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

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ClinicalTrials.gov Identifier: NCT02303431
Recruitment Status : Recruiting
First Posted : December 1, 2014
Last Update Posted : March 29, 2021
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

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.

Condition or disease Intervention/treatment Phase
Deep Vein Thrombosis Venous Thromboembolism Drug: Edoxaban low dose Drug: Edoxaban high dose Phase 1

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A Phase 1, Open-Label, Single-Dose, Non-Randomized Study to Evaluate Pharmacokinetics and Pharmacodynamics of Edoxaban in Pediatric Patients
Actual Study Start Date : April 13, 2016
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Edoxaban

Arm Intervention/treatment
Experimental: Cohort 1a
12 to < 18 years of age: edoxaban low dose group
Drug: Edoxaban low dose
Edoxaban low dose

Experimental: Cohort 1b
12 to < 18 years of age: edoxaban high dose group
Drug: Edoxaban high dose
Edoxaban high dose

Experimental: Cohort 2a
6 to < 12 years of age: edoxaban low dose group
Drug: Edoxaban low dose
Edoxaban low dose

Experimental: Cohort 2b
6 to < 12 years of age: edoxaban high dose group
Drug: Edoxaban high dose
Edoxaban high dose

Experimental: Cohort 3a
2 to < 6 years of age: edoxaban low dose group
Drug: Edoxaban low dose
Edoxaban low dose

Experimental: Cohort 3b
2 to < 6 years of age: edoxaban high dose group
Drug: Edoxaban high dose
Edoxaban high dose

Experimental: Cohort 4a
6 months to <2 years of age: edoxaban low dose group
Drug: Edoxaban low dose
Edoxaban low dose

Experimental: Cohort 4b
6 months to <2 years of age: edoxaban high dose group
Drug: Edoxaban high dose
Edoxaban high dose

Experimental: Cohort 5a
0 to 6 months of age: edoxaban low dose group
Drug: Edoxaban low dose
Edoxaban low dose

Experimental: Cohort 5b
0 to 6 months: edoxaban high dose group
Drug: Edoxaban high dose
Edoxaban high dose




Primary Outcome Measures :
  1. Pharmacokinetics (PK)- Apparent systemic clearance (CL/F) [ Time Frame: within 36 hours postdose ]
    A sampling windows approach will be used: 0.25 to 1, 1.5 to 3, 4 to 8, 9 to 14, and 24 to 36 hours postdose (total of 5 blood samplings)

  2. PK- Apparent volume of distribution (V/F) [ Time Frame: within 36 hours postdose ]
    A sampling windows approach will be used: 0.25 to 1, 1.5 to 3, 4 to 8, 9 to 14, and 24 to 36 hours postdose (total of 5 blood samplings)

  3. PK- Area under the concentration-time curve (AUC) for edoxaban and metabolites [ Time Frame: within 36 hours postdose ]
    A sampling windows approach will be used: 0.25 to 1, 1.5 to 3, 4 to 8, 9 to 14, and 24 to 36 hours postdose (total of 5 blood samplings); metabolites include D21-2393, D21-3231, D21-1402, and D21-2135

  4. PK- Metabolite/parent ratios for AUC [ Time Frame: within 36 hours postdose ]
    A sampling windows approach will be used: 0.25 to 1, 1.5 to 3, 4 to 8, 9 to 14, and 24 to 36 hours postdose (total of 5 blood samplings); metabolites include D21-2393, D21-3231, D21-1402, and D21-2135


Secondary Outcome Measures :
  1. Pharmacodynamic (PDy)- Mean prothrombin time (PT) [ Time Frame: Predose and within 36 hours postdose ]
    Predose and immediately after simultaneously scheduled PK blood samples, using a dosing windows approach: 0.25 to 1, 1.5 to 3, 4 to 8, 9 to 14, and 24 to 36 hours postdose (total of 6 blood samplings)

  2. PDy- Mean activated partial thromboplastin time (aPTT) [ Time Frame: Predose and within 36 hours postdose ]
    Predose and immediately after simultaneously scheduled PK blood samples, using a dosing windows approach: 0.25 to 1, 1.5 to 3, 4 to 8, 9 to 14, and 24 to 36 hours postdose (total of 6 blood samplings)

  3. PDy- Mean anti-Factor Xa (FXa) [ Time Frame: Predose and within 36 hours postdose ]
    Predose and immediately after simultaneously scheduled PK blood samples, using a dosing windows approach: 0.25 to 1, 1.5 to 3, 4 to 8, 9 to 14, and 24 to 36 hours postdose (total of 6 blood samplings)

  4. Safety- Number of participants with clinically significant changes in safety assessments [ Time Frame: Predose to Day 10 ]
    Safety assessments: adverse events, physical examination findings, vital signs, clinical laboratory assessments, and urinalysis.


Other Outcome Measures:
  1. Mean palatability score for the liquid formulation on a 100 mm visual analog scale (VAS) [ Time Frame: within 30 minutes after dosing ]
    Bitterness, sweetness, and overall taste or aroma will be assessed by participants receiving the liquid oral suspension or their guardians using visual analog scale (VAS) scores



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02303431


Contacts
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Contact: Daiichi Sankyo Contact for Clinical Trial Information 908-992-6400 CTRinfo@dsi.com

Locations
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Sponsors and Collaborators
Daiichi Sankyo, Inc.
Investigators
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Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
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Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT02303431    
Other Study ID Numbers: DU176b-A-U157
2015-005732-18 ( EudraCT Number )
First Posted: December 1, 2014    Key Record Dates
Last Update Posted: March 29, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (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.
URL: https://vivli.org/ourmember/daiichi-sankyo/
Keywords provided by Daiichi Sankyo, Inc.:
Pediatric
Pharmacokinetics (PK)
Pharmacodynamics (PDy)
Anticoagulant
Safety
Additional relevant MeSH terms:
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Thrombosis
Thromboembolism
Venous Thromboembolism
Venous Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Edoxaban
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants