Obicetrapib as an Adjunct to Stable Statin Therapy in Japanese Subjects: Results from a Randomized Phase 2 Trial

• Published in: Journal of Atherosclerosis and Thrombosis Vol. 31; no. 10; pp. 1386 - 1397
• Main Authors: Kuroyanagi, Satoshi, Dicklin, Mary R, Nakata, Akitaka, Harada-Shiba, Mariko, Hsieh, Andrew, Wuerdeman, Erin, Nield, Annie, Ditmarsch, Marc, Davdison, Michael H, Kling, Douglas, Sueyoshi, Atsushi, Kastelein, John J.P.
• Format: Journal Article
• Language: English
• Published: Japan Japan Atherosclerosis Society 01.10.2024
• Subjects: Aged; Anticholesteremic Agents - administration & dosage; Anticholesteremic Agents - therapeutic use; Cholesterol Ester Transfer Proteins - antagonists & inhibitors; Cholesterol, LDL - blood; Cholesteryl ester transfer protein; Double-Blind Method; Drug Therapy, Combination; Dyslipidemia; East Asian People; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Japan; Japanese; Male; Middle Aged; Obicetrapib; Original; Statin; Japan; Statin; Obicetrapib; Japanese; Cholesteryl ester transfer protein; Dyslipidemia
• ISSN: 1340-3478; 1880-3873; 1880-3873
• DOI: 10.5551/jat.64828

Aims: Obicetrapib is a highly selective cholesteryl ester transfer protein (CETP) inhibitor shown to reduce low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB), when taken as monotherapy and in combination with ezetimibe on a background of statins, in clinical trials predominantly conducted in Northern European/Caucasian participants. We characterized the efficacy, safety, and tolerability of obicetrapib within an Asian-Pacific region population.Methods: This double-blind, randomized, phase 2 trial examined obicetrapib 2.5, 5, and 10 mg/d, compared with placebo, for 8 weeks as an adjunct to stable statin therapy (atorvastatin 10 or 20 mg/d or rosuvastatin 5 or 10 mg/d) in Japanese men and women who had not achieved 2022 Japan Atherosclerosis Society Guidelines and had LDL-C ＞70 mg/dL or non-high-density lipoprotein cholesterol (non-HDL-C) ＞100 mg/dL and triglycerides (TG) ＜400 mg/dL. Endpoints included LDL-C, non-HDL-C, HDL-C, very low-density lipoprotein cholesterol, apolipoproteins, TG, steady state pharmacokinetics (PK) in obicetrapib arms, safety, and tolerability.Results: In the 102 randomized subjects (mean age 64.8 y, 71.6% male), obicetrapib significantly lowered median LDL-C, apoB, and non-HDL-C, and raised HDL-C at all doses; responses in the obicetrapib 10 mg group were -45.8%, -29.7%, -37.0%, and +159%, respectively (all p＜0.0001 vs. placebo). The PK profile demonstrated near complete elimination of drug by 4 weeks. Obicetrapib was well tolerated and there were no adverse safety signals.Conclusions: All doses of obicetrapib taken as an adjunct to stable statin therapy significantly lowered atherogenic lipoprotein lipid parameters, showed near complete elimination of drug by 4 weeks, and were safe and well tolerated in a Japanese population, similar to previous studies of obicetrapib conducted in predominantly Caucasian participants.