{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T14:42:11Z","timestamp":1793889731877,"version":"4.8.0"},"reference-count":8,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,11,6]],"date-time":"2021-11-06T00:00:00Z","timestamp":1636156800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,11,6]],"date-time":"2021-11-06T00:00:00Z","timestamp":1636156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","award":["Study sponsored by Eli Lilly and Company"],"award-info":[{"award-number":["Study sponsored by Eli Lilly and Company"]}],"id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Headache Pain"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Lasmiditan (LTN) is a selective 5-HT<jats:sub>1F<\/jats:sub> receptor agonist for the acute treatment of migraine in adults. We present detailed safety findings from the placebo-controlled, double-blind Phase 3 study, of LTN treatment across 4 attacks (CENTURION).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Patients were randomized 1:1:1 to LTN 200\u00a0mg (LTN200), LTN100, or a control group that received placebo for 3 attacks and LTN50 for either the 3rd or 4th attack (1:1). Safety analyses were conducted for patients who took \u22651 dose of study drug and, in some cases, those who took all 4 doses.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Overall, 1471 patients treated 4494 attacks. The incidences of treatment-emergent serious adverse events (SAEs) were - placebo, <jats:italic>n<\/jats:italic>=2 (0.4\u2009%); LTN100, <jats:italic>n<\/jats:italic>=1 (0.2\u2009%); LTN200, <jats:italic>n<\/jats:italic>=2 (0.4\u2009%); no specific treatment-emergent SAE was reported in more than one patient. The most common treatment emergent adverse events (TEAEs) with lasmiditan were dizziness, paresthesia, fatigue, nausea, vertigo, and somnolence; the vast majority were mild or moderate in severity. The incidences of these TEAEs were highest during the first attack and decreased during subsequent attacks. For patients who experienced a common TEAE with the first attack, less than 45\u2009% experienced the same event in subsequent attacks. Patients who did not experience an event in the 1st attack infrequently experienced the same event in subsequent attacks.<\/jats:p>\n                <jats:p>The time of onset of the common TEAE ranged from ~40\u00a0min to 1\u00a0h (dependent upon TEAE) and, for individual TEAE, the onset was similar across attacks. Duration was dependent upon TEAE and attack. It was shortest for paresthesia (&lt; 2\u00a0h for all attacks); it ranged from 1.8 to 5.5\u00a0h for other common TEAEs and was generally similar across attacks.<\/jats:p>\n                <jats:p>Serotonin syndrome was reported for 2 patients post LTN dosing; there were no meaningful differences across treatment groups in suicidality; there was no evidence of an increase in motor vehicle accidents.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>In this blinded, controlled, multiple-attack study, LTN was associated with generally mild or moderate CNS-related TEAEs of short duration. TEAEs tended to decrease in frequency across the 4 attacks.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03670810\">NCT03670810<\/jats:ext-link><\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s10194-021-01343-2","type":"journal-article","created":{"date-parts":[[2021,11,6]],"date-time":"2021-11-06T19:02:49Z","timestamp":1636225369000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Safety findings from CENTURION, a phase 3 consistency study of lasmiditan for the acute treatment of migraine"],"prefix":"10.1186","volume":"22","author":[{"given":"C","family":"Tassorelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Bragg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JH","family":"Krege","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"EG","family":"Doty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"PA","family":"Ardayfio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Ruff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SA","family":"Dowsett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Schwedt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,6]]},"reference":[{"key":"1343_CR1","unstructured":"(2019) REYVOW\u00ae (lasmiditan) tablets [package insert]. Eli Lilly and Company, Indianapolis.