Drug-drug interaction study finds no clinically meaningful effect of obicetrapib on atorvastatin or rosuvastatin exposure in healthy volunteers (Am J Cardiovasc Drugs 2025)

Original title: A Drug-Drug Interaction Study Evaluating the Pharmacokinetic Consequences of Obicetrapib Therapy on Atorvastatin or Rosuvastatin Levels in Healthy Volunteers

Am J Cardiovasc Drugs · 26 June 2025 · 6

Kastelein JJP, Ditmarsch M, Hsieh A, Kling D, Walker A, Dicklin MR, Tayab Z, Bouhajib M, Davidson MH

An open-label pharmacokinetic study in healthy adults evaluated whether obicetrapib affects statin exposure, dosing atorvastatin 80 mg (cohort 1, n = 42) or rosuvastatin 40 mg (cohort 2, n = 32, non-Asian) alone and co-administered with obicetrapib 10 mg. The 90% confidence intervals for maximum plasma concentration and area under the curve for both statins with obicetrapib fell within the pre-specified bioequivalence range (80.00 to 125.00%) versus statin alone. Atorvastatin area-under-curve measures showed statistically significant but small differences (9 to 10%, P = 0.0026 and P = 0.0012) not considered clinically important. All study drugs were safe and well tolerated. Supports co-administering obicetrapib with high-intensity statins without dose adjustment. Registered as NCT06081166.

Original abstract

Objective: Obicetrapib, a selective cholesteryl ester transfer protein inhibitor in development for the treatment of dyslipidemia and cardiovascular risk, is expected to be administered with high-intensity statins in clinical practice. This study was performed to assess the effect of obicetrapib on the pharmacokinetics (PK) of atorvastatin and rosuvastatin.

Methods: An open-label study was conducted to evaluate the PK of atorvastatin 80 mg (cohort 1, n = 42) or rosuvastatin 40 mg (cohort 2, n = 32, non-Asians) with and without co-administration of 10 mg obicetrapib in healthy adult males and females. Study participants received statin on day - 4, obicetrapib on days 1-11, statin co-administered with obicetrapib on day 12, and obicetrapib on days 13-17. Blood samples were collected throughout the dosing period and analyzed for plasma obicetrapib (both cohorts); atorvastatin, ortho-hydroxy atorvastatin, and para-hydroxy atorvastatin (cohort 1), and rosuvastatin (cohort 2). Safety and tolerability were also assessed.

Results: The 90% confidence intervals of the geometric mean ratios for the log-transformed maximum plasma concentration and area under the curve from time 0 to the time of the last measurable concentration (AUCt) and from time 0 to infinity (AUCinf) for atorvastatin and rosuvastatin were all within the range pre-specified for bioequivalence (80.00-125.00%) of statin plus obicetrapib versus statin alone. Although there were significant treatment effects for atorvastatin AUCt (p = 0.0026) and AUCinf (p = 0.0012), the differences were small (9-10%) and not deemed clinically important. Overall, all study drugs were safe and well tolerated.

Conclusions: No clinically significant PK interaction occurred between multiple daily doses of obicetrapib on the single-dose PK of either atorvastatin or rosuvastatin in healthy volunteers.

Clinical Trial Registration: NCT06081166.

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