{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:11:17Z","timestamp":1792059077293,"version":"4.4.0"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T00:00:00Z","timestamp":1665705600000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Evaluate the efficacy, safety, and tolerability of zavegepant nasal spray in the acute treatment of migraine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Calcitonin gene\u2010related peptide\u2010targeting agents are a novel class of therapeutics for migraine, but none are currently available as a nonoral option for acute treatment. Zavegepant, a high\u2010affinity, selective, and structurally unique calcitonin gene\u2010related peptide\u2010receptor antagonist in late\u2010stage development, is formulated as a nasal spray for the acute treatment of migraine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This randomized, dose\u2010ranging, placebo\u2010controlled, Phase 2\/3 trial in adults aged \u226518\u2009years with migraine (NCT03872453) was conducted at US study sites. Participants were randomized by an interactive web response system and treated a single attack of moderate to severe pain intensity with zavegepant nasal spray 5, 10, 20\u2009mg, or placebo. Coprimary efficacy endpoints were pain freedom and freedom from the most bothersome symptom at 2\u00a0h postdose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of the 1673 participants aged 18 to 79\u2009years who were randomized, 1588 were treated with study medication, and 1581 (mean age 40.8\u2009years, 85.5% female) were analyzed for efficacy: zavegepant 5\u00a0mg (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0387), 10\u00a0mg (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0391), 20\u2009mg (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0402), and placebo (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0401). Zavegepant 10 and 20\u2009mg were more effective than placebo on the coprimary endpoints of pain freedom at 2\u00a0h postdose (placebo: 15.5% [98.3% confidence interval (CI), 11.1, 19.8]; 10\u00a0mg: 22.5% [98.3% CI, 17.5, 27.6;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.0113]; 20\u2009mg: 23.1% [98.3% CI, 18.1, 28.2;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.0055]) and freedom from the most bothersome symptom at 2\u00a0h postdose (placebo: 33.7% [98.3% CI, 28.0, 39.3]; 10\u00a0mg: 41.9% [98.3% CI, 36.0, 47.9;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.0155]; 20\u2009mg: 42.5% [98.3% CI, 36.6, 48.4;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.0094]). Findings for the 5\u00a0mg dose were not significant. The most common treatment\u2010emergent adverse events with zavegepant 10 and 20\u2009mg and placebo were dysgeusia (13.5% to 16.1% vs. 3.5%), nausea (2.7% to 4.1% vs. 0.5%), and nasal discomfort (1.3% to 5.2% vs. 0.2%). Most adverse events were mild or moderate and resolved without treatment. There was no signal of hepatotoxicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Zavegepant nasal spray, in single doses of 10 or 20\u2009mg, was effective for the acute treatment of migraine, with a favorable safety profile. Additional research is needed to confirm its potential as a nonoral medication for the acute treatment of migraine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.14389","type":"journal-article","created":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T03:28:37Z","timestamp":1665718117000},"page":"1153-1163","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":100,"title":["Zavegepant nasal spray for the acute treatment of migraine: A Phase 2\/3 double\u2010blind, randomized, placebo\u2010controlled, dose\u2010ranging trial"],"prefix":"10.1111","volume":"62","author":[{"given":"Robert","family":"Croop","sequence":"first","affiliation":[{"name":"Research and Development Biohaven Pharmaceuticals, Inc.  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Madonia","sequence":"additional","affiliation":[{"name":"Research and Development Biohaven Pharmaceuticals, Inc.  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Stock","sequence":"additional","affiliation":[{"name":"Research and Development Biohaven Pharmaceuticals, Inc.  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Thiry","sequence":"additional","affiliation":[{"name":"Research and Development Biohaven Pharmaceuticals, Inc.  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micaela","family":"Forshaw","sequence":"additional","affiliation":[{"name":"Research and Development Biohaven Pharmaceuticals, Inc.  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New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard B.","family":"Lipton","sequence":"additional","affiliation":[{"name":"Neurology, Epidemiology and Population Health, and Psychiatry and Behavioral Sciences Albert Einstein College of Medicine  Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,10,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.12499"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.13407"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.55.6.754"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.14153"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1526-4610.2002.0420s1003.x"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0098933"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.13588"},{"key":"e_1_2_11_9_1","article-title":"Sumatriptan (all routes of administration) for acute migraine attacks in adults \u2010 overview of Cochrane reviews","volume":"2014","author":"Derry CJ","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.13165"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)06711-3"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.12962"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.13179"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-1241.2000.tb11905.x"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-013-0061-2"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.13700"},{"key":"e_1_2_11_17_1","unstructured":"Dihydroergotamine mesylate nasal spray prescribing information.2019. 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