Clinical trial NCT02303431: Phase 1 Pediatric Pharmacokinetics/Pharmacodynamics (PK/PD) Study
Official title: A Phase 1, Open-Label, Single-Dose, Non-Randomized Study to Evaluate Pharmacokinetics and Pharmacodynamics of Edoxaban in Pediatric Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Deep Vein Thrombosis
Venous Thromboembolism
Keywords: Pediatric
Pharmacokinetics (PK)
Pharmacodynamics (PDy)
Anticoagulant
Safety
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2014-12-01
Enrollment: 66
Sex: ALL
Minimum age (years): 0
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief 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.

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetic Parameter of Apparent Systemic Clearance (CL/F)
timeFrame: 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
measure: Pharmacokinetic Parameter of Apparent Volume of Distribution (V/F)
timeFrame: 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:
measure: Pharmacodynamic Parameter Mean Prothrombin Time (PT)
timeFrame: 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
measure: Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT)
timeFrame: 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
measure: Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa)
timeFrame: 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
Other outcomes:
measure: Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS)
timeFrame: Baseline up to 30 minutes post-dose
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles (UCLA)
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital Stanford University
state: California
city: Denver
country: United States
facility: University of Colorado Denver
state: Colorado
city: Chicago
country: United States
facility: Ann and Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Hemophilia and Thrombosis Center
state: Indiana
city: Louisville
country: United States
facility: University of Louisville ; Kosair Charities Pediatric Clincial Research Unit
state: Kentucky
city: Durham
country: United States
facility: Duke University Medical Center (DUMC)
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center - Rainbow Babies and Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Providence
country: United States
facility: Hasbro Children's Hospital
state: Rhode Island
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital, Inc.
state: Tennessee
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
city: Hamilton
country: Canada
facility: McMaster Children's Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Childrens Hospital of Eastern Ontario
city: Montpellier
country: France
facility: Hopital Arnaud de Villeneuve
city: Pessac
country: France
facility: CHU Bordeaux - Hopital Haut-Leveque
city: Gujrat
country: India
facility: Nirmal Hospital Pvt. Ltd
city: Kolkata
country: India
facility: Institute of Child Health
city: Ludhiāna
country: India
facility: Christian Medical College and Hospital
city: Genova
country: Italy
facility: Istituto Giannina Gaslini - UOSD Emostasi e Trombosi
city: Padova
country: Italy
facility: A O Universita degli Studi di Padova ; Dipartimento di Salute della Donna e del Bambino-Universita di Padova
city: Rome
country: Italy
facility: Bambino Gesu Hospital
city: Beirut
country: Lebanon
facility: Hotel Dieu De France
city: Saida
country: Lebanon
facility: Hammoud Hospital University Medical Center
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Vitoria Gasteiz
country: Spain
facility: Hospital Universitario Araba
city: Izmir
country: Turkey
facility: Ege University Medical Faculty - Department of Pediatric Hematology
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: Leicester
country: United Kingdom
facility: Glenfield Hospital
city: London
country: United Kingdom
facility: Guy's and St Thomas Hospital NHS Trust
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: