Pharmacokinetics, Safety and Tolerability of Anacetrapib, a Novel Cholesteryl Ester Transfer Protein (CETP) Inhibitor, After Single and Multiple Doses in Healthy Chinese Subjects

• Published in: Advances in therapy Vol. 38; no. 7; pp. 3973 - 3985
• Main Authors: Chen, Hanjing, Chen, Weili, Li, Hui, Xu, Hongrong, Yuan, Fei, Sheng, Lei, Liu, Chao, Lin, Pingping, Yang, Mengjie, Li, Xuening, Liu, Yang, Walker, Brittany Marie, Gheyas, Ferdous, Iwamoto, Marian, Stoch, S. Aubrey, Krishna, Rajesh
• Format: Journal Article
• Language: English
• Published: Cheshire Springer Healthcare 01-07-2021
• Subjects: Cardiology; CTR; CTR20130983; Endocrinology; Internal Medicine; Medicine; Medicine & Public Health; Oncology; Original Research; Pharmacology/Toxicology; Rheumatology; Anacetrapib; CETP inhibitor; Pharmacokinetics; Race
• ISSN: 0741-238X; 1865-8652
• DOI: 10.1007/s12325-021-01794-8

Introduction
Anacetrapib is a novel, powerful cholesteryl ester transfer protein (CETP) inhibitor with bidirectional lipid regulation, which was developed for dyslipidemia. The aim of this study is to evaluate the single- and multiple-dose pharmacokinetics (PK), safety and tolerability of anacetrapib in healthy Chinese subjects and assess the PK difference between Chinese and other populations.
Methods
Forty subjects were enrolled in an open-label study consisting of three panels (50 mg single dose; 100 mg single dose followed by 100 mg once-daily multiple doses for 10 days; a 200 mg single dose). Safety and tolerability were evaluated by monitoring adverse events, laboratory safety tests, ECGs, vital signs and physical examination. PK were evaluated and compared with historical data in black and white subjects.
Results
Anacetrapib was absorbed after administration of a single oral dose, with a median
T
max
of 3.0–5.0 h and elimination half-life of 105.3–122.3 h. The AUC and
C
max
of anacetrapib increased in a slightly less than dose-proportional manner over a dose range of 50–200 mg. Once-daily administration of 100 mg of anacetrapib for 10 days resulted in a median
T
max
of 5.0 h with an apparent half-life of 193.7 h on Day 10 of multiple dosing. Anacetrapib accumulation ratios (Day 10 of multiple dosing/Day 1) were 1.39 (AUC
0–24 h
), 1.11 (
C
max
) and 2.57 (
C
24 h
).
Conclusion
The PK properties of anacetrapib in Chinese subjects are comparable to those observed in the black population and in white subjects. Single and once-daily administration of anacetrapib was generally well tolerated in healthy Chinese subjects observed in this study.
Trial Registration
chinadrugtrials.org.cn identifier number CTR20130983.