Pharmacokinetics, Pharmacodynamics and Drug Interactions of Evacetrapib with Select Statins in Healthy Chinese Subjects

Aim: Evaluate steady-state pharmacokinetics and potential interactions between select statins and evacetrapib. Patients & methods: This open-label, two-part study included 62 healthy native Chinese subjects. Part 1 evaluated pharmacokinetics and pharmacodynamics of evacetrapib after 1 or 14 once-daily doses. Part 2 evaluated pharmacokinetics and pharmacodynamics of simvastatin, atorvastatin and evacetrapib administered alone, and of statin + evacetrapib coadministered. Results: Evacetrapib estimated accumulation ratio following once-daily dosing was 2.7. Simvastatin or atorvastatin coadministration reduced evacetrapib AUC0–24 by 12% (90% CI: -0.1 to -22%) or 10% (90% CI: -23–5%), respectively. Evacetrapib coadministration increased simvastatin or atorvastatin AUC0–24 by 123% (90% CI: 91–159%) or 16% (90% CI: 6–27%), respectively. Evacetrapib administered alone and with a statin increased high-density lipoprotein cholesterol, decreased low-density lipoprotein cholesterol, and was well tolerated. Conclusion: The significant increase in simvastatin exposure after evacetrapib coadministration was unexpected compared with previous evacetrapib and simvastatin interaction studies.