Phase 1 Pediatric Pharmacokinetics/Pharmacodynamics (PK/PD) Study

A Phase 1, Open-Label, Single-Dose, Non-Randomized Study to Evaluate Pharmacokinetics and Pharmacodynamics of Edoxaban in Pediatric Patients

This is the first evaluation of edoxaban in pediatric subjects. In this Phase 1 study, a single dose of edoxaban will be given to pediatric subjects who require anticoagulant therapy to see what the body does to the drug (pharmacokinetics) and what the drug does to the body (pharmacodynamics), and to compare if these effects are similar to those observed in adults.

Phase 1, open-label, multiple-center study in pediatric patients from 0 to < 18 years of age. Patients will receive a single dose of edoxaban to match either the 30 mg (low dose) or the 60 mg (high dose) exposure in adults. Exact doses will be selected during the study on the basis of PK modeling of emerging data. If unanticipated exposures are observed, the target doses may be modified to best match expected exposure response relationships observed in adults.

Enrollment in the study will start with the low dose, highest age group (adolescents) and will continue from low to high dose in each age group and from higher to lower age groups. Enrollment in the next dose/age cohort will begin after 50% of the subjects have completed the previous dose/age cohort.

Age cohorts and dose groups: (6 participants each in low and high dose groups, for a total of 12 participants per age cohort)

• 12 to < 18 years of age
• 6 to <12 years of age
• 2 to <6 years of age
• 6 months to <2 years of age
• 0 to <6 months of age

Inclusion Criteria:

• Is a pediatric subject requiring anticoagulant therapy
• Will abstain from the use of nonsteroidal anti-inflammatory drugs (such as ibuprofen), and other antiplatelet and anticoagulant agents (except for aspirin) from 24 hours prior to edoxaban dose until after the last PK sample is collected
• Will follow food and concomitant medication restrictions

Exclusion Criteria:

• Any major or clinically relevant unexplained bleeding during prior anticoagulant therapy
• History of abnormal bleeding or coagulation within last 6 months prior to study drug administration
• Renal function with glomerular filtration rate (GFR) less than 50% of normal for age and size
• Malabsorption disorders (e.g., cystic fibrosis or short bowel syndrome)
• Hepatic disease associated with coagulopathy leading to a clinically relevant bleeding risk, alanine transaminase (ALT) > 5 times the upper limit of normal (ULN) or total bilirubin > 2 times the ULN with direct bilirubin > 20% of the total