EP-033 - A PHASE 1, OPEN-LABEL, SINGLE-DOSE, NON-RANDOMIZED STUDY TO EVALUATE PHARMACOKINETICS AND PHARMACODYNAMICS OF EDOXABAN IN PEDIATRIC PATIENTS.

P. Zou¹, H. Zahir², A. Duggal¹, G. Pandya¹, J. Jin¹, T. Leil¹; ¹Daiichi Sankyo Inc., Basking Ridge, NJ, United States, ²Daiichi Sankyo Inc., Plano, TX, United States.

Background: This first-in-pediatric study evaluated edoxaban for the treatment of VTE in pediatric patients, targeting exposures similar to those of the 30 mg and 60 mg QD doses for adults.

Methods: This was an open-label, single-dose, phase I study to characterize the PK, PD, and safety of a single dose of edoxaban in pediatric patients aged 0.008–18 years. Children requiring anticoagulant therapy were enrolled into five age groups (0-6 months, 0.5–2 years, 2–6 years, 6–12 years and 12–18 years) receiving tablet or oral suspension of edoxaban expected to be equivalent to 30 mg or 60 mg in adults. Blood samples for PK and PD analyses were collected within specified time windows. An NLME PK model was used to estimate population parameters.

Results: 66 children were evaluated. The edoxaban plasma concentration peaked between 1 and 3 hours, and declined rapidly until 4-8 hours. In all age groups, PD parameters (prothrombin time, activated partial thromboplastin time and anti-Factor Xa activity) appeared to show a linear relationship versus edoxaban plasma concentrations and were in line with previously acquired adult data. The population CL/F and V/F for a 70 kg patient were estimated to be 42.9 L/h and 198 L, respectively. Across all age groups, the estimated median exposures were within the 0.5- to 1.5-fold of the median AUC in adult patients receiving corresponding doses (30 mg QD for low dose and 60 mg QD for high dose).

Conclusion: Body weight- and age-adjusted, single-dose edoxaban had comparable PK/PD profiles in children across all age groups from 0.008 to 18 years. Both the PK exposure and PK-PD relationships in pediatrics were in line with that observed in adult VTE patients receiving corresponding doses, supporting further evaluation of the dose in pediatric efficacy and safety studies.