Journal Article

Safety, tolerability, pharmacokinetics and pharmacodynamics of milvexian with aspirin and/or clopidogrel in healthy participants

Wang, Zhaoqing, Perera, Vidya, Lubin, Susan, Abelian, Grigor, Li, Danshi, Luettgen, Joseph, Aronson, Ronald, Zhang, Liping, Murthy, Bindu, Merali, Samira

2024

Overview

Milvexian, an oral activated Factor XI (FXIa) inhibitor, is in clinical studies where it may be combined with antiplatelet agents, including aspirin and/or clopidogrel, to prevent thromboembolic diseases. This phase I trial assessed safety, pharmacokinetics, and pharmacodynamics of milvexian coadministration with aspirin and/or clopidogrel in healthy participants through 3 drug-drug interaction studies using a 3-period, 3-treatment, crossover design. A total of 113 participants were randomized to receive milvexian (200 mg; twice daily for 5 days) or matched placebo coadministered with once-daily aspirin (325 mg for 5 days) and/or clopidogrel (Day 1: 300 mg; Days 2–5: 75 mg). Milvexian was safe and well tolerated, with and without aspirin and/or clopidogrel. Eight mild bleeding adverse events (AEs) were reported in 5 of 113 participants across various treatment arms. Peak and total exposures of milvexian were similar with or without clopidogrel and/or aspirin. Exposure-dependent prolongation of activated partial thromboplastin time and reduction of FXI clotting activity by milvexian were similar with coadministration of aspirin and/or clopidogrel. Milvexian, with or without coadministration of aspirin and/or clopidogrel, did not affect bleeding time or platelet aggregation. Administration of milvexian alone or with aspirin and/or clopidogrel was safe and well tolerated without increased incidence of AEs, including bleeding. Pharmacokinetic and pharmacodynamic effects of milvexian, including bleeding time, were similar with or without aspirin and/or clopidogrel. ClinicalTrials.gov Identifier : NCT03698513.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/154/436 / 692/699/75/593/567 / Adult / Antiplatelet therapy / Aspirin / Aspirin - administration & dosage / Aspirin - pharmacokinetics / Bleeding / Clopidogrel / Clopidogrel - administration & dosage / Clopidogrel - adverse effects / Clopidogrel - pharmacokinetics / Clotting / Coagulation factors / Cross-Over Studies / Drug development / Drug interaction / Drug Interactions / Female / Healthy Volunteers / Humanities and Social Sciences / Humans / Male / Middle Aged / multidisciplinary / Pharmacodynamics / Pharmacokinetics / Platelet aggregation / Platelet Aggregation Inhibitors - administration & dosage / Platelet Aggregation Inhibitors - adverse effects / Platelet Aggregation Inhibitors - pharmacokinetics / Platelet Aggregation Inhibitors - pharmacology / Science / Science (multidisciplinary) / Thromboembolism / Thromboplastin / Young Adult