{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T17:26:46Z","timestamp":1786987606876,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>Milvexian, an activated factor XI inhibitor, is being evaluated in the LIBREXIA phase III program for the prevention of thrombotic events, including in patients with atrial fibrillation (LIBREXIA AF). To guide the selection of a phase III dose regimen for LIBREXIA AF, two main approaches were used: (1) population pharmacokinetics and exposure\u2013response modeling of milvexian phase I and phase II (AXIOMATIC\u2010TKR) study data was performed to characterize the relationship between milvexian population pharmacokinetics and clinical efficacy, safety, and coagulation biomarkers;\u00a0and (2) a model\u2010based meta\u2010analysis was developed using published clinical trial data from comparator anticoagulants in total hip or knee replacement patients. When used to simulate exposures for an atrial fibrillation population, the milvexian 100\u2009mg twice\u2010daily dose regimen had a concentration maximum peak\u2010to\u2010trough ratio of 1.35. At this regimen, the simulated median venous thromboembolism rate was 9.4% (lower than enoxaparin at ~21%). No relationship between bleeding and milvexian exposure was observed. Simulations using the model\u2010based meta\u2010analysis estimated that milvexian 100\u2009mg twice\u2010daily would lead to a systemic embolism odds ratio of 0.84 (95% CI: 0.65, 1.12) compared with apixaban 5\u2009mg twice\u2010daily for patients with atrial fibrillation. This integrated model\u2010informed dose\u2010selection approach supported 100\u2009mg twice\u2010daily as a regimen of milvexian to be evaluated in the phase III milvexian LIBREXIA AF study.<\/jats:p>","DOI":"10.1002\/cpt.70037","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T13:45:01Z","timestamp":1755870301000},"page":"139-146","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Quantitative Model\u2010Informed Dose Selection for a Milvexian Phase III Study in Patients With Atrial Fibrillation"],"prefix":"10.1002","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5902-0709","authenticated-orcid":false,"given":"Wangda","family":"Zhou","sequence":"first","affiliation":[{"name":"Johnson &amp; Johnson  Raritan New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Bozenhardt","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Raritan New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory E.","family":"Alexander","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5221-9157","authenticated-orcid":false,"given":"Matthew L.","family":"Zierhut","sequence":"additional","affiliation":[{"name":"Certara USA Inc.  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