{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:50:53Z","timestamp":1792605053813,"version":"4.5.0"},"reference-count":38,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cephalalgia"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>A subset of individuals with migraine are unsuitable for triptans due to intolerance, lack of efficacy, or contraindications. This phase 4 study assessed the efficacy and tolerability of a single 75-mg dose of rimegepant orally disintegrating tablet (ODT) for acute treatment of migraine in adults with documented triptan unsuitability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Participants (aged \u226518 years with 4\u201314 migraine days per month) with documented history of (A) intolerance and\/or lack of efficacy to \u22652 triptans or (B) contraindication to triptans were randomized (1:1) to rimegepant 75\u2005mg ODT or placebo to treat a single migraine attack of moderate or severe pain intensity. Randomization was stratified by history of clinically relevant cardiovascular disease. The primary endpoint was the percentage of participants with migraine pain relief (no or mild pain) at 2\u2005h post dose. Key secondary endpoints, tested using a hierarchal approach to control type 1 error, included the percentage of participants with migraine pain freedom at 2\u2005h, rescue medication use within 24\u2005h, return to normal function at 2\u2005h, sustained return to normal function from 2\u201324\u2005h and from 2\u201348\u2005h, sustained migraine pain relief from 2\u201324\u2005h and from 2\u201348\u2005h, sustained migraine pain freedom from 2\u201324\u2005h and from 2\u201348\u2005h, and most bothersome symptom freedom at 2\u2005h. Safety was assessed via adverse events (AEs) and laboratory tests.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overall, 585 participants (89.1% were female, mean age was 42.9 years) received study medication (rimegepant,\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u2009295; placebo,\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u2009290). Participants analyzed for efficacy (rimegepant,\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u2009286; placebo,\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u2009284) had documented failure to \u22652 triptans with \u22651 reason due to prior intolerance (30.5%) and\/or \u22651 reason due to lack of efficacy (84.9%); 9.1% had a contraindication. Rimegepant demonstrated superiority over placebo for the primary endpoint of migraine pain relief at 2\u2005h (55.9% vs 32.7%; difference [95% CI]: 23.2% [15.3\u201331.1%];\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) and all 10 alpha-protected key secondary endpoints including pain freedom at 2\u2005h (all\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009\u2264\u20090.0005). AE rates were similar across treatments (12.5% vs 12.1%), with no severe AEs, serious AEs, or clinically significant laboratory test abnormalities reported in the rimegepant group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A single 75-mg dose of rimegepant ODT was efficacious and well tolerated for acute treatment of migraine in adults unsuitable for triptans. This first prospective trial of a gepant in this population supports calcitonin gene-related peptide antagonism as a valuable option when triptans are unsuitable.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>Clinicaltrials.gov NCT05509400.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03331024251395298","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T07:56:33Z","timestamp":1763538993000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["Rimegepant for acute treatment of migraine in triptan-unsuitable adults: A randomized, double-blind, placebo-controlled phase 4 trial"],"prefix":"10.1177","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0951-5804","authenticated-orcid":false,"given":"Messoud","family":"Ashina","sequence":"first","affiliation":[{"name":"Department of Neurology, Danish Headache Center, Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4965-7700","authenticated-orcid":false,"given":"Peter","family":"McAllister","sequence":"additional","affiliation":[{"name":"New England Institute for Neurology and Headache, Stamford, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9362-3711","authenticated-orcid":false,"given":"Charly","family":"Gaul","sequence":"additional","affiliation":[{"name":"Headache Center Frankfurt, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8774-1407","authenticated-orcid":false,"given":"Adolfo","family":"Leyva-Rendon","sequence":"additional","affiliation":[{"name":"National Institute of Neurology and Neurosurgery"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luz M.","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Pfizer Inc"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2932-0115","authenticated-orcid":false,"given":"Catherine","family":"Nalpas","sequence":"additional","affiliation":[{"name":"Pfizer Inc"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Thiry","sequence":"additional","affiliation":[{"name":"Pfizer Inc"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1648-8621","authenticated-orcid":false,"given":"Lucy","family":"Abraham","sequence":"additional","affiliation":[{"name":"Pfizer R&D UK Ltd"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4105-1248","authenticated-orcid":false,"given":"Robert J.","family":"Fountaine","sequence":"additional","affiliation":[{"name":"Pfizer Inc"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terence","family":"Fullerton","sequence":"additional","affiliation":[{"name":"Pfizer Inc"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/03331024241252666"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/head.14854"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40122-020-00223-y"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-020-01110-9"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-023-01676-0"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/head.12820"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/head.12198"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2012.12.020"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40120-021-00304-w"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/head.12962"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1177\/2150132720963680"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32504-8"},{"key":"e_1_3_3_14_2","unstructured":"US Food and Drug Administration. 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