A study of an oral anticoagulant (Edoxaban) in childre

Phase 1

Conditions: Patients who are at risk of thromboembolic events (e.g., patients with thrombophilia, congenital heart disease, presence of a central venous catheter)
Patients with cardiac conditions who may need anticoagulation therapy
or Patients with sickle cell disease who may need anticoagulation therapy.
MedDRA version: 19.0 Level: LLT Classification code 10010495 Term: Congenital heart disease NOS System Organ Class: 100000004850
MedDRA version: 19.0 Level: LLT Classification code 10057396 Term: Thrombophilia System Organ Class: 100000004851
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Registration Number: EUCTR2015-005732-18-FR

Lead Sponsor: Daiichi Sankyo , Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: A

Sex: Not specified

Target Recruitment: 48

Inclusion Criteria

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 < 18 years of age on the day of dosing
3. Patients 2 to < 18 years of age must have a body mass index (BMI) between the 5th and 95th percentile based on the 2000 CDC Growth Charts7 (the maximum number of patients in each dose group that have a BMI between 85th and 95th percentile should not be more than 2 patients). Patients < 2 years of age must have a body weight between the 5th and 90th percentile based on the 2000 CDC Growth Charts7
4. Female patients who have had menarche must test negative for pregnancy at screening and check-in
5. Female patients who have had menarche and are sexually active must use an acceptable contraception method 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 Investigator’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 (See Section 5.2)
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 check-out (See Section 5.3 for a complete list)
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 patient St. John’s Wort and food/supplement and beverages containing grapefruit, grapefruit juice, and Seville oranges from 14 days before the first dose through the end of the study (See Section 5.3)
Are the trial subjects under 18? yes
Number of subjects for this age range: 48
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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
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 formula8
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 (< 20 × 109/L)
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)
16. Hepatic disease which is associated with coagulopathy leading to a clinically relevant bleeding risk or 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
17. Patient is currently enrolled in another investigational device or drug study, or is receiving other investigational agents. Patients must have completed the prior clinical study at least 30 days prior to dosing
18. Patients of childbearing potential (post-menarche) who are sexually active and are not using approved contraception; who are pregnant (as based on test results); or are breastfeeding
19. Females with history of abnormal menses, including history of menorrhagia (heavy menstrual bleeding), metrorrhagia, or polymenorrhea
20. Patient has known sensitivity to the investigational product (IP) or any of its excipients
21. Positive drug or alcohol screen (excluding cotinine) at screening for patients 12 years of age or older, for newborns and for patients who are being breastfed
22. Patients who have received a transfusion or any blood products within 30 days prior to the first dose
23. Any major bleeding during prior anticoagulant therapy
24. Patients with any condition, that as judged by the Investigator, would place the patient at increased risk of harm if he/she participated in the study

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

Related Trials