{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T06:57:28Z","timestamp":1783407448408,"version":"3.54.6"},"reference-count":24,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T00:00:00Z","timestamp":1716940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Zavegepant is a novel gepant administered as a nasal spray approved in the United States at a 10\u2009mg dose for the acute treatment of migraine with or without aura in adults. The cardiovascular safety of zavegepant nasal spray was assessed in both single\u2010ascending dose (SAD) and multiple\u2010ascending dose (MAD) studies in healthy participants. The SAD study included 72 participants (54 active\/18 placebo) who received 0.1\u201340\u2009mg zavegepant or placebo. The MAD study included 72 participants (56 active\/16 placebo) who received 5\u201340\u2009mg zavegepant or placebo for 1\u201314\u2009days. Plasma zavegepant pharmacokinetics and electrocardiographic (ECG) parameters (Fridericia\u2010corrected QT interval [QTcF], heart rate, PR interval, ventricular depolarization [QRS], T\u2010wave morphology, and U\u2010wave presence) were analyzed pre\u2010 and post\u2010zavegepant administration. Using pooled data from the SAD and MAD studies, the relationship between time\u2010matched plasma zavegepant concentrations and QTc interval was assessed using a linear mixed\u2010effects model to evaluate the potential for QTc interval prolongation. Results showed that single and multiple doses of zavegepant had no significant impact on ECG parameters versus placebo, and there was no concentration\u2010dependent effect on QTcF interval. The estimated slope of the plasma zavegepant concentration\u2010QTcF model was \u22120.053\u2009ms per ng\/mL with a 90% confidence interval of \u22120.0955 to \u22120.0110 (<jats:italic>p<\/jats:italic>\u2009=\u20090.0415), which is not considered clinically meaningful. At doses up to four times the recommended daily dose, zavegepant does not prolong the QT interval to any clinically relevant extent.<\/jats:p>","DOI":"10.1002\/psp4.13140","type":"journal-article","created":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T09:59:14Z","timestamp":1717063154000},"page":"1044-1054","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<scp>Concentration\u2010QTc<\/scp> and cardiac safety analysis of single and multiple zavegepant nasal spray doses in healthy participants to support approval"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1862-5805","authenticated-orcid":false,"given":"Jim H.","family":"Hughes","sequence":"first","affiliation":[{"name":"Pfizer Research and Development Pfizer  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4593-1310","authenticated-orcid":false,"given":"Richard","family":"Bertz","sequence":"additional","affiliation":[{"name":"Biohaven Pharmaceuticals Inc  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2720-2192","authenticated-orcid":false,"given":"Rajinder","family":"Bhardwaj","sequence":"additional","affiliation":[{"name":"Certara USA  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0450-5702","authenticated-orcid":false,"given":"Mary K.","family":"Donohue","sequence":"additional","affiliation":[{"name":"Biohaven Pharmaceuticals Inc  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8060-8478","authenticated-orcid":false,"given":"Jennifer","family":"Madonia","sequence":"additional","affiliation":[{"name":"Biohaven Pharmaceuticals Inc  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3940-7056","authenticated-orcid":false,"given":"Matt S.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Certara USA  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4347-2042","authenticated-orcid":false,"given":"Beth A.","family":"Morris","sequence":"additional","affiliation":[{"name":"Biohaven Pharmaceuticals Inc  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S.","family":"Croop","sequence":"additional","affiliation":[{"name":"Biohaven Pharmaceuticals Inc  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9481-5961","authenticated-orcid":false,"given":"Jing","family":"Liu","sequence":"additional","affiliation":[{"name":"Pfizer Research and Development Pfizer  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,29]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102417738202"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.14024"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-022-01402-2"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2012.02185.x"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-022-06184-8"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-023-11706-1"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.14153"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.14245"},{"key":"e_1_2_11_10_1","unstructured":"FDA.Zavegepant prescribing information.2023. Accessed July 18 2023.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/216386s000lbl.pdf"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.14389"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(22)00517-8"},{"key":"e_1_2_11_13_1","first-page":"101","article-title":"Absorption, distribution, metabolism, and elimination of 5 mg [14C]\u2010zavegepant in healthy male subjects after a single intravenous infusion dose","volume":"62","author":"Bhardwaj R","year":"2022","journal-title":"Headache"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2013.04.012"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfac013"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.2147\/dhps.S133286"},{"key":"e_1_2_11_17_1","unstructured":"BertzR DonohueMK MadoniaJ et\u00a0al.Safety Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of Intranasal Zavegepant in Healthy Adults. 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