoints on day 10, with a two-sided 90% CI upper bound under 10 milliseconds confirming no significant effect. The upper bound stayed under 10 milliseconds at every timepoint, while moxifloxacin raised QTcP by at least 5 milliseconds at every measured timepoint, confirming assay sensitivity. Evacetrapib peak concentration occurred at a median of about 2 hours with an elimination half-life of about 41 hours, and AUC and Cmax were approximately 5-fold the exposure expected at the phase 3 dose, with the 1200 mg dose well tolerated over 10 days.
Original abstract
Purpose: To evaluate whether evacetrapib prolongs QT intervals in healthy participants.
Methods: This was a single-center, randomized, active and placebo-controlled, 3-period, 6-sequence, and crossover study. Participants were randomized to 1 of 6 treatment sequences in which they received 1 of 3 treatments: evacetrapib 1200 mg daily for 10 days (supratherapeutic dose), moxifloxacin 400 mg for 1 day (positive control), or placebo for 10 days in each of the 3 separate treatment periods. Electrocardiographic parameters were recorded at time points specified in the protocol. The primary end point was the comparison of evacetrapib effect on the population-corrected QT interval (QTcP) to that of placebo at 7 time points following dosing on day 10. An upper limit of the 2-sided 90% confidence interval (CI) <10 milliseconds confirmed the absence of significant effect. Pharmacokinetic parameters were also calculated.
Results: Subjects were predominantly male (73.2%) with a mean age of 43.1 years and a mean body mass index of 25.9 kg/m(2). For the primary analysis, the upper bound of the 2-sided 90% CI for the mean difference between evacetrapib and placebo was <10 milliseconds at all time points on day 10. Following administration of moxifloxacin, the QTcP increased by ≥5 milliseconds at all time points (2, 3, and 4 hours postdose). Maximum plasma concentrations of evacetrapib occurred at a median time of approximately 2 hours, and the mean apparent elimination half-life was approximately 41 hours. The area under the curve and Cmax achieved in this study were both ∼5-fold the values that are expected with the dose level being studied in a phase 3 cardiovascular outcome study. A 1200-mg supratherapeutic dose of evacetrapib was considered to be well tolerated after 10 days of daily dosing in healthy participants.
Conclusions: Evacetrapib is not associated with QT interval prolongation, even at supratherapeutic doses.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.