PII-070 - PHARMACOKINETIC/PHARMACODYNAMIC ANALYSIS OF APIXABAN TO DETERMINE DOSING REGIMENS FOR PEDIATRIC PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA OR LYMPHOBLASTIC LYMPHOMA TREATED WITH ASPARAGINASE: ANALYSIS FROM THE PREVAPIX STUDY.

P. Jarugula¹, T. Ajavon-Hartmann¹, O. Obianom², E. Ludwig², C. Crevar¹, D. Marchisin¹, Z. Wang¹, W. Chen¹, B. He¹, V. Perera¹, B. Murthy¹, S. Merali¹; ¹Bristol Myers Squibb, Lawrenceville, NJ, USA, ²Simulations Plus Inc., Buffalo, NY, USA.

Background: Apixaban may be a treatment option for thromboembolism prevention in children with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL). This analysis characterized apixaban pharmacokinetics (PK) and PK/pharmacodynamics (PD) in pediatric patients (pts) with ALL/LL to recommend doses in pts aged 28 days to < 18 years.

Methods: Data from a Phase 3 pediatric study (NCT02369653, N = 224) were used to update a previously developed population PK model and assess the covariate effect of pt type on PK parameters, while retaining previous covariates. Stochastic simulations were performed to identify doses in pediatric pts that matched adult exposures (2.5 mg bid). The relationship between anti-factor Xa (AXA) and apixaban concentration was also evaluated.

Results: Apixaban apparent volume of distribution and absorption rate constant were lower (~26% and ~80%, respectively) in pediatric pts with ALL/LL compared to adults. Simulations of proposed fixed doses by weight tiers demonstrated apixaban steady state exposures in pediatric pts were consistent with adult exposures (Figure). The apixaban PK–AXA relationship was characterized well using linear regression.

Conclusion: Apixaban PK and PK/PD were well characterized. Steady state exposures in pediatric pts were consistent with adult exposures.

Comparison of Exposure Between Pediatric Patients Aged (A) 1 to < 18 years and (B) 28 Days to < 18 Years by Weight Tiers and Adult VTE Prevention Population From AMPLIFY EXT Study