A Phase 3, Open-Label, Study to Evaluate Pharmacokinetics and Pharmacodynamics of Edoxaban and to compare the safety and efficacy of Edoxaban with standard of care treatment in Paediatric Patients confirmed as requiring treatment for a blood clot
- Conditions
- venous thromboembolismMedDRA version: 21.1Level: LLTClassification code 10066899Term: Venous thromboembolismSystem Organ Class: 100000004866Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2016-000991-49-CZ
- Lead Sponsor
- Daiichi Sankyo, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 274
Subjects must satisfy all of the following criteria to be included in the study:
1. Male or female pediatric subjects between birth (defined as 38 weeks gestational age) and less than 18 years of age at the time of consent.
2. Pediatric subjects with the presence of documented VTE confirmed by
appropriate diagnostic imaging and requiring anticoagulant therapy for
at least 90 days.
-Subjects <6 months old (Cohort 5) with the presence of documented
VTE confirmed by appropriate diagnostic imaging and requiring
anticoagulant therapy for at least 6 to12 weeks
3. Subjects must have received at least 5 days of heparin (LMWH or SP Xa inhibitors or UFH according to the edoxaban label for VTE treatment) therapy prior to randomization to treat the newly identified index VTE. In addition, prior to being randomized to edoxaban or SOC, subjects initially treated with VKA are
recommended to have an INR = 2.5.
4. Subject and/or parent(s)/legal guardian(s) or legally acceptable representative is informed and provides signed consent for the child to participate in the study with edoxaban treatment. Pediatric subjects with appropriate intellectual maturity will be required to sign an assent form in addition to the signed informed consent from the parent(s)/legal guardian(s) or any legally acceptable representative.
5. Female subjects who have menarche must test negative for pregnancy at Screening and must consent to avoid becoming pregnant by using an approved contraception method throughout the study.
The following use of reliable method(s) of contraception, and/or abstinence, for the duration of therapeutic product exposure is recommended.
a. Highly effective methods:
Highly effective methods of contraception, when used consistently and correctly, result in low failure rates. These may include: intrauterine device (IUD) or intrauterine system (IUS); vasectomy and tubal ligation. Highly effective methods of contraception might not always be achievable in the clinical trial setting and, therefore, the most effective alternative can be achieved using methods in combination.
b. Effective methods:
Effective methods may include: barrier methods of contraception (eg, male condom, female condom, cervical cap, diaphragm, contraceptive sponge).
Note: When used consistently and correctly, double barrier methods of contraception (eg, male condom with diaphragm, male condom with cervical cap) can be used as an effective alternative to the highly effective contraception methods described above.
Are the trial subjects under 18? yes
Number of subjects for this age range: 274
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
Subjects who meet any of the following criteria will be disqualified from entering the
study:
1. Subjects with active bleeding or high risk of bleeding contraindicating treatment with LMWH, SP Xa inhibitors, VKAs, or direct oral anticoagulants (DOACs; identified high risk of bleeding during prior experimental administration of DOACs).
2. Subjects who have been or are being treated with thrombolytic agents, thrombectomy or insertion of a caval filter for the newly identified index VTE.
3. Administration of antiplatelet therapy is contraindicated in both arms except for low dose aspirin defined as 1-5 mg/Kg/day with maximum of 100 mg/day.
4. Administration of rifampin is prohibited during the study and subjects
on concomitant use of rifampin are excluded.
5a. Subjects with severe hepatic impairment or hepatic disease
associated with coagulopathy (eg acute hepatitis, chronic active
hepatitis, and cirrhosis).
b) Subjects with ALT > 5 × the upper limit of normal (ULN) or total
bilirubin >2 × ULN with direct bilirubin > 20% of the total at Screening.
c) Subjects with aPTT >50 seconds or international
normalized ratio [INR] >2.0 not related to
anticoagulation therapy.
6. Subjects with estimated glomerular filtration rate (GFR) < 30% of
normal for age and size
7. Subjects with stage 2 hypertension defined as blood pressure (BP)
systolic and/or diastolic confirmed > 99th percentile + 5 mmHg.
8. Subject with thrombocytopenia <50 × 109/L at Screening Visit.
Subjects with a history of heparin-induced thrombocytopenia may be
enrolled in the study at the Investigator's discretion.
9. Life expectancy less than the expected study treatment duration (3
months).
10. Subjects who are known to be pregnant or breastfeeding.
11. Subjects with the following diagnosis and situations: active cancer undergoing chemotherapy, radiation, or major surgery within the next 3 months.
12. Subjects who participated in another interventional clinical study or
were treated with an experimental therapy with less than a 30-day
wash-out period prior to identifying the qualifying index VTE.
13. Hypersensitivity to the active ingredient or to any of the excipients of
any components of the trial treatment.
14. Patients with a history of thrombosis who are diagnosed with
antiphospholipid syndrome who are triple positive (for lupus
anticoagulant, anticardiolipin antibodies, and anti-beta 2-glycoprotein I
antibodies).
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