First-in-human data: TA-8995 (obicetrapib) blocks 92-99% of CETP activity and is well tolerated across 1 to 150mg doses (Br J Clin Pharmacol 2014)

Original title: Tolerability, pharmacokinetics and pharmacodynamics of TA-8995, a selective cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects

Br J Clin Pharmacol · 1 September 2014 · 6

Ford J, Lawson M, Fowler D, Maruyama N, Mito S, Tomiyasu K, Kinoshita S, Suzuki C, Kawaguchi A, Round P, Boyce M, Warrington S et al.

Two double-blind, randomised phase 1 studies characterised the tolerability, pharmacokinetics and pharmacodynamics of oral TA-8995 (obicetrapib) in healthy subjects, including single doses from 5 to 150 mg and repeated once-daily doses of 1 to 25 mg for 21 to 28 days in Caucasian and Japanese participants. Peak concentrations occurred about 4 hours post-dose, mean half-lives ranged from 81 to 166 hours without a clear dose relationship, and the drug was not excreted in urine. At 2.5 to 25 mg once daily, TA-8995 nearly completely inhibited CETP activity (92 to 99%), raised HDL-C by 96 to 140% and lowered LDL-C by 40 to 53%, with dose-related increases in apoA-1, apoE, HDL2-C and HDL3-C, and decreases in apoB and Lp(a). No significant effects of age, sex, ethnicity or food were seen, and all doses were well tolerated. The first-in-human data establishing TA-8995 as a potent CETP inhibitor warranting further development.

Original abstract

Aims: Two double-blind, randomized studies were conducted to assess the tolerability, pharmacokinetics and pharmacodynamics of oral TA-8995, a new cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects.

Methods: Study 1: Subjects received single doses of TA-8995 or placebo (fasted). Doses were 5, 10, 25, 50 (fed/fasted), 100 and 150 mg (Caucasian males, 18-55 years), 25 mg (Caucasian males, > 65 years and Caucasian females, 18-55 years), 25, 50, 100 and 150 mg (Japanese males, 18-55 years). Study 2: Caucasian males (18-55 years) received 1, 2.5, 10 or 25 mg once daily TA-8995 or placebo for 21-28 days. Blood and urine for pharmacokinetics and/or pharmacodynamics were collected. Tolerability was assessed by adverse events, vital signs, electrocardiograms and laboratory safety tests.

Results: Peak TA-8995 concentrations occurred approximately 4 h post-dose. Mean half-lives ranged from 81 to 166 h, without an obvious dose relationship. Exposure increased less than proportionally to dose. TA-8995 was not excreted in urine. Following 2.5 to 25 mg once daily dosing, TA-8995 demonstrated nearly complete inhibition of CETP activity (92-99%), increased high density lipoprotein-cholesterol (HDL-C) by 96 to 140% and decreased low density liporotein-cholesterol (LDL-C) by 40% to 53%. There were dose-related increases in apolipoproteins A-1 and E, HDL2-C and HDL3-C, and decreases in apolipoprotein B and lipoprotein A. There was no evidence of significant effects of age, gender, ethnicity or food on pharmacokinetics or pharmacodynamics. All doses were well tolerated.

Conclusions: TA-8995 is a potent CETP inhibitor and warrants further investigation.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.