Deep Vein ThrombosisPhase 1NCT02303431
Phase 1 Pediatric Pharmacokinetics/Pharmacodynamics (PK/PD) Study
A Phase 1 study testing Edoxaban low dose and Edoxaban high dose in people with Deep Vein Thrombosis and Venous Thromboembolism, run by Daiichi Sankyo at 35 sites in 9 countries.
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… Read more about this study
- Who is it for?
- Ages 0 to 18 years
- Conditions the study is for
- Deep Vein Thrombosis, Venous Thromboembolism
- What is being tested?
- Edoxaban low dose and Edoxaban high dose
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 35 sitesin 9 countries
- Study dates
- 5 Nov 2014to 16 Sep 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
35 sites in 9 countries.
35 sites in 9 countries
United States12 sites
Ann and Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
University Hospitals Case Medical Center - Rainbow Babies and Children's Hospital
Cleveland, Ohio, 44106
University of Colorado Denver
Denver, Colorado, 80045
Duke University Medical Center (DUMC)
Durham, North Carolina, 22710
Indiana Hemophilia and Thrombosis Center
Indianapolis, Indiana, 46260
University of California, Los Angeles (UCLA)
Los Angeles, California, 90095
University of Louisville ; Kosair Charities Pediatric Clincial Research Unit
Louisville, Kentucky, 40202
St. Jude Children's Research Hospital, Inc.
Memphis, Tennessee, 38105
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Hasbro Children's Hospital
Providence, Rhode Island, 02903
Spain5 sites
Hospital Universitario Vall d'Hebron
Barcelona, 8035
Hospital Universitario Reina Sofia
Córdoba, 14004
Hospital Clinico San Carlos
Madrid, 28040
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitario Araba
Vitoria-Gasteiz, 01010
United Kingdom5 sites
Leeds General Infirmary
Leeds, LS1 3EB
Glenfield Hospital
Leicester, LE3 9QP
Guy's and St Thomas Hospital NHS Trust
London, SE1 7EH
Royal Brompton Hospital
London, SW3 6NP
Southampton General Hospital
Southampton, SO16 6YD
India3 sites
Nirmal Hospital Pvt. Ltd
Gujrāt, 395002
Institute of Child Health
Kolkata, 700017
Christian Medical College and Hospital
Ludhiāna, 141008
Italy3 sites
Istituto Giannina Gaslini - UOSD Emostasi e Trombosi
Genova, 16148
A O Universita degli Studi di Padova ; Dipartimento di Salute della Donna e del Bambino-Universita di Padova
Padova, 35127
Bambino Gesu Hospital
Rome, 165
Canada2 sites
McMaster Children's Hospital
Hamilton, Ontario, L8N3Z5
Childrens Hospital of Eastern Ontario
Ottawa, K1H8L1
France2 sites
Hopital Arnaud de Villeneuve
Montpellier, 34295
CHU Bordeaux - Hopital Haut-Leveque
Pessac, 33604
Lebanon2 sites
Hotel Dieu De France
Beirut, BP 165191
Hammoud Hospital University Medical Center
Saida, 1600
Turkey (Türkiye)1 site
Ege University Medical Faculty - Department of Pediatric Hematology
Izmir, 35040
About this study
Official title: A Phase 1, Open-Label, Single-Dose, Non-Randomized Study to Evaluate Pharmacokinetics and Pharmacodynamics of Edoxaban in Pediatric Patients
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.
Read the 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
- Conditions
- Deep Vein Thrombosis, Venous Thromboembolism
- Being tested
- Edoxaban low dose, Edoxaban high dose
- Keywords
- Pediatric, Pharmacokinetics (PK), Pharmacodynamics (PDy), Anticoagulant, Safety
- Medical subject headings
- Venous Thrombosis, Venous Thromboembolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Edoxaban low doseDrug
Edoxaban low dose
Edoxaban high doseDrug
Edoxaban high dose
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1a | Experimental | 12 to < 18 years of age: edoxaban low dose group Receives: Drug: Edoxaban low dose |
| Cohort 1b | Experimental | 12 to < 18 years of age: edoxaban high dose group Receives: Drug: Edoxaban high dose |
| Cohort 2a | Experimental | 6 to < 12 years of age: edoxaban low dose group Receives: Drug: Edoxaban low dose |
| Cohort 2b | Experimental | 6 to < 12 years of age: edoxaban high dose group Receives: Drug: Edoxaban high dose |
| Cohort 3a | Experimental | 2 to < 6 years of age: edoxaban low dose group Receives: Drug: Edoxaban low dose |
| Cohort 3b | Experimental | 2 to < 6 years of age: edoxaban high dose group Receives: Drug: Edoxaban high dose |
| Cohort 4a | Experimental | 6 months to <2 years of age: edoxaban low dose group Receives: Drug: Edoxaban low dose |
| Cohort 4b | Experimental | 6 months to <2 years of age: edoxaban high dose group Receives: Drug: Edoxaban high dose |
| Cohort 5a | Experimental | 0 to 6 months of age: edoxaban low dose group Receives: Drug: Edoxaban low dose |
| Cohort 5b | Experimental | 0 to 6 months: edoxaban high dose group Receives: Drug: Edoxaban high dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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)
Descriptive statistics were used to assess Mean Prothrombin Time (PT) by cohort at a total of 6 blood samplings.
