Apixaban for treatment of venous thromboembolism (VTEtx): Use of MBMA to support Phase 3 dose selection and beyond

Apixaban is an orally available, direct, selective inhibitor of the coagulation factor Xa that reversibly binds to the active site of FXa, and exerts anticoagulant and antithrombotic effects by diminishing the conversion of prothrombin to thrombin. Apixaban is approved in multiple regions for VTEtx, based on the results of a Phase 3 study (AMPLIFY [1]). Model-Based Meta-Analyses (MBMA) can inform drug development decisions and increase the probability of technical success. Here we describe how the results of MBMA were used to support dose selection for the Phase 3 VTEtx study of apixaban (apixaban 10 mg twice daily [BID] for 7 days, followed by 5 mg BID in AMPLIFY) and how the models were updated and used during the conduct of the study to address questions and inform decisions…