{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T23:50:47Z","timestamp":1785455447701,"version":"3.56.0"},"reference-count":24,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Centanafadine is a norepinephrine\/dopamine\/serotonin reuptake inhibitor in development for treatment of attention\u2010deficit\/hyperactivity disorder. This double\u2010blind, placebo\u2010 and moxifloxacin\u2010controlled, 3\u2010period crossover trial evaluated the effects of centanafadine (EB\u20101020) and its metabolite (EB\u201010601) on cardiac repolarization in 30 healthy adults (18\u201065\u00a0years). Dosing sequences included centanafadine sustained\u2010release 800\u00a0mg (supratherapeutic) total daily dose, placebo, and moxifloxacin 400\u00a0mg. Electrocardiogram parameters and heart rate (HR) were assessed. The primary endpoint was placebo\u2010corrected change from baseline QTc (\u0394\u0394QTc), analyzed using concentration\u2010QTc (C\u2010QTc) analysis. The C\u2010QTc slopes for centanafadine (\u22120.001\u00a0ms\/[ng\/mL]) and EB\u201010601 (\u22120.0003\u00a0ms\/[ng\/mL]) were not statistically significant. Assay sensitivity was confirmed by the statistically significant C\u2010QTc slope for moxifloxacin (0.004\u00a0ms\/[ng\/mL]) and a 2\u2010sided 90% confidence interval lower bound &gt;5\u00a0milliseconds. No change from baseline in QTcF or placebo\u2010corrected QTcF \u226510\u00a0milliseconds for centanafadine was observed at any postdose time point. No centanafadine\u2010treated participants had QTcF increases of &gt;30\u00a0milliseconds and no relevant PR\/QRS interval or HR increases were observed. The predicted \u0394\u0394QTcF values of centanafadine, EB\u201010601, and moxifloxacin at the geometric mean C<jats:sub>max<\/jats:sub> were \u22122.72, \u22121.59, and 11.75\u00a0milliseconds, respectively. No serious treatment\u2010emergent adverse events or deaths were reported. Centanafadine was generally safe and well\u2010tolerated, with no clinically meaningful effect on cardiac repolarization.<\/jats:p>","DOI":"10.1002\/cpdd.1545","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T13:44:22Z","timestamp":1748353462000},"page":"621-630","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Randomized Thorough QT Trial Using Concentration\u2010QT Analysis to Evaluate the Effects of Centanafadine on Cardiac Repolarization"],"prefix":"10.1002","volume":"14","author":[{"given":"Osman S.","family":"Turkoglu","sequence":"first","affiliation":[{"name":"Otsuka Pharmaceutical Development &amp; Commercialization, Inc.  Rockville MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development &amp; Commercialization, Inc.  Rockville MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Repella\u2010Gordon","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development &amp; Commercialization, Inc.  Rockville MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan E.","family":"Shoaf","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development &amp; Commercialization, Inc.  Rockville MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,27]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"Diagnostic and Statistical Manual of Mental Disorders","year":"2013"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2015.14101266"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12888-017-1463-3"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.7189\/jogh.11.04009"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.18553\/jmcp.2021.21290"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/15374416.2024.2335625"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0000000000001575"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S242084"},{"issue":"1","key":"e_1_2_10_10_1","first-page":"8","article-title":"Mass balance and pharmacokinetics of a single oral dose of 14C\u2010centanafadine in healthy adult subjects","volume":"8","author":"Mehrotra S","year":"2019","journal-title":"Clin Pharmacol Drug Develop"},{"issue":"1","key":"e_1_2_10_11_1","first-page":"63","article-title":"Effect of moderate hepatic or severe renal impairment on pharmacokinetics of centanafadine","volume":"10","author":"Mehrotra S","year":"2021","journal-title":"Clin Pharmacol Drug Develop"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.21538"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/02698811221140008"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270006286436"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.33"},{"issue":"1","key":"e_1_2_10_16_1","first-page":"1","article-title":"The construction of a williams design and randomization in cross\u2010over clinical trials using SAS","volume":"29","author":"Wang B\u2010S","year":"2009","journal-title":"J Stat Soft"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.60"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/anec.12227"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.2147\/DHPS.S133286"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2012.04382.x"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.20m13395"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-012-0019-9"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.528"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/1060028013501994"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/jce.13235"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1545","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T03:50:56Z","timestamp":1754020256000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.1545"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,27]]},"references-count":24,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/cpdd.1545"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.1545","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,27]]},"assertion":[{"value":"2025-01-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}