Measured: 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)
Descriptive statistics were used to assess Mean Activated Partial Thromboplastin Time by cohort for a total of 6 blood samplings.
Measured: 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)
Descriptive statistics were used to assess Mean Anti-Factor Xa (FXa) by cohort for a total of 6 blood samplings.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2014 (estimated)
- Study start5 Nov 2014
- Primary completion16 Sep 2021
- Study completion16 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Deep Vein ThrombosisStudies of the same condition, open and under way.
- More trials run by Daiichi SankyoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Global Clinical Leader, Study director, Daiichi Sankyo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02303431
- Sponsor's protocol ID
- DU176b-A-U157
- Other IDs
- 2015-005732-18, 2015
- Status last verified
- Dec 2022
- First submitted
- 10 Oct 2014
- Last updated
- 11 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: 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/
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, Single-Dose, Non-Randomized Study to Evaluate Pharmacokinetics and Pharmacodynamics of Edoxaban in Pediatric Patients
- ClinicalTrials.gov ID
- NCT02303431
- Acronym / sponsor ID
- DU176b-A-U157
- Conditions
- Deep Vein Thrombosis, Venous Thromboembolism
- Keywords
- Pediatric, Pharmacokinetics (PK), Pharmacodynamics (PDy), Anticoagulant, Safety
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Daiichi SankyoIndustry (pharma, biotech, devices)
- Study start
- 5 Nov 2014 (actual)
- Primary completion
- 16 Sep 2021 (actual)
- Study completion
- 16 Sep 2021 (actual)
- First posted
- 1 Dec 2014 (estimated)
- Results
- Posted 11 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| Cohort 1a | Experimental | Drug: Edoxaban low dose12 to < 18 years of age: edoxaban low dose group |
| Cohort 1b | Experimental | Drug: Edoxaban high dose12 to < 18 years of age: edoxaban high dose group |
| Cohort 2a | Experimental | Drug: Edoxaban low dose6 to < 12 years of age: edoxaban low dose group |
| Cohort 2b | Experimental | Drug: Edoxaban high dose6 to < 12 years of age: edoxaban high dose group |
| Cohort 3a | Experimental | Drug: Edoxaban low dose2 to < 6 years of age: edoxaban low dose group |
| Cohort 3b | Experimental | Drug: Edoxaban high dose2 to < 6 years of age: edoxaban high dose group |
| Cohort 4a | Experimental | Drug: Edoxaban low dose6 months to <2 years of age: edoxaban low dose group |
| Cohort 4b | Experimental | Drug: Edoxaban high dose6 months to <2 years of age: edoxaban high dose group |
| Cohort 5a | Experimental | Drug: Edoxaban low dose0 to 6 months of age: edoxaban low dose group |
| Cohort 5b | Experimental | Drug: Edoxaban high dose0 to 6 months: edoxaban high dose group |
Who may qualify
- Ages
- 0 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Edoxaban low doseEdoxaban low dose | Drug | Cohort 1a, Cohort 2a, Cohort 3a, Cohort 4a, Cohort 5a |
| Edoxaban high doseEdoxaban high dose | Drug | Cohort 1b, Cohort 2b, Cohort 3b, Cohort 4b, Cohort 5b |
Primary outcome
Pharmacokinetic Parameter of Apparent Systemic Clearance (CL/F)
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
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)
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
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.
3 secondary outcomes
Pharmacodynamic Parameter Mean Prothrombin Time (PT)
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
Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT)
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
Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa)
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. 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/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Global Clinical Leader study director
Daiichi Sankyo
35 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Edoxaban low dose and Edoxaban high dose in people with Deep Vein Thrombosis and Venous Thromboembolism, run by Daiichi Sankyo at 35 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in United States, Spain, United Kingdom, India, Italy and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetic Parameter of Apparent Systemic Clearance (CL/F) (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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Oct 2023.