{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T18:39:18Z","timestamp":1792607958041,"version":"4.5.0"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,2,27]],"date-time":"2015-02-27T00:00:00Z","timestamp":1424995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004334","name":"Merck","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Co\u2010administration of ezetimibe with atorvastatin is a generally well\u2010tolerated treatment option that reduces <jats:styled-content style=\"fixed-case\">LDL<\/jats:styled-content>\u2010C levels and improves other lipids with greater efficacy than doubling the atorvastatin dose. The objective of the study was to demonstrate the equivalent lipid\u2010modifying efficacy of fixed\u2010dose combination (<jats:styled-content style=\"fixed-case\">FDC<\/jats:styled-content>) ezetimibe\/atorvastatin compared with the component agents co\u2010administered individually in support of regulatory filing. Two randomized, 6\u2010week, double\u2010blind cross\u2010over trials compared the lipid\u2010modifying efficacy of ezetimibe\/atorvastatin 10\/20\u00a0mg (<jats:italic>n<\/jats:italic>\u00a0=\u00a0353) or 10\/40\u00a0mg (<jats:italic>n<\/jats:italic>\u00a0=\u00a0280) vs. separate co\u2010administration of ezetimibe 10\u00a0mg plus atorvastatin 20\u00a0mg (<jats:italic>n<\/jats:italic>\u00a0=\u00a0346) or 40\u00a0mg (<jats:italic>n<\/jats:italic>\u00a0=\u00a0280), respectively, in hypercholesterolemic patients. Percent changes from baseline in <jats:styled-content style=\"fixed-case\">LDL<\/jats:styled-content>\u2010C (primary endpoint) and other lipids (secondary endpoints) were assessed by analysis of covariance; triglycerides were evaluated by longitudinal\u2010data analysis. Expected differences between <jats:styled-content style=\"fixed-case\">FDC<\/jats:styled-content> and the corresponding co\u2010administered doses were predicted from a dose\u2013response relationship model; sample size was estimated given the expected difference and equivalence margins (\u00b14%). <jats:styled-content style=\"fixed-case\">LDL<\/jats:styled-content>\u2010C\u2010lowering equivalence was based on 97.5% expanded confidence intervals (<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>) for the difference contained within the margins; equivalence margins for other lipids were not prespecified. Ezetimibe\/atorvastatin <jats:styled-content style=\"fixed-case\">FDC<\/jats:styled-content> 10\/20\u00a0mg was equivalent to co\u2010administered ezetimibe+atorvastatin 20\u00a0mg in reducing <jats:styled-content style=\"fixed-case\">LDL<\/jats:styled-content>\u2010C levels (54.0% vs. 53.8%) as was <jats:styled-content style=\"fixed-case\">FDC<\/jats:styled-content> 10\/40\u00a0mg and ezetimibe+atorvastatin 40\u00a0mg (58.9% vs. 58.7%), as predicted by the model. Changes in other lipids were consistent with equivalence (97.5% expanded <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>s &lt;\u00b13%, included 0); triglyceride changes varied more. All treatments were generally well tolerated. Hypercholesterolemic patients administered ezetimibe\/atorvastatin 10\/20 and 10\/40\u00a0mg <jats:styled-content style=\"fixed-case\">FDC<\/jats:styled-content> had equivalent <jats:styled-content style=\"fixed-case\">LDL<\/jats:styled-content>\u2010C lowering. This <jats:styled-content style=\"fixed-case\">FDC<\/jats:styled-content> formulation proved to be an efficacious and generally well\u2010tolerated lipid\u2010lowering therapy.<\/jats:p>","DOI":"10.1111\/fcp.12096","type":"journal-article","created":{"date-parts":[[2014,11,27]],"date-time":"2014-11-27T15:28:54Z","timestamp":1417102134000},"page":"209-218","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Fixed\u2010dose combination ezetimibe+atorvastatin lowers <scp>LDL<\/scp>\u2010C equivalent to co\u2010administered components in randomized trials: use of a dose\u2013response model"],"prefix":"10.1111","volume":"29","author":[{"given":"Harold E.","family":"Bays","sequence":"first","affiliation":[{"name":"Louisville Metabolic and Atherosclerosis Research Center 3288 Illinois Avenue Louisville KY 40213 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erluo","family":"Chen","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc. One Merck Drive Whitehouse Station NJ 08889 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne E.","family":"Tomassini","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc. One Merck Drive Whitehouse Station NJ 08889 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail","family":"McPeters","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc. One Merck Drive Whitehouse Station NJ 08889 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam B.","family":"Polis","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc. One Merck Drive Whitehouse Station NJ 08889 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Triscari","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc. 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