Quantitative Model-Informed Dose Selection for a Milvexian Phase III Study in Patients With Atrial Fibrillation

Milvexian is an investigational anticoagulant being developed to prevent harmful blood clots with potentially reduced bleeding risk compared to current therapies. To identify the most appropriate dose for a phase III clinical trial in atrial fibrillation, researchers applied multiple quantitative approaches. Population pharmacokinetic and exposure–response models were developed using phase I and phase II clinical data to evaluate how milvexian levels in the body relate to clot prevention, bleeding risk, and biomarker changes.

In parallel, a model-based meta-analysis compared milvexian’s expected performance with approved anticoagulants using published trial data. Together, these analyses supported selecting a 100 mg twice-daily dose for further evaluation, balancing efficacy with a favorable bleeding profile.

This study demonstrates how model-informed approaches can improve dose selection decisions when direct clinical comparisons or validated biomarkers are limited.