{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:59:28Z","timestamp":1790679568611,"version":"4.1.0"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/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":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pain Ther"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1007\/s40122-026-00861-8","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:17:22Z","timestamp":1787746642000},"page":"1653-1672","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Safety of Oral Zavegepant in Migraine Prevention: A Phase 2\/3 Randomized, Double-Blind, Placebo-Controlled Study in Patients with Chronic Migraine"],"prefix":"10.1007","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct04804033","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4105-1248","authenticated-orcid":false,"given":"Robert J.","family":"Fountaine","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Dubrovin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Mosher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed H.","family":"Shahin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terence","family":"Fullerton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"861_CR1","doi-asserted-by":"crossref","unstructured":"Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38:1\u2013211.","DOI":"10.1177\/0333102417738202"},{"key":"861_CR2","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1177\/0333102410381145","volume":"31","author":"AM Blumenfeld","year":"2011","unstructured":"Blumenfeld AM, Varon SF, Wilcox TK, et al. Disability, HRQoL and resource use among chronic and episodic migraineurs: results from the International Burden of Migraine Study (IBMS). Cephalalgia. 2011;31:301\u201315.","journal-title":"Cephalalgia"},{"key":"861_CR3","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1111\/head.12878","volume":"56","author":"RB Lipton","year":"2016","unstructured":"Lipton RB, Manack Adams A, Buse DC, Fanning KM, Reed ML. A comparison of the Chronic Migraine Epidemiology and Outcomes (CaMEO) study and American Migraine Prevalence and Prevention (AMPP) study: demographics and headache-related disability. Headache. 2016;56:1280\u20139.","journal-title":"Headache"},{"key":"861_CR4","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1111\/head.12755","volume":"56","author":"A Messali","year":"2016","unstructured":"Messali A, Sanderson JC, Blumenfeld AM, et al. Direct and indirect costs of chronic and episodic migraine in the United States: a web-based survey. Headache. 2016;56:306\u201322.","journal-title":"Headache"},{"key":"861_CR5","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1111\/head.14153","volume":"61","author":"J Ailani","year":"2021","unstructured":"Ailani J, Burch RC, Robbins MS, Board of Directors of the American Headache Society. The American Headache Society Consensus Statement: update on integrating new migraine treatments into clinical practice. Headache. 2021;61:1021\u201339.","journal-title":"Headache"},{"key":"861_CR6","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/S0140-6736(20)32544-7","volume":"397","author":"R Croop","year":"2021","unstructured":"Croop R, Lipton RB, Kudrow D, et al. Oral rimegepant for preventive treatment of migraine: a phase 2\/3, randomised, double-blind, placebo-controlled trial. Lancet. 2021;397:51\u201360.","journal-title":"Lancet"},{"key":"861_CR7","doi-asserted-by":"publisher","first-page":"1656","DOI":"10.3390\/jcm11061656","volume":"11","author":"D Moreno-Ajona","year":"2022","unstructured":"Moreno-Ajona D, Villar-Martinez MD, Goadsby PJ. New generation gepants: migraine acute and preventive medications. J Clin Med. 2022;11:1656.","journal-title":"J Clin Med"},{"key":"861_CR8","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1007\/s40265-023-01885-6","volume":"83","author":"S Dhillon","year":"2023","unstructured":"Dhillon S. Zavegepant: first approval. Drugs. 2023;83:825\u201331.","journal-title":"Drugs"},{"key":"861_CR9","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1111\/head.14389","volume":"62","author":"R Croop","year":"2022","unstructured":"Croop R, Madonia J, Stock DA, et al. Zavegepant nasal spray for the acute treatment of migraine: a phase 2\/3 double-blind, randomized, placebo-controlled, dose-ranging trial. Headache. 2022;62:1153\u201363.","journal-title":"Headache"},{"key":"861_CR10","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/S1474-4422(22)00517-8","volume":"22","author":"RB Lipton","year":"2023","unstructured":"Lipton RB, Croop R, Stock DA, et al. Safety, tolerability, and efficacy of zavegepant 10 mg nasal spray for the acute treatment of migraine in the USA: a phase 3, double-blind, randomised, placebo-controlled multicentre trial. Lancet Neurol. 