{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T13:56:35Z","timestamp":1784296595176,"version":"3.55.0"},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T00:00:00Z","timestamp":1708041600000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Co\u2010administration of clesacostat (acetyl\u2010CoA carboxylase inhibitor, PF\u201005221304) and ervogastat (diacylglycerol O\u2010acyltransferase inhibitor, PF\u201006865571) in laboratory models improved non\u2010alcoholic fatty liver disease (NAFLD)\/non\u2010alcoholic steatohepatitis (NASH) end points and mitigated clesacostat\u2010induced elevations in circulating triglycerides. Clesacostat is cleared via organic anion\u2010transporting polypeptide\u2010mediated hepatic uptake and cytochrome P450 family 3A (CYP3A); in\u00a0vitro clesacostat is identified as a potential CYP3A time\u2010dependent inactivator. In\u00a0vitro ervogastat is identified as a substrate and potential inducer of CYP3A. Prior to longer\u2010term efficacy trials in participants with NAFLD, safety and pharmacokinetics (PK) were evaluated in a phase I, non\u2010randomized, open\u2010label, fixed\u2010sequence trial in healthy participants. In Cohort 1, participants (<jats:italic>n<\/jats:italic>\u2009=\u20097) received clesacostat 15\u2009mg twice daily (b.i.d.) alone (Days 1\u20137) and co\u2010administered with ervogastat 300\u2009mg b.i.d. (Days 8\u201314). Mean systemic clesacostat exposures, when co\u2010administered with ervogastat, decreased by 12% and 19%, based on maximum plasma drug concentration and area under the plasma drug concentration\u2013time curve during the dosing interval, respectively. In Cohort 2, participants (<jats:italic>n<\/jats:italic>\u2009=\u20099) received ervogastat 300\u2009mg b.i.d. alone (Days 1\u20137) and co\u2010administered with clesacostat 15\u2009mg b.i.d. (Days 8\u201314). There were no meaningful differences in systemic ervogastat exposures when administered alone or with clesacostat. Clesacostat 15\u2009mg b.i.d. and ervogastat 300\u2009mg b.i.d. co\u2010administration was overall safe and well tolerated in healthy participants. Cumulative safety and no clinically meaningful PK drug interactions observed in this study supported co\u2010administration of these two novel agents in additional studies exploring efficacy and safety in the management of NAFLD.<\/jats:p>","DOI":"10.1111\/cts.13687","type":"journal-article","created":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T10:31:43Z","timestamp":1708079503000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Investigation of pharmacokinetic drug interaction between clesacostat and <scp>DGAT2<\/scp> inhibitor ervogastat in healthy adult participants"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3749-5222","authenticated-orcid":false,"given":"Aarti","family":"Sawant\u2010Basak","sequence":"first","affiliation":[{"name":"Clinical Pharmacology, Early Clinical Development Worldwide Research, Development and Medical, Pfizer Inc.  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Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6577-5657","authenticated-orcid":false,"given":"Roberto A.","family":"Calle","sequence":"additional","affiliation":[{"name":"Internal Medicine Research Unit Worldwide Research, Development and Medical, Pfizer Inc.  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