{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:18:14Z","timestamp":1791235094182,"version":"4.1.0"},"reference-count":11,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T00:00:00Z","timestamp":1722384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004326","name":"Bayer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>There is an unmet clinical need for effective anticoagulant therapies for the management of thromboembolic diseases that are not associated with a relevant risk of bleeding. Asundexian (BAY 2433334) is an oral, direct, small\u2010molecule inhibitor of activated factor XI (FXIa). Phase I data from healthy Caucasian male participants indicated predictable pharmacokinetic (PK) and pharmacodynamic (PD) profiles and no clinically relevant bleeding\u2010related adverse events (AEs). Reported here are data from two phase I, randomized, placebo\u2010controlled, single\u2010 and multiple\u2010dose escalation studies of asundexian conducted in 60 healthy men: 24 Japanese and 36 Chinese. Baseline characteristics were comparable between the treatment groups. All treatment\u2010emergent AEs were mild, with no serious AEs or AEs of special interest reported. Systemic exposure to asundexian increased dose proportionally after single or multiple dosing, with relatively low accumulation following multiple once\u2010daily dosing in both Chinese and Japanese volunteers. Asundexian induced dose\u2010dependent prolongation of activated partial thromboplastin time and inhibition of FXIa activity, with no effects on prothrombin time or FXI concentration in Japanese participants. There were no clinically relevant interethnic differences in PK profile across the Japanese, Chinese, and Caucasian (data from the previous phase I study) participants and no clinically relevant difference in PD response between Japanese and Caucasian participants.<\/jats:p>","DOI":"10.1111\/cts.13895","type":"journal-article","created":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T09:43:39Z","timestamp":1722419019000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Pharmacokinetics, pharmacodynamics, and safety of asundexian in healthy Chinese and Japanese volunteers, and comparison with Caucasian data"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0268-2976","authenticated-orcid":false,"given":"Huijun","family":"Chen","sequence":"first","affiliation":[{"name":"Research &amp; Development, Pharmaceuticals, Bayer AG  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6922-6548","authenticated-orcid":false,"given":"Kensei","family":"Hashizume","sequence":"additional","affiliation":[{"name":"Research &amp; Development Japan, Bayer Yakuhin, Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1346-9336","authenticated-orcid":false,"given":"Friederike","family":"Kanefendt","sequence":"additional","affiliation":[{"name":"Research &amp; Development, Pharmaceuticals, Bayer AG  Wuppertal\/Leverkusen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6515-8296","authenticated-orcid":false,"given":"Christine","family":"Brase","sequence":"additional","affiliation":[{"name":"Research &amp; Development, Pharmaceuticals, Bayer AG  Wuppertal\/Leverkusen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6714-2297","authenticated-orcid":false,"given":"Sebastian","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Research &amp; Development, Pharmaceuticals, Bayer AG  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3462-2163","authenticated-orcid":false,"given":"Tianxing","family":"Liu","sequence":"additional","affiliation":[{"name":"Research &amp; Development, Pharmaceuticals, Bayer AG  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,31]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06797"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.0000046238.23903.fc"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.116.306925"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-277798"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15230"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.15439"},{"key":"e_1_2_10_8_1","unstructured":"US Food and Drug Administration.Bioanalytical method validation: guidance for industry.2018. Accessed March 19 2024.https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/bioanalytical\u2010method\u2010validation\u2010guidance\u2010industry"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318-023-00838-4"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00456-1"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.122.061612"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01588-4"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.13895","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T01:26:45Z","timestamp":1724894805000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.13895"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,31]]},"references-count":11,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1111\/cts.13895"],"URL":"https:\/\/doi.org\/10.1111\/cts.13895","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,31]]},"assertion":[{"value":"2024-04-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13895"}}