search
Back to results

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

Primary Purpose

Deep Vein Thrombosis, Venous Thromboembolism

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Edoxaban low dose
Edoxaban high dose
Sponsored by
Daiichi Sankyo, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Deep Vein Thrombosis focused on measuring Pediatric, Pharmacokinetics (PK), Pharmacodynamics (PDy), Anticoagulant, Safety

Eligibility Criteria

0 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California, Los Angeles (UCLA)
  • Lucile Packard Children's Hospital Stanford University
  • University of Colorado Denver
  • Ann and Robert H. Lurie Children's Hospital of Chicago
  • Indiana Hemophilia and Thrombosis Center
  • University of Louisville ; Kosair Charities Pediatric Clincial Research Unit
  • Duke University Medical Center (DUMC)
  • University Hospitals Case Medical Center - Rainbow Babies and Children's Hospital
  • The Children's Hospital of Philadelphia
  • Hasbro Children's Hospital
  • St. Jude Children's Research Hospital, Inc.
  • Children's Hospital of Wisconsin
  • McMaster Children's Hospital
  • Childrens Hospital of Eastern Ontario
  • Hopital Arnaud de Villeneuve
  • CHU Bordeaux - Hopital Haut-Leveque
  • Nirmal Hospital Pvt. Ltd
  • Institute of Child Health
  • Christian Medical College and Hospital
  • Istituto Giannina Gaslini - UOSD Emostasi e Trombosi
  • A O Universita degli Studi di Padova ; Dipartimento di Salute della Donna e del Bambino-Universita di Padova
  • Bambino Gesu Hospital
  • Hotel Dieu De France
  • Hammoud Hospital University Medical Center
  • Hospital Universitario Vall d'Hebron
  • Hospital Universitario Reina Sofia
  • Hospital Clinico San Carlos
  • Hospital Universitario La Paz
  • Hospital Universitario Araba
  • Ege University Medical Faculty - Department of Pediatric Hematology
  • Leeds General Infirmary
  • Glenfield Hospital
  • Guy's and St Thomas Hospital NHS Trust
  • Royal Brompton Hospital
  • Southampton General Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1a

Cohort 1b

Cohort 2a

Cohort 2b

Cohort 3a

Cohort 3b

Cohort 4a

Cohort 4b

Cohort 5a

Cohort 5b

Arm Description

12 to < 18 years of age: edoxaban low dose group

12 to < 18 years of age: edoxaban high dose group

6 to < 12 years of age: edoxaban low dose group

6 to < 12 years of age: edoxaban high dose group

2 to < 6 years of age: edoxaban low dose group

2 to < 6 years of age: edoxaban high dose group

6 months to <2 years of age: edoxaban low dose group

6 months to <2 years of age: edoxaban high dose group

0 to 6 months of age: edoxaban low dose group

0 to 6 months: edoxaban high dose group

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
October 10, 2014
Last Updated
December 8, 2022
Sponsor
Daiichi Sankyo, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT02303431
Brief Title
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

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
November 5, 2014 (Actual)
Primary Completion Date
September 16, 2021 (Actual)
Study Completion Date
September 16, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Daiichi Sankyo, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Deep Vein Thrombosis, Venous Thromboembolism
Keywords
Pediatric, Pharmacokinetics (PK), Pharmacodynamics (PDy), Anticoagulant, Safety