2023;22:209\u201317.","journal-title":"Lancet Neurol"},{"key":"861_CR11","doi-asserted-by":"publisher","first-page":"333102424125945","DOI":"10.1177\/03331024241259456","volume":"44","author":"K Mullin","year":"2024","unstructured":"Mullin K, Croop R, Mosher L, Fullerton T, Madonia J, Lipton RB. Long-term safety of zavegepant nasal spray for the acute treatment of migraine: a phase 2\/3 open-label study. Cephalalgia. 2024;44:3331024241259456.","journal-title":"Cephalalgia"},{"key":"861_CR12","doi-asserted-by":"publisher","DOI":"10.1111\/cts.70048","volume":"17","author":"R Bhardwaj","year":"2024","unstructured":"Bhardwaj R, Malatesta JA, Madonia J, et al. Deconvoluting zavegepant drug-drug interactions: A phase I study to evaluate the effects of rifampin and itraconazole on zavegepant pharmacokinetics. Clin Transl Sci. 2024;17:e70048.","journal-title":"Clin Transl Sci"},{"key":"861_CR13","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1111\/head.15042","volume":"65","author":"R Bertz","year":"2025","unstructured":"Bertz R, Donohue M, Madonia J, et al. Safety, tolerability, and pharmacokinetics of single and multiple ascending doses of zavegepant nasal spray in healthy adults from two phase 1 randomized, placebo-controlled trials. Headache. 2025;65:1331\u201343.","journal-title":"Headache"},{"key":"861_CR14","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-020-1085-x","volume":"21","author":"Y Yang","year":"2020","unstructured":"Yang Y, Wang Z, Gao B, et al. Different doses of galcanezumab versus placebo in patients with migraine and cluster headache: a meta-analysis of randomized controlled trials. J Headache Pain. 2020;21:14.","journal-title":"J Headache Pain"},{"key":"861_CR15","doi-asserted-by":"publisher","first-page":"1468961","DOI":"10.3389\/fneur.2024.1468961","volume":"15","author":"A Raja","year":"2024","unstructured":"Raja A, Asim R, Shuja MH, et al. Atogepant for migraine prevention: a meta-analysis of safety and efficacy in adults. Front Neurol. 2024;15:1468961.","journal-title":"Front Neurol"},{"key":"861_CR16","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-023-01587-0","volume":"24","author":"SJ Tepper","year":"1990","unstructured":"Tepper SJ, Cirillo J, Kim E, et al. The temporal trend of placebo response in migraine prevention from 1990 to 2021: a systematic literature review and meta-analysis with regression. J Headache Pain. 1990;24:54.","journal-title":"J Headache Pain"},{"key":"861_CR17","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1177\/0333102420960020","volume":"41","author":"K Evans","year":"2021","unstructured":"Evans K, Romero H, Spierings EL, Katz N. The relation between the placebo response, observed treatment effect, and failure to meet primary endpoint: a systematic review of clinical trials of preventative pharmacological migraine treatments. Cephalalgia. 2021;41:247\u201355.","journal-title":"Cephalalgia"},{"key":"861_CR18","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1089\/cap.2019.0022","volume":"29","author":"Y Li","year":"2019","unstructured":"Li Y, Huang J, He Y, et al. The impact of placebo response rates on clinical trial outcome: a systematic review and meta-analysis of antidepressants in children and adolescents with major depressive disorder. J Child Adolesc Psychopharmacol. 2019;29:712\u201320.","journal-title":"J Child Adolesc Psychopharmacol"}],"container-title":["Pain and Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40122-026-00861-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40122-026-00861-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40122-026-00861-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:29:35Z","timestamp":1790677775000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40122-026-00861-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,26]]},"references-count":18,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["861"],"URL":"https:\/\/doi.org\/10.1007\/s40122-026-00861-8","relation":{},"ISSN":["2193-8237","2193-651X"],"issn-type":[{"value":"2193-8237","type":"print"},{"value":"2193-651X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,26]]},"assertion":[{"value":"19 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Robert J. Fountaine, Sergey Dubrovin, Linda Mosher, Jing Liu, Mohamed H. Shahin and Terence Fullerton are employed by and own stock\/stock options in Pfizer Inc.","order":1,"name":"Ethics","label":"Conflict of Interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was conducted in accordance with Good Clinical Practice guidelines, the Declaration of Helsinki and all applicable local regulations. The protocol was approved by an Institutional Review Board\/Independent Ethics Committee prior to initiation. All participants provided written informed consent prior to participating in the study. With the exception of 1 site that used a local IRB, the remaining sites utilized Advarra, the central IRB. The site that utilized the local IRB did not randomize any subjects into the trial.","order":2,"name":"Ethics","label":"Ethical Approval","group":{"name":"EthicsHeading","label":"Declarations"}}]}}