Evacetrapib
A high-fat breakfast raises steady-state evacetrapib exposure by 44%, with correspondingly larger lipid and CETP-activity changes (J Cardiovasc Pharmacol Ther 2015)
Original title: A Multidose Study to Examine the Effect of Food on Evacetrapib Exposure at Steady State
This randomized, two-period, two-sequence, open-label crossover study tested how a high-fat meal affects steady-state evacetrapib exposure. Forty healthy participants (34 men, 6 women; mean age 41.5 years, mean BMI 26.6 kg/m2) received evacetrapib 130 mg/d for 10 days after a 10-hour fast or after a high-fat breakfast each day, with plasma sampled through 24 hours and CETP activity, HDL-C, LDL-C, total cholesterol, and triglycerides also assessed. AUCtau was 44% higher (90% CI 29%-62%) and Cmax was 51% higher (90% CI 28%-79%) in the fed than fasted state, and consistent with this higher exposure, changes in HDL-C, LDL-C, and CETP activity were larger in the fed state, while total cholesterol and triglycerides showed no notable difference between states. Evacetrapib 130 mg was well tolerated with or without food, confirming a high-fat meal raises mean steady-state evacetrapib exposure by 44%.
Original abstract
Purpose: To determine the effect of a high-fat meal on evacetrapib exposure at steady state in healthy participants.
Methods: This was a randomized, 2-period, 2-sequence, open-label, crossover study. Patients were randomly assigned to 1 of the 2 treatment sequences in which they received evacetrapib 130 mg/d for 10 days following a 10-hour fast each day or following a high-fat breakfast each day. Plasma samples collected through 24 hours were analyzed for evacetrapib concentrations and pharmacokinetic parameter estimates including area under the concentration-time curve during a dosing interval (AUCτ), maximum observed concentration (Cmax), and time of Cmax (tmax) were calculated. Pharmacodynamic parameters, including cholesteryl ester transfer protein (CETP) activity, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, and triglycerides, were also assessed.
Results: A total of 34 males and 6 females, mean age 41.5 years and mean body mass index 26.6 kg/m(2), were enrolled. Statistical analysis showed AUCτ was 44% higher (90% confidence interval [CI]: 29%-62%) and Cmax was 51% higher (90% CI: 28%-79%) in the fed state than in the fasted state, indicating an effect of food. Consistent with higher evacetrapib exposure, changes in HDL-C, LDL-C, and CETP activity appeared to be greater in the fed state than in the fasted state. There were no notable changes in total cholesterol or triglycerides following administration in the fed and fasted states. The 130-mg doses of evacetrapib were well tolerated with and without food.
Conclusion: A high-fat meal increased evacetrapib mean exposure at steady state by 44% in healthy participants.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.