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

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