{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T21:23:03Z","timestamp":1768598583578,"version":"3.49.0"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"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":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This work aimed to develop an appropriate model to evaluate the exposure\u2013response relationship (ERR) for monthly migraine days (MMD) in atogepant's key migraine prevention clinical trials to support dose selection. The ERR between atogepant concentration and MMD over time was analyzed utilizing data from one phase 2b\/3 and three phase 3 studies in patients with episodic or chronic migraine (EM\/CM). Several distribution models were evaluated for placebo data, whereas two modified normal distributions were introduced enabling bounded MMD modeling. Exposure metrics and shapes for ERR were tested for the most suitable distribution. Stepwise covariate search, visual predictive checks, and plots of model\u2010predicted MMD over the range of exposure metrics were utilized in model development, evaluation, and selection. The final MMD exposure\u2013response model was able to model patients with EM\/CM simultaneously and was based on a modified normal distribution with\n                    <jats:italic>E<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    ERR on\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>min<\/jats:sub>\n                    . The model adequately described the observed data over time. Due to the\n                    <jats:italic>E<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    relationship, MMD at Week 9\u201312 plateaued around their model\u2010based atogepant\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>min<\/jats:sub>\n                    \u2010EC\n                    <jats:sub>90<\/jats:sub>\n                    of 3.71\u2009nM, which is similar to most\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>min<\/jats:sub>\n                    exposures seen at the 10\u2009mg once\u2010daily regimen. All approved atogepant dosages for EM\/CM achieve effective concentrations to inhibit the calcitonin gene\u2010peptide receptor by 90%. Patients who have been failed by conventional oral migraine preventive treatments or patients with a higher baseline MMD may require a longer treatment period to reach atogepant's maximal effect. No significant difference in efficacy was evident in patients exposed to prior oral migraine preventives compared to treatment\u2010na\u00efve patients.\n                  <\/jats:p>","DOI":"10.1002\/psp4.70154","type":"journal-article","created":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T05:40:31Z","timestamp":1763790031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exposure\u2013Response Modeling of Monthly Migraine Days for Efficacy of Atogepant in Patients With Episodic or Chronic Migraine"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5822-4246","authenticated-orcid":false,"given":"Louisa","family":"Schlachter","sequence":"first","affiliation":[{"name":"Clinical Pharmacology AbbVie Deutschland GmbH &amp; Co. KG  Ludwigshafen am Rhein Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2730-6988","authenticated-orcid":false,"given":"Denise","family":"Beck","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie Deutschland GmbH &amp; Co. KG  Ludwigshafen am Rhein Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8267-9210","authenticated-orcid":false,"given":"Ramesh R.","family":"Boinpally","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7986-4447","authenticated-orcid":false,"given":"Sven","family":"Stodtmann","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie Deutschland GmbH &amp; Co. KG  Ludwigshafen am Rhein Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(24)00038\u20103"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102417738202"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.13456"},{"key":"e_1_2_9_5_1","volume-title":"QULIPTA (Atogepant) [Package Insert]","author":"AbbVie","year":"2023"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.14439"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194\u2010024\u201001783\u20106"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/03331024221128250"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13707"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2023.2280221"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.916"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40120\u2010024\u201000699\u20102"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(24)00025\u20105"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(20)30234\u20109"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2035908"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(23)01049\u20108"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102411417901"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.567"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.13845"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40273\u2010023\u201001288\u20101"},{"key":"e_1_2_9_21_1","doi-asserted-by":"crossref","unstructured":"L.Schlachter S.Stodtmann A.Voelkner F.Jonsson H. M.Lagraauw andR. R.Boinpally \u201cPopulation Pharmacokinetics of Atogepant for the Prevention of Migraine \u201d Submitted to Clinical Pharmacokinetics (2025).","DOI":"10.1007\/s40262-025-01566-5"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1012299115260"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.4310\/SII.2018.v11.n2.a11"},{"key":"e_1_2_9_24_1","unstructured":"J.RogersandJ.French \u201cAn Extension of Beta Regression to Handle Scores at Boundaries \u201d Metrum Research Group (2021) https:\/\/www.metrumrg.com\/wp\u2010content\/uploads\/2021\/06\/BetaRegression\u2010MetrumRG\u2010Rogers\u2010French.pdf."},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.131"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12015"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12838"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/25158163231191582"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1017\/pan.2022.20"}],"container-title":["CPT: Pharmacometrics &amp; Systems Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.70154","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/psp4.70154","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.70154","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T09:47:36Z","timestamp":1768556856000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/psp4.70154"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,21]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/psp4.70154"],"URL":"https:\/\/doi.org\/10.1002\/psp4.70154","archive":["Portico"],"relation":{},"ISSN":["2163-8306","2163-8306"],"issn-type":[{"value":"2163-8306","type":"print"},{"value":"2163-8306","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,21]]},"assertion":[{"value":"2025-08-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70154"}}