{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T20:12:51Z","timestamp":1777407171527,"version":"3.51.4"},"reference-count":8,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T00:00:00Z","timestamp":1666742400000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100014091","name":"AstraZeneca Pharma Poland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014091","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2022,10]]},"abstract":"Abstract<\/jats:title>\n \n Objective<\/jats:title>\n To evaluate the efficacy and safety of zolmitriptan nasal spray (ZNS) in the acute treatment of migraine headache in patients aged 6 to 11\u2009years.<\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n Triptans have demonstrated efficacy in adults, but pediatric studies of these agents have largely failed and there are few triptan options for these patients. Because lack of response to 1 triptan does not necessarily preclude response to an alternate triptan, additional triptan options for pediatric patients are desirable.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This Phase 3, randomized, double\u2010blind, placebo\u2010controlled, multicenter crossover trial with an open\u2010label extension enrolled patients aged 6 to 11\u2009years with a diagnosis of migraine for \u22656\u00a0months and \u226516 headache\u2010free days\/month (\n N<\/jats:italic>\n \u00a0=\u00a0373). After a run\u2010in period to eliminate placebo responders, 186 patients were randomized within their body weight stratum to ZNS followed by matching placebo, or placebo followed by matching ZNS. Patients <50\u2009kg who were randomly allocated to ZNS were randomized to 5:1 to ZNS 2.5 or 1.0\u00a0mg; those \u226550\u2009kg were randomized 5:1 to ZNS 5.0 or 2.5\u00a0mg. Patients had 6\u2009weeks to treat 1 moderate to severe migraine headache and then crossed over to the alternate arm, during which they had 6\u2009weeks to treat a second migraine attack. Patients could participate in a subsequent 6\u2010month outpatient open\u2010label extension. The primary efficacy endpoint was pain\u2010free status at 2\u00a0h in patients treated with the high dose from each stratum.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The trial was terminated early due to slow enrollment. Three hundred patients (mean age, 9\u2009years) entered the placebo run\u2010in period and 186 entered the double\u2010blind period. Pain\u2010free status at 2\u00a0h postdose was achieved by 45\/133 (33.8%) and 30\/128 (23.4%) of patients who received high\u2010dose ZNS and placebo, respectively (\n p<\/jats:italic>\n \u00a0=\u00a00.0777; odds ratio [OR] 1.51; 95% confidence interval [CI] 0.96, 2.38). Several secondary endpoints achieved statistical significance. There were few treatment\u2010related adverse events and none led to discontinuation. ZNS retained efficacy and demonstrated a consistent safety profile throughout the 6\u2010month open\u2010label extension.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n The effect of high\u2010dose ZNS on the primary endpoint of pain\u2010free status at 2\u00a0h did not achieve statistical significance. ZNS was safe and well tolerated in this pediatric population.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/head.14391","type":"journal-article","created":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T09:14:46Z","timestamp":1666775686000},"page":"1207-1217","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A multicenter, randomized, double\u2010blind, placebo\u2010controlled, crossover trial to evaluate the efficacy and safety of zolmitriptan nasal spray for the acute treatment of migraine in patients aged 6 to 11\u2009years, with an open\u2010label extension"],"prefix":"10.1111","volume":"62","author":[{"given":"Marcy E.","family":"Yonker","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Colorado School of Medicine, Children's Hospital Colorado Aurora Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0018-1644","authenticated-orcid":false,"given":"Jennifer","family":"McVige","sequence":"additional","affiliation":[{"name":"Pediatric Neurology and Concussion Center Dent Neurologic Institute Amherst New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonid","family":"Zeitlin","sequence":"additional","affiliation":[{"name":"Quartesian LLC Princeton New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hester","family":"Visser","sequence":"additional","affiliation":[{"name":"Amneal Pharmaceuticals LLC Bridgewater New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,10,26]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000008095"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1526-4610.2002.02013.x"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2004.04171.x"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2013.872"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-2982.2008.01752.x"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-013-0342-y"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-2982.2003.00554.x"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102412451358"}],"container-title":["Headache: The Journal of Head and Face Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/head.14391","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/head.14391","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/headachejournal.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/head.14391","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T10:32:09Z","timestamp":1767609129000},"score":1,"resource":{"primary":{"URL":"https:\/\/headachejournal.onlinelibrary.wiley.com\/doi\/10.1111\/head.14391"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10]]},"references-count":8,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1111\/head.14391"],"URL":"https:\/\/doi.org\/10.1111\/head.14391","archive":["Portico"],"relation":{},"ISSN":["0017-8748","1526-4610"],"issn-type":[{"value":"0017-8748","type":"print"},{"value":"1526-4610","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10]]},"assertion":[{"value":"2022-02-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}