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
66 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1a
Arm Type
Experimental
Arm Description
12 to < 18 years of age: edoxaban low dose group
Arm Title
Cohort 1b
Arm Type
Experimental
Arm Description
12 to < 18 years of age: edoxaban high dose group
Arm Title
Cohort 2a
Arm Type
Experimental
Arm Description
6 to < 12 years of age: edoxaban low dose group
Arm Title
Cohort 2b
Arm Type
Experimental
Arm Description
6 to < 12 years of age: edoxaban high dose group
Arm Title
Cohort 3a
Arm Type
Experimental
Arm Description
2 to < 6 years of age: edoxaban low dose group
Arm Title
Cohort 3b
Arm Type
Experimental
Arm Description
2 to < 6 years of age: edoxaban high dose group
Arm Title
Cohort 4a
Arm Type
Experimental
Arm Description
6 months to <2 years of age: edoxaban low dose group
Arm Title
Cohort 4b
Arm Type
Experimental
Arm Description
6 months to <2 years of age: edoxaban high dose group
Arm Title
Cohort 5a
Arm Type
Experimental
Arm Description
0 to 6 months of age: edoxaban low dose group
Arm Title
Cohort 5b
Arm Type
Experimental
Arm Description
0 to 6 months: edoxaban high dose group
Intervention Type
Drug
Intervention Name(s)
Edoxaban low dose
Intervention Description
Edoxaban low dose
Intervention Type
Drug
Intervention Name(s)
Edoxaban high dose
Intervention Description
Edoxaban high dose
Primary Outcome Measure Information:
Title
Pharmacokinetic Parameter of Apparent Systemic Clearance (CL/F)
Description
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
Title
Pharmacokinetic Parameter of Apparent Volume of Distribution (V/F)
Description
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 Outcome Measure Information:
Title
Pharmacodynamic Parameter Mean Prothrombin Time (PT)
Description
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
Title
Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT)
Description
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
Title
Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa)
Description
Descriptive statistics were used to assess Mean Anti-Factor Xa (FXa) 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
Other Pre-specified Outcome Measures:
Title
Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS)
Description
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.
Time Frame
Baseline up to 30 minutes post-dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
0 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Global Clinical Leader
Organizational Affiliation
Daiichi Sankyo, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
University of California, Los Angeles (UCLA)
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Lucile Packard Children's Hospital Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
University of Colorado Denver
City
Denver
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Ann and Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Indiana Hemophilia and Thrombosis Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
University of Louisville ; Kosair Charities Pediatric Clincial Research Unit
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Duke University Medical Center (DUMC)
City
Durham
State/Province
North Carolina
ZIP/Postal Code
22710
Country
United States
Facility Name
University Hospitals Case Medical Center - Rainbow Babies and Children's Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
The Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Hasbro Children's Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
St. Jude Children's Research Hospital, Inc.
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Facility Name
Children's Hospital of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
McMaster Children's Hospital
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N3Z5
Country
Canada
Facility Name
Childrens Hospital of Eastern Ontario
City
Ottawa
ZIP/Postal Code
K1H8L1
Country
Canada
Facility Name
Hopital Arnaud de Villeneuve
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
CHU Bordeaux - Hopital Haut-Leveque
City
Pessac
ZIP/Postal Code
33604
Country
France
Facility Name
Nirmal Hospital Pvt. Ltd
City
Gujrat
ZIP/Postal Code
395002
Country
India
Facility Name
Institute of Child Health
City
Kolkata
ZIP/Postal Code
700017
Country
India
Facility Name
Christian Medical College and Hospital
City
Ludhiāna
ZIP/Postal Code
141008
Country
India
Facility Name
Istituto Giannina Gaslini - UOSD Emostasi e Trombosi
City
Genova
ZIP/Postal Code
16148
Country
Italy
Facility Name
A O Universita degli Studi di Padova ; Dipartimento di Salute della Donna e del Bambino-Universita di Padova
City
Padova
ZIP/Postal Code
35127
Country
Italy
Facility Name
Bambino Gesu Hospital
City
Rome
ZIP/Postal Code
165
Country
Italy
Facility Name
Hotel Dieu De France
City
Beirut
ZIP/Postal Code
BP 165191
Country
Lebanon
Facility Name
Hammoud Hospital University Medical Center
City
Saida
ZIP/Postal Code
1600
Country
Lebanon
Facility Name
Hospital Universitario Vall d'Hebron
City
Barcelona
ZIP/Postal Code
8035
Country
Spain
Facility Name
Hospital Universitario Reina Sofia
City
Cordoba
ZIP/Postal Code
14004
Country
Spain
Facility Name
Hospital Clinico San Carlos
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Hospital Universitario La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Hospital Universitario Araba
City
Vitoria Gasteiz
ZIP/Postal Code
01010
Country
Spain
Facility Name
Ege University Medical Faculty - Department of Pediatric Hematology
City
Izmir
ZIP/Postal Code
35040
Country
Turkey
Facility Name
Leeds General Infirmary
City
Leeds
ZIP/Postal Code
LS1 3EB
Country
United Kingdom
Facility Name
Glenfield Hospital
City
Leicester
ZIP/Postal Code
LE3 9QP
Country
United Kingdom
Facility Name
Guy's and St Thomas Hospital NHS Trust
City
London
ZIP/Postal Code
SE1 7EH
Country
United Kingdom
Facility Name
Royal Brompton Hospital
City
London
ZIP/Postal Code
SW3 6NP
Country
United Kingdom
Facility Name
Southampton General Hospital
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
IPD Sharing Time Frame
Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
IPD Sharing Access Criteria
Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
IPD Sharing URL
https://vivli.org/ourmember/daiichi-sankyo/

Learn more about this trial

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

We'll reach out to this number within 24 hrs