Even at 8 times the therapeutic dose, anacetrapib does not clinically prolong the QTcF interval (J Clin Pharmacol 2014)

Anacetrapib is a cholesteryl ester transfer protein inhibitor in Phase III development. This double-blind, double-dummy, randomized, placebo- and active-comparator-controlled, 4-period, balanced crossover study evaluated the effects of anacetrapib (100 mg and 800 mg) on QTcF interval in healthy subjects. QTcF measurements were made up to 24 h following administration of single doses of anacetrapib 100 or 800 mg, moxifloxacin 400 mg, or placebo in the fed state. The primary hypothesis was supported if the 90% CI for the least squares (LS) mean differences between anacetrapib 800 mg and placebo in QTcF interval change from baseline were entirely <10 msec at every post-dose time point (1, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 h). The upper bounds of the 90% CIs for LS mean differences from placebo in changes from baseline in QTcF intervals for anacetrapib 100 and 800 mg were <5 msec at every time point. In conclusion, single doses of anacetrapib 100 and 800 mg do not prolong the QTcF interval to a clinically meaningful degree relative to placebo and are generally well tolerated in healthy subjects.