{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T18:17:00Z","timestamp":1773080220386,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T00:00:00Z","timestamp":1606176000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009947","name":"Merck Sharp and Dohme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009947","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004334","name":"Merck","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:p>Atogepant is a potent, selective, oral calcitonin gene\u2013related peptide (CGRP) receptor antagonist in development for migraine prevention. The chemical structure of atogepant is distinct from previous CGRP receptor antagonists, which were associated with elevated serum alanine aminotransferase (ALT) in clinical trials. Here, we report the safety, tolerability, and pharmacokinetics (PKs) of a once\u2010daily supratherapeutic dose (170\u00a0mg) of atogepant for 28\u00a0days from a randomized, double\u2010blind, placebo\u2010controlled phase I trial in healthy participants. Overall safety, hepatic safety, and plasma PK parameters were evaluated. Thirty\u2010four participants aged 23\u201355\u00a0years enrolled; 28 (82.4%) completed the study in accordance with the protocol. Multiple doses of 170\u00a0mg atogepant for 28 consecutive days were generally well\u2010tolerated. All adverse events (AEs; reported in 87.0% of the atogepant group; 72.7%, placebo) were mild in severity except one serious AE of subarachnoid hemorrhage due to a bicycle accident and not considered related to treatment. There were two discontinuations due to AEs, both with atogepant, one considered possibly related to treatment. Over 28\u00a0days of treatment, no participant receiving atogepant had an ALT elevation above 1.5\u00a0\u00d7\u00a0upper limit of normal. Change from baseline in serum ALT levels was not different between atogepant and placebo. Atogepant is rapidly absorbed (median time to maximum plasma concentration, ~\u00a02\u00a0hours) with an apparent terminal half\u2010life of ~\u00a011\u00a0hours, and no evidence of accumulation after once\u2010daily dosing. Overall, atogepant at a high oral dose is safe and well\u2010tolerated in healthy participants with no clinically meaningful elevations in ALT.<\/jats:p>","DOI":"10.1111\/cts.12917","type":"journal-article","created":{"date-parts":[[2020,11,3]],"date-time":"2020-11-03T19:16:15Z","timestamp":1604430975000},"page":"599-605","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Atogepant Is Not Associated With Clinically Meaningful Alanine Aminotransferase Elevations in Healthy Adults"],"prefix":"10.1111","volume":"14","author":[{"given":"K. Chris","family":"Min","sequence":"first","affiliation":[{"name":"Formerly of Merck &amp; Co., Inc. Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter K.","family":"Kraft","sequence":"additional","affiliation":[{"name":"Thomas Jefferson University Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phung","family":"Bondiskey","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc. Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francheska","family":"Col\u00f3n\u2010Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc. Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Liu","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc. Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jialin","family":"Xu","sequence":"additional","affiliation":[{"name":"Formerly of Merck &amp; Co., Inc. 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Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramesh","family":"Boinpally","sequence":"additional","affiliation":[{"name":"AbbVie Madison New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,11,24]]},"reference":[{"key":"e_1_2_11_1_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-030212-183717"},{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2019.06.001"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32154-2"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-018-0846-2"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000252808.97649.21"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.12878"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.13613"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32504-8"},{"key":"e_1_2_11_9_1","volume-title":"Ubrelvy [package insert]","year":"2020"},{"key":"e_1_2_11_10_1","volume-title":"Nurtec ODT [package insert]","year":"2020"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102416653233"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102413500727"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1811090"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1813049"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.16711"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.13510"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30234-9"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000286940.29755.61"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61626-8"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181b87942"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000771"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102415584308"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102411398399"},{"key":"e_1_2_11_24_1","unstructured":"Merck updates status of clinical development programs for investigational CGRP receptor antagonist treatments for acute migraine; MK\u20103207 clinical development discontinued [press release]. BusinessWire 2009. <https:\/\/www.businesswire.com\/news\/home\/20090910005709\/en\/Merck\u2010Updates\u2010Status\u2010Clinical\u2010Development\u2010Programs\u2010Investigational>. 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