Evacetrapib
At the highest dose, evacetrapib inhibits CETP by 91% and raises HDL-C by 87% without moving 24-hour blood pressure (J Pharm Pharmacol 2014)
Original title: Effects of the cholesteryl ester transfer protein inhibitor evacetrapib on lipoproteins, apolipoproteins and 24-h ambulatory blood pressure in healthy adults
Healthy volunteers received multiple daily doses of evacetrapib (10-600 mg) for up to 15 days in a placebo-controlled study assessing safety, tolerability, pharmacokinetics, and pharmacodynamics. Mean peak plasma concentrations occurred at 4-6 hours, terminal half-life ranged 24-44 hours, steady state was reached at approximately 10 days, and evacetrapib was undetectable 3 weeks after the last dose. Trough CETP inhibition was 65% and 84% at 100 and 300 mg. At the highest dose (600 mg), evacetrapib significantly inhibited CETP activity (91%), raised HDL-C (87%) and apoAI (42%), and lowered LDL-C (29%) and apoB (26%) relative to placebo, with all these measures returning to near baseline after a 2-week washout. Evacetrapib at the highest dose produced no significant effect on 24-hour ambulatory systolic or diastolic blood pressure, confirming potent, dose-dependent CETP inhibition and lipid effects without clinically relevant blood pressure or mineralocorticoid effects.
Original abstract
Objectives: We investigated the safety, tolerability, pharmacokinetics and pharmacodynamics of evacetrapib.
Methods: Healthy volunteers received multiple daily doses of evacetrapib (10-600 mg) administered for up to 15 days in a placebo-controlled study.
Key Findings: 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.
Conclusions: 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.