title: Single therapeutic and supratherapeutic doses of anacetrapib, a cholesteryl ester transfer protein inhibitor, do not prolong the QTcF interval in healthy volunteers.
abstract: 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.
authors.affiliation: Merck & Co. Inc., Whitehouse Station, NJ, USA.
authors.forename: Brett
authors.initials: B
authors.lastname: Lauring
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiujiang Susie
authors.initials: XS
authors.lastname: Li
authors.forename: Patrick
authors.initials: P
authors.lastname: Larson
authors.forename: Allison
authors.initials: A
authors.lastname: Moreau
authors.forename: H Frank
authors.initials: HF
authors.lastname: Farmer
authors.forename: Amy O
authors.initials: AO
authors.lastname: Johnson-Levonas
authors.forename: John A
authors.initials: JA
authors.lastname: Wagner
authors.forename: Eseng
authors.initials: E
authors.lastname: Lai
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors*; D015331:Cohort Studies; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015507:Drugs, Investigational / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D006321:Heart / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D000077266:Moxifloxacin; D023303:Oxazolidinones / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D059005:Topoisomerase II Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000924:Anticholesteremic Agents; D053480:Cholesterol Ester Transfer Proteins; D015507:Drugs, Investigational; D024841:Fluoroquinolones; D023303:Oxazolidinones; D059005:Topoisomerase II Inhibitors; C530884:anacetrapib; D000077266:Moxifloxacin
keywords: ECG; QTc interval; anacetrapib; thorough QT