John J P Kastelein, Marc Ditmarsch, Andrew Hsieh, Douglas Kling, Ashley Walker, Mary R Dicklin, Zia Tayab, Mohammed Bouhajib, Michael H Davidson
{"title":"一项药物-药物相互作用研究评估奥比西布治疗对健康志愿者阿托伐他汀或瑞舒伐他汀水平的药代动力学影响。","authors":"John J P Kastelein, Marc Ditmarsch, Andrew Hsieh, Douglas Kling, Ashley Walker, Mary R Dicklin, Zia Tayab, Mohammed Bouhajib, Michael H Davidson","doi":"10.1007/s40256-025-00740-1","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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>t</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>t</sub> (p = 0.0026) and AUC<sub>inf</sub> (p = 0.0012), the differences were small (9-10%) and not deemed clinically important. Overall, all study drugs were safe and well tolerated.</p><p><strong>Conclusions: </strong>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><p><strong>Clinical trial registration: </strong>NCT06081166.</p>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":" ","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A Drug-Drug Interaction Study Evaluating the Pharmacokinetic Consequences of Obicetrapib Therapy on Atorvastatin or Rosuvastatin Levels in Healthy Volunteers.\",\"authors\":\"John J P Kastelein, Marc Ditmarsch, Andrew Hsieh, Douglas Kling, Ashley Walker, Mary R Dicklin, Zia Tayab, Mohammed Bouhajib, Michael H Davidson\",\"doi\":\"10.1007/s40256-025-00740-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>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><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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>t</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>t</sub> (p = 0.0026) and AUC<sub>inf</sub> (p = 0.0012), the differences were small (9-10%) and not deemed clinically important. 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A Drug-Drug Interaction Study Evaluating the Pharmacokinetic Consequences of Obicetrapib Therapy on Atorvastatin or Rosuvastatin Levels in Healthy Volunteers.
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.
期刊介绍：
Promoting rational therapy within the discipline of cardiology, the American Journal of Cardiovascular Drugs covers all aspects of the treatment of cardiovascular disorders, particularly the place in therapy of newer and established agents.
Via a program of reviews and original clinical research articles, the journal addresses major issues relating to treatment of these disorders, including the pharmacology, efficacy and adverse effects of the major classes of drugs; information on newly developed drugs and drug classes; the therapeutic implications of latest research into the aetiology of cardiovascular disorders; and the practical management of specific clinical situations.
The American Journal of Cardiovascular Drugs offers a range of additional enhanced features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by a Key Points summary, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist patients, caregivers and others in understanding important medical advances. The journal also provides the option to include various other types of enhanced features including slide sets, videos and animations. All enhanced features are peer reviewed to the same high standard as the article itself. Peer review is conducted using Editorial Manager®, supported by a database of international experts. This database is shared with other Adis journals.
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