Phase 1 Pediatric Pharmacokinetics/Pharmacodynamics (PK/PD) Study
- Conditions
- Venous ThromboembolismDeep Vein Thrombosis
- Interventions
- Registration Number
- NCT02303431
- Lead Sponsor
- Daiichi Sankyo
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 66
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cohort 1b Edoxaban high dose 12 to \< 18 years of age: edoxaban high dose group Cohort 2b Edoxaban high dose 6 to \< 12 years of age: edoxaban high dose group Cohort 1a Edoxaban low dose 12 to \< 18 years of age: edoxaban low dose group Cohort 2a Edoxaban low dose 6 to \< 12 years of age: edoxaban low dose group Cohort 4a Edoxaban low dose 6 months to \<2 years of age: edoxaban low dose group Cohort 3b Edoxaban high dose 2 to \< 6 years of age: edoxaban high dose group Cohort 5b Edoxaban high dose 0 to 6 months: edoxaban high dose group Cohort 3a Edoxaban low dose 2 to \< 6 years of age: edoxaban low dose group Cohort 5a Edoxaban low dose 0 to 6 months of age: edoxaban low dose group Cohort 4b Edoxaban high dose 6 months to \<2 years of age: edoxaban high dose group
- Primary Outcome Measures
Name Time Method Pharmacokinetic Parameter of Apparent Systemic Clearance (CL/F) 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.
Pharmacokinetic Parameter of Apparent Volume of Distribution (V/F) 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 Outcome Measures
Name Time Method 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 Descriptive statistics were used to assess Mean Activated Partial Thromboplastin Time by cohort for a total of 6 blood samplings.
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 Descriptive statistics were used to assess Mean Prothrombin Time (PT) by cohort at a total of 6 blood samplings.
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 Descriptive statistics were used to assess Mean Anti-Factor Xa (FXa) by cohort for a total of 6 blood samplings.
Trial Locations
- Locations (35)
Hopital Arnaud de Villeneuve
🇫🇷Montpellier, France
McMaster Children's Hospital
🇨🇦Hamilton, Ontario, Canada
Institute of Child Health
🇮🇳Kolkata, India
Glenfield Hospital
🇬🇧Leicester, United Kingdom
Guy's and St Thomas Hospital NHS Trust
🇬🇧London, United Kingdom
Southampton General Hospital
🇬🇧Southampton, United Kingdom
Ann and Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Nirmal Hospital Pvt. Ltd
🇮🇳Gujrat, India
University of Colorado Denver
🇺🇸Denver, Colorado, United States
University of California, Los Angeles (UCLA)
🇺🇸Los Angeles, California, United States
Lucile Packard Children's Hospital Stanford University
🇺🇸Palo Alto, California, United States
Indiana Hemophilia and Thrombosis Center
🇺🇸Indianapolis, Indiana, United States
University of Louisville ; Kosair Charities Pediatric Clincial Research Unit
🇺🇸Louisville, Kentucky, United States
Duke University Medical Center (DUMC)
🇺🇸Durham, North Carolina, United States
Childrens Hospital of Eastern Ontario
🇨🇦Ottawa, Canada
Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
St. Jude Children's Research Hospital, Inc.
🇺🇸Memphis, Tennessee, United States
CHU Bordeaux - Hopital Haut-Leveque
🇫🇷Pessac, France
University Hospitals Case Medical Center - Rainbow Babies and Children's Hospital
🇺🇸Cleveland, Ohio, United States
The Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Christian Medical College and Hospital
🇮🇳Ludhiāna, India
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, Italy
Hotel Dieu De France
🇱🇧Beirut, Lebanon
Hammoud Hospital University Medical Center
🇱🇧Saida, Lebanon
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario Reina Sofia
🇪🇸Cordoba, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Ege University Medical Faculty - Department of Pediatric Hematology
🇹🇷Izmir, Turkey
Hospital Universitario Araba
🇪🇸Vitoria Gasteiz, Spain
Leeds General Infirmary
🇬🇧Leeds, United Kingdom
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Royal Brompton Hospital
🇬🇧London, United Kingdom
Hasbro Children's Hospital
🇺🇸Providence, Rhode Island, United States