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

Venous Thromboembolism Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02303431
• Other study ID #: DU176b-A-U157
• Secondary ID: 2015-005732-18
• Status: Completed
• Phase: Phase 1
• Start date: November 5, 2014
• Est. completion date: September 16, 2021

Study information

• Verified date: December 2022
• Source: Daiichi Sankyo, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: September 16, 2021
• Est. primary completion date: September 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Deep Vein Thrombosis
• Thromboembolism
• Thrombosis
• Venous Thromboembolism
• Venous Thrombosis

Intervention

Drug:
• Edoxaban low dose
Edoxaban low dose
• Edoxaban high dose
Edoxaban high dose

Locations

Country	Name	City	State
Canada	McMaster Children's Hospital	Hamilton	Ontario
Canada	Childrens Hospital of Eastern Ontario	Ottawa
France	Hopital Arnaud de Villeneuve	Montpellier
France	CHU Bordeaux - Hopital Haut-Leveque	Pessac
India	Nirmal Hospital Pvt. Ltd	Gujrat
India	Institute of Child Health	Kolkata
India	Christian Medical College and Hospital	Ludhiana
Italy	Istituto Giannina Gaslini - UOSD Emostasi e Trombosi	Genova
Italy	A O Universita degli Studi di Padova ; Dipartimento di Salute della Donna e del Bambino-Universita di Padova	Padova
Italy	Bambino Gesu Hospital	Rome
Lebanon	Hotel Dieu De France	Beirut
Lebanon	Hammoud Hospital University Medical Center	Saida
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Universitario Reina Sofia	Cordoba
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Araba	Vitoria Gasteiz
Turkey	Ege University Medical Faculty - Department of Pediatric Hematology	Izmir
United Kingdom	Leeds General Infirmary	Leeds
United Kingdom	Glenfield Hospital	Leicester
United Kingdom	Guy's and St Thomas Hospital NHS Trust	London
United Kingdom	Royal Brompton Hospital	London
United Kingdom	Southampton General Hospital	Southampton
United States	Ann and Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	University Hospitals Case Medical Center - Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	University of Colorado Denver	Denver	Colorado
United States	Duke University Medical Center (DUMC)	Durham	North Carolina
United States	Indiana Hemophilia and Thrombosis Center	Indianapolis	Indiana
United States	University of California, Los Angeles (UCLA)	Los Angeles	California
United States	University of Louisville ; Kosair Charities Pediatric Clincial Research Unit	Louisville	Kentucky
United States	St. Jude Children's Research Hospital, Inc.	Memphis	Tennessee
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Lucile Packard Children's Hospital Stanford University	Palo Alto	California
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Hasbro Children's Hospital	Providence	Rhode Island

Sponsors (1)

Lead Sponsor	Collaborator
Daiichi Sankyo, Inc.

Countries where clinical trial is conducted

United States,  Canada,  France,  India,  Italy,  Lebanon,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS)	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.	Baseline up to 30 minutes post-dose
Primary	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.	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
Primary	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.	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	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.	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
Secondary	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.	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
Secondary	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.	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