Skip to main content
OpenTrials
Completed

NCT Number: NCT02303431

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Deep Vein Thrombosis Cardiovascular Diseases Embolism and Thrombosis Thromboembolism Thrombosis Vascular Diseases Venous Thromboembolism Venous Thrombosis

Age range

0 year–18 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

McMaster Children's Hospital, Hamilton, Ontario, Canada

Loading trial locations.

About this 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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Edoxaban low dose

Drug

Edoxaban low dose

Edoxaban high dose

Drug

Edoxaban high dose

Primary outcomes

  1. Pharmacokinetic Parameter of Apparent Systemic Clearance (CL/F)

    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

    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.

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

    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

    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.

Secondary outcomes

  1. Pharmacodynamic Parameter Mean Prothrombin Time (PT)

    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

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

  2. Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT)

    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

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

  3. Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa)

    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

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

Other outcomes

  1. Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS)

    Time frame: Baseline up to 30 minutes post-dose

    Overall palatability, bitterness, sweetness, and overall taste or aroma were assessed by participants (or guardians) receiving the liquid oral suspension where each subscale used a 100 mm visual analog scale (VAS), where a 0 score corresponded to a sad face and indicated a low palatability, bitter (sharp, pungent taste or smell), not sweet, and no aroma score (eg, patients not pleased; worse outcome in terms of palatability) and a 100 score corresponded to a happy face and indicated a high palatability, not bitter, very sweet, very tasty, and high aroma score (eg, patients were pleased; best outcome in terms of palatability). Patients who were old enough scored the VAS themselves. For younger children, the parents provided this information, if possible. For the youngest children, there was free text input available to provide information on whether the patient spat it out or may not have liked the flavor, etc.

Sponsors and collaborators

Lead sponsor

Daiichi Sankyo

Industry

Registry information

Official study title

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

Important dates

Study start
2014
Primary completion
2021
Study completion
2021
First posted
Dec 1, 2014
Registry last updated
Oct 11, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.