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 AUC_0–24 by 12% (90% CI: -0.1 to -22%) or 10% (90% CI: -23–5%), respectively. Evacetrapib coadministration increased simvastatin or atorvastatin AUC_0–24 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.

Keywords:

Papers of special note have been highlighted as: • of interest

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Vol. 3, No. 2

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History

Received 29 September 2017

Accepted 23 March 2018

Published online 29 May 2018

Published in print May 2018

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Keywords

Acknowledgements

The authors wish to thank the subjects who participated in this study, S Hall, K Hillgren, Y Guo, M Mohutsky and MM Posada, as well as S Hullett of Eli Lilly and Company (IN, USA) for their assistance with the CYP3A5 hypothesis and generation of in vitro data and predictions.

Financial & competing interests disclosure

This study was sponsored by Eli Lilly and Company, IN, USA. E Cannady, D Small, P Xin, M-D Wang, J Jin and J Suico are employees of, and may hold stock in, Eli Lilly and Company. Y Liang, Y Cui and X Zhao are employees of Peking University First Hospital. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was provided by A Hodgson, Covance Inc. (WI, USA) and was funded by Eli Lilly and Company.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

ClinicalTrials.gov Identifier: NCT02156492

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