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

Daiichi Sankyo66 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Deep Vein Thrombosis Venous Thromboembolism

Interventions

Edoxaban low doseDRUG

Edoxaban low dose

Edoxaban high doseDRUG

Edoxaban high dose

Eligibility

Sex: ALLMin age: 0 YearsMax age: 18 Years

Medical Language ↔ Plain English

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

Locations (35)

Outcomes

Primary Outcomes

Pharmacokinetic Parameter of Apparent Systemic Clearance (CL/F)

A model-based pooled population pharmacokinetic (PK) method was used to estimate systemic clearance (CL/F). As prespecified in the protocol, arms were pooled due to sparse PK samples being collected. the median PK estimate is reported in all participants at a total of 5 blood samplings.

Time frame: 0.25 to 1 hours, 1.5 to 3 hours, 4 to 8 hours, 9 to 14 hours, and 24 to 36 hours post-dose

Pharmacokinetic Parameter of Apparent Volume of Distribution (V/F)

A model-based pooled population pharmacokinetic (PK) method was used to estimate apparent volume of distribution (V/F). As prespecified in the protocol, arms were pooled due to sparse PK samples being collected. the median PK estimate is reported in all participants at a total of 5 blood samplings.

Time frame: 0.25 to 1 hours, 1.5 to 3 hours, 4 to 8 hours, 9 to 14 hours, and 24 to 36 hours post-dose

Secondary Outcomes

Pharmacodynamic Parameter Mean Prothrombin Time (PT)

Descriptive statistics were used to assess Mean Prothrombin Time (PT) by cohort at a total of 6 blood samplings.

Time frame: Pre-dose and 0.25 to 1 hours (except for Cohorts 4a, 4b, 5a, and 5b, 0.5 to 2 hours), 1.5 to 3 hours, 4 to 8 hours, 9 to 14 hours, and 24 to 36 hours post-dose

Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT)

Descriptive statistics were used to assess Mean Activated Partial Thromboplastin Time by cohort for a total of 6 blood samplings.

Time frame: Pre-dose and 0.25 to 1 hours (except for Cohorts 4a, 4b, 5a, and 5b, 0.5 to 2 hours), 1.5 to 3 hours, 4 to 8 hours, 9 to 14 hours, and 24 to 36 hours post-dose

Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa)

Descriptive statistics were used to assess Mean Anti-Factor Xa (FXa) by cohort for a total of 6 blood samplings.

Data from ClinicalTrials.gov

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