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

NCT02303431 | Completed Phase 1 Results DMC

• 2 other identifiers: DU176b-A-U1572015-005732-18
• Study Type: interventional
• Target: 66
• Locations: 9 countries
• Sites: 35

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.

Conditions

Deep Vein Thrombosis; Venous Thromboembolism

Keywords

Pediatric; Pharmacokinetics (PK); Pharmacodynamics (PDy); Anticoagulant; Safety

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (3)

• Pharmacodynamic Parameter Mean Prothrombin Time (PT)

  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)

  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)

  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 (1)

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

  Baseline up to 30 minutes post-dose

Study Arms (10)

Cohort 1a

EXPERIMENTAL

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

Drug: Edoxaban low dose

Cohort 1b

EXPERIMENTAL

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

Drug: Edoxaban high dose

Cohort 2a

EXPERIMENTAL

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

Drug: Edoxaban low dose

Cohort 2b

EXPERIMENTAL

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

Drug: Edoxaban high dose

Cohort 3a

EXPERIMENTAL

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

Drug: Edoxaban low dose

Cohort 3b

EXPERIMENTAL

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

Drug: Edoxaban high dose

Cohort 4a

EXPERIMENTAL

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

Drug: Edoxaban low dose

Cohort 4b

EXPERIMENTAL

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

Drug: Edoxaban high dose

Cohort 5a

EXPERIMENTAL

0 to 6 months of age: edoxaban low dose group

Drug: Edoxaban low dose

Cohort 5b

EXPERIMENTAL

0 to 6 months: edoxaban high dose group

Drug: Edoxaban high dose

Interventions

Edoxaban low dose DRUG

Edoxaban low dose

Cohort 1a; Cohort 2a; Cohort 3a; Cohort 4a; Cohort 5a

Edoxaban high dose DRUG

Edoxaban high dose

Cohort 1b; Cohort 2b; Cohort 3b; Cohort 4b; Cohort 5b

Eligibility Criteria

• Age: 0 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (35)

University of California, Los Angeles (UCLA)

Los Angeles, California, 90095, United States

Location

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, 94304, United States

Location

University of Colorado Denver

Denver, Colorado, 80045, United States

Location

Ann and Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, 46260, United States

Location

University of Louisville ; Kosair Charities Pediatric Clincial Research Unit

Louisville, Kentucky, 40202, United States

Location

Duke University Medical Center (DUMC)

Durham, North Carolina, 22710, United States

Location

University Hospitals Case Medical Center - Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Hasbro Children's Hospital

Providence, Rhode Island, 02903, United States

Location

St. Jude Children's Research Hospital, Inc.

Memphis, Tennessee, 38105, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

McMaster Children's Hospital

Hamilton, Ontario, L8N3Z5, Canada

Location

Childrens Hospital of Eastern Ontario

Ottawa, K1H8L1, Canada

Location

Hopital Arnaud de Villeneuve

Montpellier, 34295, France

Location

CHU Bordeaux - Hopital Haut-Leveque

Pessac, 33604, France

Location

Nirmal Hospital Pvt. Ltd

Gujrāt, 395002, India

Location

Institute of Child Health

Kolkata, 700017, India

Location

Christian Medical College and Hospital

Ludhiāna, 141008, India

Location

Istituto Giannina Gaslini - UOSD Emostasi e Trombosi

Genova, 16148, Italy

Location

A O Universita degli Studi di Padova ; Dipartimento di Salute della Donna e del Bambino-Universita di Padova

Padua, 35127, Italy

Location

Bambino Gesu Hospital

Rome, 165, Italy

Location

Hotel Dieu De France

Beirut, BP 165191, Lebanon

Location

Hammoud Hospital University Medical Center

Saida, 1600, Lebanon

Location

Hospital Universitario Vall d'Hebron

Barcelona, 8035, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14004, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Araba

Vitoria-Gasteiz, 01010, Spain

Location

Ege University Medical Faculty - Department of Pediatric Hematology

Izmir, 35040, Turkey (Türkiye)

Location

Leeds General Infirmary

Leeds, LS1 3EB, United Kingdom

Location

Glenfield Hospital

Leicester, LE3 9QP, United Kingdom

Location

Guy's and St Thomas Hospital NHS Trust

London, SE1 7EH, United Kingdom

Location

Royal Brompton Hospital

London, SW3 6NP, United Kingdom

Location

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

MeSH Terms

Conditions

Venous Thrombosis; Venous Thromboembolism

Interventions

edoxaban

Condition Hierarchy (Ancestors)

Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Thromboembolism

Results Point of Contact

• Title: Contact for Clinical Trial Information
• Organization: Daiichi Sankyo, Inc.

CTRinfo@dsi.com

908-992-6400

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2014
• First Posted: December 1, 2014
• Study Start: November 5, 2014
• Primary Completion: September 16, 2021
• Study Completion: September 16, 2021
• Last Updated: October 11, 2023
• Results First Posted: October 11, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• 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.
• 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.

Locations

CA (2); ES (5); IN (3); US (12); IT (3); FR (2); LE (2); TU (1); GB (5)