Effects of the cholesteryl ester transfer protein inhibitor evacetrapib on lipoproteins, apolipoproteins and 24-h ambulatory blood pressure in healthy adults.

ABSTRACT: We investigated the safety, tolerability, pharmacokinetics and pharmacodynamics of evacetrapib.Healthy volunteers received multiple daily doses of evacetrapib (10-600?mg) administered for up to 15 days in a placebo-controlled study.Mean peak plasma concentrations of evacetrapib occurred at 4-6?h and terminal half-life ranged 24-44?h. Steady state was achieved at approximately 10 days; all subjects had undetectable levels of evacetrapib 3 weeks after their last dose. The trough inhibition of cholesteryl ester transfer protein (CETP) activity was 65 and 84% at 100 and 300?mg, respectively. At the highest dose (600?mg), evacetrapib significantly inhibited CETP activity (91%), increased HDL-C (87%) and apo AI (42%), and decreased LDL-C (29%) and apo B (26%) relative to placebo. For the highest dose tested, levels of evacetrapib, CETP activity, CETP mass, HDL-C and LDL-C returned to levels at or near baseline after a 2-week washout period. Evacetrapib at the highest dose tested did not produce any significant effect on 24-h ambulatory systolic or diastolic blood pressure.Multiple doses of evacetrapib potently inhibited CETP activity, leading to substantial elevations in HDL-C and lowering of LDL-C. Evacetrapib was devoid of clinically relevant effects on blood pressure and mineralocorticoid levels.

SUBMITTER: Suico JG 

PROVIDER: S-EPMC4284021 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature