Modeling and simulation to support apixaban dose recommendation for thromboembolism prevention in pediatric subjects with congenital or acquired heart disease requiring anticoagulation–saxophone study

Authors: Ajavon-Hartmann T, Jarugula P, Back H, Obianom O, Ludwig EA, Crevar C, Marchisin D, Wang Z, Chen W, He B, Perera V, Murthy B, Merali S
Conference: ASCPT
Keywords: Apixaban, congenital or acquired heart disease, SAXOPHONE Study
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Introduction
● Apixaban is an oral, direct, selective factor Xa (FXa) inhibitor1 and may be a treatment option for venous thromboembolism prevention in children (28 days to < 18 years) with congenital or acquired heart disease  (CAHD)
● Pharmacokinetics (PK) and pharmacodynamics (PD) of apixaban have been studied in healthy adults and adult patients2,3 – The oral bioavailability of apixaban is ~50% and increases proportionally with dose (2.5–10 mg) in adults4
– Apixaban has a total clearance of ~3.3 L/h, and an ~12-hour half-life4
● Apixaban has been studied using age-appropriate oral formulations using a model developed from 2 Phase 1 and 1 Phase 3 pediatric studies (NCT01195727, NCT01707394, and NCT02369653)
● Dose selection for the pediatric population was targeted to achieve similar plasma exposure as seen in adult patients receiving venous thromboembolism treatment (VTEtx) and in the ARISTOTLE trial population

By: Ajavon-Hartmann T, Jarugula P, Back H, Obianom O, Elizabeth Ludwig, Crevar C, Marchisin D, Wang Z, Chen W, He B, Perera V, Murthy B, and Merali S.

Poster presented at the American Society for Clinical Pharmacology and Therapeutics (ASCPT) Annual Meeting; March 22-24, 2023; Atlanta, GA.