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Objective <p>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. </p> Methods <p>An open-label study was conducted to evaluate the PK of atorvastatin 80&#xa0;mg (cohort 1, <i>n</i>&#xa0;=&#xa0;42) or rosuvastatin 40&#xa0;mg (cohort 2, <i>n</i>&#xa0;=&#xa0;32, non-Asians) with and without co-administration of 10&#xa0;mg obicetrapib in healthy adult males and females. Study participants received statin on day −&#xa0;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.</p> Results <p>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 (AUC<sub><i>t</i></sub>) and from time 0 to infinity (AUC<sub>inf</sub>) 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 AUC<sub><i>t</i></sub> (<i>p</i>&#xa0;=&#xa0;0.0026) and AUC<sub>inf</sub> (<i>p</i>&#xa0;=&#xa0;0.0012), the differences were small (9–10%) and not deemed clinically important. Overall, all study drugs were safe and well tolerated.</p> Conclusions <p>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.</p> Clinical Trial Registration <p>NCT06081166.</p>

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A Drug–Drug Interaction Study Evaluating the Pharmacokinetic Consequences of Obicetrapib Therapy on Atorvastatin or Rosuvastatin Levels in Healthy Volunteers

  • 期刊论文

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  • 发表日期：

    2025年6月26日

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  • John J. P. Kastelein,
  • Marc Ditmarsch,
  • Andrew Hsieh,
  • Douglas Kling,
  • Ashley Walker,
  • Mary R. Dicklin,
  • Zia Tayab,
  • Mohammed Bouhajib,
  • Michael H. Davidson

摘要

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.