Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Milvexian in Healthy Chinese Adults.

BACKGROUND

Milvexian is a small molecule, selective factor XIa (FXIa) inhibitor being developed as an oral anticoagulant. This study assessed the pharmacokinetics, pharmacodynamics (activated partial thromboplastin time [aPTT]), and safety of milvexian in healthy Chinese subjects.

METHODS

Part 1: Thirty subjects were randomly assigned 1:1:1 to receive milvexian 25 mg on Day 1 followed by 25 mg once daily (QD) on Days 5-12; milvexian 25 mg twice daily at 12-hour intervals (BID) on Days 1-8; or milvexian 100 mg BID on Days 1-8. Part 2: Ten subjects received milvexian 200 mg on Day 1 followed by 200 mg BID on Days 5-12. Plasma samples were collected for pharmacokinetics and aPTT assessments. Safety and tolerability were assessed.

RESULTS

Milvexian was rapidly absorbed (median tmax of 3-4 hours after a single dose and repeated administration). Mean maximum concentrations or area under the concentration-time curve values of milvexian in plasma after single doses or BID administration of 25 mg, 100 mg, or 200 mg increased in a dose-dependent manner. Steady state conditions were achieved within 6 days of repeated administration based on milvexian trough concentration values. Mean terminal half-life values (9-10 hours) were independent of the dose. Milvexian reversibly prolonged aPTT in a manner that was directly related to milvexian dose and exposure. All milvexian regimens were safe and well tolerated, with only mild treatment-emergent adverse events and no clinically significant bleeding events. No new safety signals were identified.

CONCLUSION

The pharmacokinetic, pharmacodynamic, and safety profiles of milvexian demonstrate suitability for further clinical development in Chinese participants.