{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T17:26:21Z","timestamp":1786987581111,"version":"build-2736575974"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Milvexian is an oral factor XIa inhibitor in development for prevention of major thromboembolic conditions. This randomized, double\u2010blind, placebo\u2010 and positive\u2010controlled, multiple\u2010dose, four\u2010period crossover study assessed the cardic safety of milvexian (including effects on the QT interval of the electrocardiogram), with a supporting in vitro component. Sixty\u2010six participants were enrolled. In each treatment period, participants received milvexian (100 or 200\u00a0mg) or placebo every 12\u00a0h for 4\u00a0days. A single\u2010dose moxifloxacin (400\u00a0mg) served as a positive control. Electrocardiographs and time\u2010matched pharmacokinetic samples were collected during each period. In mixed\u2010effects models, the upper limit of the two\u2010sided 90% confidence interval for the least squares means for change from baseline QTc (Fridericia [QTcF], as the primary correction method) for milvexian versus placebo (\u0394\u0394QTc) was \u02c210 ms at all time points after each milvexian regimen. In addition, there was no apparent relationship between \u0394\u0394QTcF and plasma milvexian concentrations. Moxifloxacin response confirmed assay sensitivity. Milvexian inhibited human ether\u2010a\u2010go\u2010go\u2010related gene potassium, sodium, and L\u2010type calcium ion channel currents with weak\u2010to\u2010moderate potency at concentrations exceeding the highest mean unbound maximum plasma concentrations of TQT study participants. Milvexian regimens were safe and well tolerated. These data indicate that milvexian does not prolong the QTc interval at clinically relevant concentrations.<\/jats:p>","DOI":"10.1002\/cpdd.70015","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T08:53:01Z","timestamp":1768812781000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Thorough QT Study to Assess the Effects of Milvexian on Cardiac Repolarization in Healthy Participants"],"prefix":"10.1002","volume":"15","author":[{"given":"Peter","family":"Zannikos","sequence":"first","affiliation":[{"name":"Johnson &amp; Johnson  Raritan NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JongHanne","family":"Park","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Raritan NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Dari","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samiha","family":"Takhtoukh","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Levesque","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Princeton NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexei N.","family":"Plotnikov","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Raritan NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amitava","family":"Mitra","sequence":"additional","affiliation":[{"name":"Kura Oncology, Inc.  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoinette","family":"Ajavon\u2010Hartmann","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Princeton NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samira","family":"Merali","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Princeton NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Jose","family":"Perez Ruixo","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navin","family":"Goyal","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Raritan NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-022-00787-6"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.124.320151"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.306841"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2017.5306"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-146-4-200702200-00007"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH16-11-0876"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2007.02847.x"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2019.02.060"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2016.05.041"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3310\/hta21090"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1055\/a-2061-3311"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.15588"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c00613"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13148"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.70058"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40119-022-00266-6"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-022-01110-9"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-022-01150-1"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2113194"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00403-9"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1461-5347(99)00172-8"},{"key":"e_1_2_11_23_1","unstructured":"European Medicines Agency; 2005 ICH Topic E14 The clinical evaluation of QT\/QTc interval prolongation and proarrhythmic potential for non\u2010antiarrhythmic drugs"},{"key":"e_1_2_11_24_1","unstructured":"E14 clinical evaluation of QT\/QTc interval prolongation and proarrhythmic potential for non\u2010antiarrhythmic drugs\u2014questions and answers (R3).Guidance for Industry. 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