@article{b8e11bd6ab344844ba1826b8b345ab71,
title = "Lipids, safety parameters, and drug concentrations after an additional 2 years of treatment with Anacetrapib in the DEFINE study",
abstract = "Anacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor that has previously been shown to reduce low-density lipoprotein cholesterol (LDL-C) and raise high-density lipoprotein cholesterol (HDL-C) in patients with or at high risk of coronary heart disease in the 76-week, placebo-controlled, Determining the Efficacy and Tolerability of CETP Inhibition with Anacetrapib (DEFINE) trial. Here, we report the results of the 2-year extension to the DEFINE study where patients (n = 803) continued on the same assigned treatment as in the original 76-week study. Treatment with anacetrapib during the 2-year extension was well tolerated with a safety profile similar to patients on placebo. No clinically important abnormalities in liver enzymes, blood pressure, electrolytes, or adverse experiences were observed during the extension. At the end of the extension study, relative to the original baseline value, anacetrapib reduced Friedewald-calculated LDL-C by 39.9% and increased HDL-C by 153.3%, compared to placebo. The apparent steady state mean plasma trough concentration of anacetrapib was ∼640 nmol/L. Geometric mean plasma concentrations of anacetrapib did not appear to increase beyond week 40 of the 2-year extension of the 76-week DEFINE base study. In conclusion, an additional 2 years of treatment with anacetrapib were well tolerated with durable lipid-modifying effects on LDL-C and HDL-C.",
keywords = "anacetrapib, lipids, long-term safety, plasma concentrations",
author = "Gotto, {Antonio M.} and Uma Kher and Chatterjee, {Manash Shankar} and Yang Liu and Li, {Xiujiang Susie} and Sanskruti Vaidya and Cannon, {Christopher P.} and Brinton, {Eliot A.} and Moon, {Jennifer E.} and Sukrut Shah and Dansky, {Hayes M.} and Yale Mitchel and Philip Barter",
note = "Funding Information: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Antonio Gotto serves on the board of directors of Aegerion Pharmaceuticals, Arisaph Pharmaceuticals, and Esperion Therapeutics; as a consultant for Kowa and Merck; and on an advisory board for Dupont and Vatera Capital. Christopher Cannon receives research grants/support from Accumetrics, AstraZeneca, Boehringer-Ingelheim, CSL-Behring, Essentialis, GlaxoSmithKline, Merck, Regeneron, Sanofi, and Takeda; serves on advisory boards for Alnylam, Bristol-Myers Squibb, Lipimedix, and Pfizer but donates funds to charity; and is a clinical advisor and has equity in Automedics Medical Systems. Eliot Brinton serves on a medical advisory board for Atherotech, Inc; receives compensation for consultancy and/or lectures from Abbvie, Amarin, Arisaph, AstraZeneca, Atherotech, Inc, Daiichi Sankyo Inc, Essentialis, Kowa Pharmaceuticals, Merck & Co, Sanofi-Aventis, and Takeda Pharmaceuticals; and receives research support from Amarin, Health Diagnostic Laboratory, Merck & Co, and Roche. Philip Barter serves on advisory boards for MSD and Kowa; serves as a consultant for CSL-Behring; receives grant support from MSD, Pfizer, and Roche; and receives payments for lectures from MSD, AstraZeneca, Pfizer, and Kowa. Uma Kher, Manash Chatterjee, Yang Liu, Xiujiang Susie Li, Sanskruti Vaidya, Sukrut Shah, Hayes Dansky, and Yale Mitchel are employees of and have stock/stock options in Merck & Co, Inc. Jennifer Moon has no disclosures. All contributors have signed confidentiality agreements with Merck requiring that prior approval is required before publishing the research findings of the study. Publisher Copyright: {\textcopyright} The Author(s) 2014. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2014",
month = nov,
day = "11",
doi = "10.1177/1074248414529621",
language = "English (US)",
volume = "19",
pages = "543--549",
journal = "Journal of Cardiovascular Pharmacology and Therapeutics",
issn = "1074-2484",
publisher = "SAGE Publications Ltd",
number = "6",
}