Health Condition 1: D65-D69- Coagulation defects, purpura and other hemorrhagic conditions
Conditions
Interventions
Intervention1: Edoxaban
Treatment arm: Patients will be dosed orally with a single dose of edoxaban on Day 1. Patients in the
12 to 18 years of age cohort will be dosed with multiples of edoxaban tab
Cohorts 2a/2b: 60-mL water
Cohorts 3a/3b: 40-mL water
Cohorts 4a/4b: 10-mL water
Cohorts 5a/5b: 10-mL water).
In each age cohort, weight-adjusted doses will be selected to elicit target exposures
comparable to those achieved from adult doses of 30 mg (low dose) or 60 mg (high
dose
Sponsors
DAIICHI SANKYO INC
Medpace Clinical Research India Pvt Ltd
Eligibility
Inclusion criteria
Inclusion criteria: -Patients who are at risk of thromboembolic events (e.g., patients with thrombophilia, congenital heart disease, presence of a central venous catheter); - Patients who are completing their standard-of-care anticoagulatory therapy.Note that minimum time from the last dose of the standard of careanticoagulant medication and the dose of the study drug should be at least6 hours for unfractionated heparin; 24 hours for vitamin K antagonists(e.g., warfarin) and any other anticoagulants. Note: Before edoxabantreatment, all patients who receive vitamin K antagonists must have aninternational normalization ratio (INR) value 2.0, the patientâ??s INR should be monitored until it is -Patients with cardiac conditions who may require anticoagulation therapy; or -Patients with sickle cell disease who may require anticoagulation therapy. 1. Able to provide written informed assents (patients, when applicable) and ICFs (signed by parent/legal guardian) prior to participating in the study 2. Male or female patients 0 to 3. Patients 2 to 4. Female patients who have had menarche must test negative for pregnancy, as per local practice, at screening and check-in 5. Female patients who have had menarche and are sexually active must agree to use an effective contraception method, per local practice, for at least 30 days prior to edoxaban dose 6. Patients/Legal guardian(s) must agree to food and drug restrictions during the study 7. Patients must agree to abstain from the use of nonsteroidal anti-inflammatory drugs (such as ibuprofen), and antiplatelet and anticoagulant agents (except for low-dose aspirin) from 24 hours prior to edoxaban dose until after the last PK sample is collected 8. Patients on low-dose aspirin treatment (1 to 5 mg/kg/day, maximum of 100 mg/day) with an interruption of aspirin 24 hours prior to edoxaban dose and resuming 24 hours after edoxaban dose are permitted to participate in the study per the Investigatorâ??s judgment that this does not place the patients at risk 9. Patients must agree to abstain from CYP3A4 inhibitors/inducers and P-gp inhibitors/inducers for 14 days prior to the edoxaban dose to until after the last PK sample is collected 10. Patients must agree to abstain from and/or legal guardians must agree not to give the patient cola, tea, coffee, chocolate, and other caffeinated drinks and food from 48 hours before dose administration through the end of the study 11. Other than signs and symptoms characteristic to their disease state, patients are to be in good health as determined by the absence of clinically significant deviations from normal, with respect to medical and surgical history, physical examination, vital signs, and laboratory reports, as deemed by the Investigator and the Sponsor, prior to enrollment 12. Patients must agree to abstain from and/or legal guardians must agree not to give the p
Exclusion criteria
Exclusion criteria: 1. History (within the last 6 months) of abnormal coagulation tests during screening, as defined by local laboratory reference ranges, which are not explained by anticoagulation therapy or temporary concomitant affections 2. Stroke where anticoagulant therapy is contraindicated 3. Patients with stage 2 hypertension defined as blood pressure confirmed > 99th percentile + 5 mmHg 4. Patients with renal function less than 50% of normal for age and size as determined by the National Kidney Disease Education Program version of the Schwartz formula 5. Actively bleeding or has a high risk of bleeding 5. Actively bleeding or has a high risk of bleeding 6. Has a currently active gastrointestinal ulceration or a known history of peptic ulcer or gastrointestinal bleeding (including hematemesis, melena, or rectal bleeding including bleeding from hemorrhoids) within the previous 6 months 7. Has known diabetic retinopathy 8. Has thrombocytopenia at screening ( 9. Has had other unrelated clinically significant illness within 4 weeks prior to Day 1, predose 10. Planned invasive procedures during or within 24 hours of study drug administration 11. Patient is receiving high-dose aspirin concurrently or within 2 weeks prior to dosing 12. Use of P-gp or CYP 3A4 inhibitors or inducers within 14 days prior to the edoxaban dose and expected to continue through the study duration 13. Patients with history of major bleeding and/or neurosurgery within 6 months of dosing 14. Patients with history of major trauma or surgery within the last month 15. Patients with known malabsorption disorders (e.g., cystic fibrosis or short bowel syndrome)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetic parameters such as apparent systemic clearance (CL/F), apparent volume of distribution (V/F), and area under the concentration-time curve (AUC) for edoxaban and metabolites, and metabolite/parent ratios for AUCTimepoint: within 36 hours post dose | — |
Secondary
| Measure | Time frame |
|---|---|
| Observed, change-from-baseline, and percent-change-from-baseline PT, aPTT, and anti-FXa.Timepoint: within 36 hours post dose;Other: Palatability of the liquid formulation will be assessed using visual analog scale (VAS) scoresTimepoint: within 30 minutes of dosing;Safety: Safety assessments: adverse events, physical examination findings, vital signs, clinical laboratory assessments, and urinalysis.Timepoint: Predose to Day 10 | — |
Countries
Australia, Austria, Canada, Egypt, Finland, France, Germany, India, Iran (Islamic Republic of), Ireland, Israel, Italy, Jordan, Lebanon, Russian Federation, Spain, Switzerland, Turkey, United Kingdom, United States of America
Contacts
Public ContactDr Preeti Kabra
Medpace Clinical Research India Pvt. Ltd.
Outcome results
None listed