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.
Keywords:
ECG; QTc interval; anacetrapib; thorough QT.
© 2014, The American College of Clinical Pharmacology.
Publication types
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Clinical Trial
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Anti-Bacterial Agents / administration & dosage
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Anti-Bacterial Agents / adverse effects
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Anti-Bacterial Agents / blood
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Anti-Bacterial Agents / pharmacokinetics
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Anticholesteremic Agents / administration & dosage*
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Anticholesteremic Agents / adverse effects
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Anticholesteremic Agents / blood
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Anticholesteremic Agents / pharmacokinetics
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Arrhythmias, Cardiac / chemically induced
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Cholesterol Ester Transfer Proteins / antagonists & inhibitors*
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Cohort Studies
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Cross-Over Studies
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Dose-Response Relationship, Drug
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Double-Blind Method
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Drugs, Investigational / administration & dosage*
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Drugs, Investigational / adverse effects
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Drugs, Investigational / pharmacokinetics
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Electrocardiography / drug effects
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Female
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Fluoroquinolones / administration & dosage
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Fluoroquinolones / adverse effects
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Fluoroquinolones / blood
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Fluoroquinolones / pharmacokinetics
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Heart / drug effects*
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Humans
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Male
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Middle Aged
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Models, Biological*
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Moxifloxacin
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Oxazolidinones / administration & dosage*
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Oxazolidinones / adverse effects
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Oxazolidinones / blood
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Oxazolidinones / pharmacokinetics
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Topoisomerase II Inhibitors / administration & dosage
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Topoisomerase II Inhibitors / adverse effects
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Topoisomerase II Inhibitors / blood
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Topoisomerase II Inhibitors / pharmacokinetics
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Young Adult
Substances
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Anti-Bacterial Agents
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Anticholesteremic Agents
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Cholesterol Ester Transfer Proteins
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Drugs, Investigational
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Fluoroquinolones
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Oxazolidinones
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Topoisomerase II Inhibitors
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anacetrapib
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Moxifloxacin