venous thromboembolism MedDRA version: 21.1 Level: LLT Classification code 10066899 Term: Venous thromboembolism System Organ Class: 100000004866
Conditions
Interventions
Trade Name: Lixiana 15 mg film-coated tablets
Product Code: DU176B
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: EDOXABAN (as anhydrous free form)
CAS Number: 480449-71-6
Other descript
Sponsors
Daiichi Sankyo, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 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. 5. Subjects with hepatic disease associated with coagulopathy leading to a clinically relevant bleeding risk (aPTT> 50 seconds or international normalized ratio [INR] > 2.0 not related to anticoagulation therapy) or ALT >5 x the upper limit of normal (ULN) or total bilirubin > 2x ULN with direct bilirubin > 20% of the total at Screening Visit. 6. Subjects with glomerular filtration rate (GFR) 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 any condition that, as judged by the Investigator, would place the subject at increased risk of harm if he/she participated in the study ncluding contraindicated medications identified in Appendix 17.4. 12. Subjects who participated in another clinical study or were treated with an experimental therapy with less than 30-day washout period prior to identifying the qualifying index VTE.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to demonstrate the non-inferiority of edoxaban to standard of care (SOC; including low molecular weight heparin (LMWH), vitamin K antagonist (VKA), or synthetic pentasaccharide (SP) Xa inhibitors) in the treatment and secondary prevention of VTE in pediatric subjects with regard to the composite efficacy endpoint (ie, symptomatic recurrent VTE, death as result of VTE, and no change or extension of thrombotic burden) during the first 3-month treatment period(for Cohort 5, the intended duration of treatment is 6-12 weeks). ;Secondary Objective: -To compare edoxaban vs SOC:during the first 3-month treatment period(for Cohort 5, the intended duration of treatment is 6-12 weeks)as regards: •a combination of major and CRNM bleedings occurring during or within 3 days of completing, interrupting or stopping treatment •the individual components of the composite efficacy endpoints from first to the last dose +30 days regarding: •the occurrence of DVT, catheter-related thrombosis,PE,sinovenous thrombosis •a combination of major and CRNM bleedings, symptomatic recurrent VTE, and death due to VTE •all bleedings •a composite combination of major and CRNM bleedings from randomization to the last dose +30 days regarding: •the composite efficacy endpoint/all-cause mortality To characterize the multiple dose PK of edoxaban and to assess the effect of certain covariates on the edoxaban PK To evaluate the relationship between edoxaban exposure and safety and efficacy To characterize the effect of edoxaban on biomarkers of coagulation;Primary end point(s): The primary efficacy endpoint is the composite endpoint consisting of incidence of symptomatic recurrent venous thromboembolic disease, death as result of VTE, and no change or extension of thrombotic burden (as defined in the protocol) during the first 3-months period. -For subjects in Cohort 5, (ie, <6 months old), the primary efficacy endpoint is a composite endpoint consisting of the incide | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints include: A composite endpoint consisting of the incidence of symptomatic recurrent venous thromboembolic disease, death as a result of VTE, and no change or extension of thrombotic burden from randomization to the date of the last dose of study drug + 30 days. The individual components of the primary efficacy endpoint during the first 3 month period (for Cohort 5, the intended duration of treatment is 6-12 weeks):: ? Symptomatic recurrent VTE ? Death as a result of VTE ? No change or extension of thrombotic burden. All-cause mortality from randomization to last dose + 30 days. The DVT, Catheter-related thrombosis, PE, and sinovenous thrombosis events within and after the first 3-month treatment period(for Cohort 5, the intended duration of treatment is 6-12 weeks).. Net Clinical Outcome Endpoint: Composite of symptomatic recurrent VTE events, death as a result of VTE, and major and CRNM bleeding that occurred from the date of the first dose of study drug to the date of last dose of study drug + 30 days. Safety Endpoints: The safety endpoints are: A combination of major and clinically relevant non- major (CRNM) bleedings occurring during treatment or within 3 days of completing or interrupting or stopping study during the first 3- month treatment period. For subjects in Cohort 5, ie,<6 months old, the primary safety endpoint, is a combination of major and CRNM bleedings occurring during treatment or within 3 days of completing or interrupting or stopping study within 6 to 12 weeks period + 3 days. All bleedings from first to the last dose + 30 days. A combination of major and CRNM bleedings from first to the last dose + 30 days. Pharmacokinetic and Pharmacodynamic Endpoints: Approximately, the first 12 subjects of each cohort (total of approximately 53 to 60 subjects) randomized to the edoxaban treatment arm will participate in the multiple-dose PK/Pd assessment on Day 5. Pharmacokinetics: Using popula | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Croatia, Czechia, Czech Republic, Denmark, Egypt, France, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy, Kenya, Korea, Democratic People's Republic of, Lebanon, Malaysia, Mexico, Netherlands, New Zealand, Norway, Panama, Philippines, Poland, Portugal, Romania, Russian Federation, Serbia, Singapore, Slovakia, Slovenia, Spain, Sweden, Switzerland, Thailand, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Contact
Daiichi Sankyo , Inc.
Outcome results
None listed