{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:32:38Z","timestamp":1791977558483,"version":"4.4.0"},"reference-count":19,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T00:00:00Z","timestamp":1730937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"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":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2025,3]]},"abstract":"Abstract<\/jats:title>\n \n Objective<\/jats:title>\n To compare the rate and extent of absorption of zavegepant 10\u2009mg (therapeutic dose) or 20\u2009mg (supratherapeutic dose) nasal spray during a migraine attack versus non\u2010migraine period, assess safety, and explore efficacy and the relationship between zavegepant concentration and therapeutic response.<\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n Physiologic changes occurring during a migraine attack could affect the pharmacokinetics of treatments for migraine.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This was a Phase 1, multicenter, open\u2010label, randomized, single\u2010dose, two\u2010period, fixed\u2010sequence, comparative bioavailability study. Participants with a history of 2\u20138 migraine attacks per month of moderate or severe pain intensity were randomized to a single dose of zavegepant 10 or 20\u2009mg, administered intranasally during a migraine attack (Period 1) and in a non\u2010migraine period (Period 2). Blood samples were collected pre\u2010dose and at pre\u2010specified intervals up to 24\u2009h post\u2010dose for plasma zavegepant concentration measurement. Safety was monitored throughout, and efficacy (migraine pain intensity score, nausea, photophobia, phonophobia, aura, and functional disability) assessed during Period 1. Plasma zavegepant pharmacokinetic parameters were calculated by standard noncompartmental methods, including maximum plasma concentration (C\n max<\/jats:sub>\n ), area under plasma concentration\u2013time curve from time zero to infinity (AUC\n 0\u2013inf<\/jats:sub>\n ), and time of C\n max<\/jats:sub>\n (T\n max<\/jats:sub>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 37 participants were evaluable for pharmacokinetics. Following administration of zavegepant 10\u2009mg, geometric mean ratios for Period 1\/Period 2 were 82.8% (90% confidence interval [CI] 60.5\u2013113.2) for C\n max<\/jats:sub>\n and 90.1% (90% CI 70.2\u2013115.5) for AUC\n 0\u2013inf<\/jats:sub>\n . Following administration of zavegepant 20\u2009mg, geometric mean ratios for Period 1\/Period 2 were 72.5% (90% CI 57.9\u201390.8) for C\n max<\/jats:sub>\n and 73.4% (90% CI 58.8\u201391.7) for AUC\n 0\u2013inf<\/jats:sub>\n . Averaging over the study period, geometric mean ratios for zavegepant 20\u2009mg\/10\u2009mg were 142.5% (90% CI 118.6\u2013171.4) for C\n max<\/jats:sub>\n and 157.0% (90% CI 133.6\u2013184.5) for AUC\n 0\u2013inf<\/jats:sub>\n . Median T\n max<\/jats:sub>\n was 0.5\u2009h for both doses regardless of Period. Zavegepant was well tolerated in both study periods and effective during Period 1 at both dose levels. There was no apparent correlation between concentration at 0.5\u2009h or 2\u2009h post\u2010dose and efficacy outcomes.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Zavegepant exposure was comparable during a migraine attack and a non\u2010migraine period, particularly at the therapeutic dose of 10\u2009mg. When averaging over migraine and non\u2010migraine periods, there was a less\u2010than\u2010dose proportional increase in zavegepant exposure when the dose was doubled from 10 to 20\u2009mg. The median T\n max<\/jats:sub>\n was 0.5\u2009h regardless of migraine attack or dose. Zavegepant 10 and 20\u2009mg exhibited favorable safety profiles during migraine attacks and non\u2010migraine periods, and were effective to relieve pain, associated symptoms, and functional disability during migraine attacks, with no apparent correlation between zavegepant concentration and efficacy outcomes.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/head.14856","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T07:24:17Z","timestamp":1730964257000},"page":"484-494","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Comparative bioavailability of single\u2010dose zavegepant during and between migraine attacks: A phase 1, randomized, open\u2010label, fixed\u2010sequence, two\u2010period study"],"prefix":"10.1111","volume":"65","author":[{"given":"Richard J.","family":"Bertz","sequence":"first","affiliation":[{"name":"Biohaven Pharmaceuticals Inc. New\u00a0Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie L.","family":"Collins","sequence":"additional","affiliation":[{"name":"Pfizer Inc. Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Madonia","sequence":"additional","affiliation":[{"name":"Biohaven Pharmaceuticals Inc. New\u00a0Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajinder","family":"Bhardwaj","sequence":"additional","affiliation":[{"name":"Certara USA Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Kamen","sequence":"additional","affiliation":[{"name":"Biohaven Pharmaceuticals Inc. New\u00a0Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle T.","family":"Matschke","sequence":"additional","affiliation":[{"name":"Pfizer Inc. Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Liu","sequence":"additional","affiliation":[{"name":"Pfizer Inc. Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,7]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2007.00922.x"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.12112"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.14099"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2012.02292.x"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.1995.hed3507387.x"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.14153"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-021-00509-5"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-023-01662-6"},{"key":"e_1_2_12_10_1","volume-title":"Zavzpret (Zavegepant) Nasal Spray Prescribing Information","author":"Pfizer Labs","year":"2023"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.14389"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(22)00517-8"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102413512031"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.12973"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102414527014"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/SCS.0b013e31827c80b1"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102417738202"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1526-4610.1999.3904264.x"},{"key":"e_1_2_12_19_1","volume-title":"Zavzpret Office of Clinical Pharmacology Integrated Review","author":"Food and Drug Administration","year":"2022"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.98.18_supplement.1003"}],"container-title":["Headache: The Journal of Head and Face Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/headachejournal.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/head.14856","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T09:03:31Z","timestamp":1762074211000},"score":1,"resource":{"primary":{"URL":"https:\/\/headachejournal.onlinelibrary.wiley.com\/doi\/10.1111\/head.14856"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,7]]},"references-count":19,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1111\/head.14856"],"URL":"https:\/\/doi.org\/10.1111\/head.14856","archive":["Portico"],"relation":{},"ISSN":["0017-8748","1526-4610"],"issn-type":[{"value":"0017-8748","type":"print"},{"value":"1526-4610","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,7]]},"assertion":[{"value":"2024-04-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}