\u00a0http:\/\/pi.lilly.com\/us\/reyvow-uspi.pdf. Accessed 31\u00a0Oct\u00a02020"},{"key":"1343_CR2","doi-asserted-by":"publisher","first-page":"e2222","DOI":"10.1212\/WNL.0000000000006641","volume":"91","author":"B Kuca","year":"2018","unstructured":"Kuca B, Silberstein SD, Wietecha L et al (2018) Lasmiditan is an effective acute treatment for migraine: a phase 3 randomized study. Neurology 91:e2222\u2013e2232","journal-title":"Neurology"},{"key":"1343_CR3","doi-asserted-by":"crossref","unstructured":"Goadsby PJ, Wietecha LA, Dennehy EB et al (2019) Phase 3 randomized, placebo-controlled, double-blind study of lasmiditan for acute treatment of migraine. Brain 142:1894\u20131904","DOI":"10.1093\/brain\/awz134"},{"key":"1343_CR4","doi-asserted-by":"publisher","unstructured":"Ashina M, Reuter U, Smith T et al (2021) Randomized, controlled trial of lasmiditan over four migraine attacks: findings from the CENTURION study. Cephalalgia. https:\/\/doi.org\/10.1177\/0333102421989232.","DOI":"10.1177\/0333102421989232"},{"key":"1343_CR5","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1177\/0333102419855080","volume":"39","author":"JH Krege","year":"2019","unstructured":"Krege JH, Rizzoli PB, Liffick E et al (2019) Safety findings from phase 3 lasmiditan studies for acute treatment of migraine: results from SAMURAI and SPARTAN. Cephalalgia 39:957\u2013966","journal-title":"Cephalalgia"},{"key":"1343_CR6","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1176\/appi.ajp.2011.10111704","volume":"168","author":"K Posner","year":"2011","unstructured":"Posner K, Brown GK, Stanley B et al (2011) The Columbia\u2013suicide severity rating scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry 168:1266\u20131277","journal-title":"Am J Psychiatry"},{"key":"1343_CR7","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1111\/head.13731","volume":"60","author":"D Kudrow","year":"2020","unstructured":"Kudrow D, Krege JH, Hundemer HP et al (2020) Issues impacting adverse event frequency and severity: differences between randomized phase 2 and phase 3 clinical trials for lasmiditan. Headache 60:576\u2013588","journal-title":"Headache"},{"key":"1343_CR8","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1177\/0333102419864132","volume":"39","author":"JL Brandes","year":"2019","unstructured":"Brandes JL, Klise S, Krege JH et al (2019) Interim results of a prospective, randomized, open-label, phase 3 study of the long-term safety and efficacy of lasmiditan for acute treatment of migraine (the GLADIATOR study). Cephalalgia 39:1343\u20131357","journal-title":"Cephalalgia"}],"container-title":["The Journal of Headache and Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10194-021-01343-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s10194-021-01343-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10194-021-01343-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,6]],"date-time":"2021-11-06T19:03:13Z","timestamp":1636225393000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejournalofheadacheandpain.biomedcentral.com\/articles\/10.1186\/s10194-021-01343-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,6]]},"references-count":8,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1343"],"URL":"https:\/\/doi.org\/10.1186\/s10194-021-01343-2","relation":{},"ISSN":["1129-2369","1129-2377"],"issn-type":[{"value":"1129-2369","type":"print"},{"value":"1129-2377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,6]]},"assertion":[{"value":"17 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 October 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 November 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study received approval from the relevant Ethics Committees and participants provided written informed consent for study participation. The study was conducted in accordance with the Declaration of Helsinki. A list of ethics review committees are provided in the supplement.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"CT has received fees for advisory boards or scientific lecturing from Allergan\/Abbvie, Eli Lilly and Company, Novartis, and TEVA; and institutional payments for clinical trials from Allergan\/Abbvie, Eli Lilly and Company, Novartis, and TEVA. SB, JHK, EGD, PAA, DR, SAD are full time employees and minor stockholders at Eli Lilly and Company. Within the prior 24 months, TS has consulted with Alder, Allergan, Amgen, Biohaven, Click Therapeutics, Eli Lilly and Company, Equinox, Ipsen, Lundbeck, Novartis, Tonix, Weber and Weber, and XoC; received research grants from Amgen; and has stock options with Aural Analytics and Nocira.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"132"}}