Edoxaban is being investigated for use in PAD subjects after femoropopliteal endovascular interventions with/without stent placement for the maintenance of patency and prevention of re-intervention. MedDRA version: 17.0 Level: LLT Classification code 10067825 Term: Peripheral arterial disease System Organ Class: 100000004866
Conditions
Interventions
Product Name: Edoxaban tosylate
Product Code: DU-176b
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Edoxaban
CAS Number: 480449-70-5
Current Sponsor code: DU-176b
Other descriptive name
Sponsors
Daiichi Sankyo Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects older than the minimum legal adult age (country specific); 2. Rutherford stages 2-5 provided there are no ulcerations on the heel and/or exposed tendon and/or bone; 3. Superficial femoral, above-knee popliteal (3 cm proximal to the medial femoral condyle) lesion and = 50% stenosis or occlusion; 4. At least one run-off vessel to the foot with or without additional endovascular intervention; 5. Successful intervention, defined as angiographic confirmation of = 30% residual stenosis and absence of flow limiting dissection; 6. Adequate hemostasis at the vascular access site within 24 hours of intervention; 7. A subject is eligible if they have undergone additional successful endovascular intervention(s) during the index intervention; 8. Able to provide signed informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 80 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 120
Exclusion criteria
Exclusion criteria: 1. Calculated CrCL 170 mmHg or diastolic blood pressure > 100 mmHg despite antihypertensives); 6. Aspirin intolerance; 7. Clopidogrel intolerance; 8. Contraindication for anticoagulants or antiplatelets and any other contraindication listed in the local labeling of aspirin and/or clopidogrel (see Appendix 17.8 for US and EU labeling); 9. Active bleeding or known high risk for bleeding or history of intracranial, or spontaneous intraocular, spinal retroperitoneal or intra-articular bleeding; overt gastrointestinal (GI) bleeding or active ulcer within the previous year; 10. Subjects receiving dual antiplatelet or anticoagulant therapy at the time of randomization; subjects receiving pre-interventional loading dose of clopidogrel or other P2Y12 receptor antagonists; see Appendix 17.5. for details; 11. Treatment with cilostazol within 24 hours of randomization; 12. Subjects receiving prohibited concomitant medications [fibrinolytics, chronic use of non steroidal anti-inflammatory drugs (NSAIDS) > 4 days per week, and oral or parenteral non-aspirin NSAIDs and strong P-gp inhibitors]; see Appendix 17.5 for list of prohibited concomitant medications; 13. Prior stroke or MI or acute coronary syndrome within 3 months; 14. Chronic liver disease [alanine transaminase (ALT) and/or aspartate transaminase (AST) = 2 × upper limit of normal; total bilirubin (TBL) = 1.5 × upper limit of normal]; however, subjects whose elevated TBL is due to known Gilbert's syndrome may be included in the study; 15. Prior history of a positive test for Hepatitis B antigen or Hepatitis C antibody; 16. Subjects who received any investigational drug or device within 30 days prior to randomization, or plan to receive such investigational therapy during the study period; 17. Subjects previously randomized to an edoxaban (DU-176b) study; 18. Women of childbearing potential without proper contraceptive measures (i.e. a method of contraception with a failure rate < 1 % during the course of the study including the observational period) and women who are pregnant or breast feeding; Note: These methods of contraception according to the note for guidance on nonclinical safety studies for the conduct of human trials for pharmaceuticals (CPMP/ICH/286/95, modification) include consistent and correct use of hormone containing implants and injectables, combined oral contraceptives, hormone containing intrauterine devices, surgical sterilization, sexual abstinence, and vasectomy for the male partner; 19. Subjects with the following diagnoses or situations: - Active malignancy except for adequately treated non-melanoma skin cancer or other non-invasive or in-situ neoplasm (e.g., cervical cancer in situ); - Concurrent treatment with cancer therapy (drugs, radiation, and/or surgery); - Other significant active concurrent medical illness or infection; - Life expectancy < 12 months; 20. Subjects who are unlikely to comply with the protocol (e.g., uncooperative attitude, inability to return for subsequent visits, and/or otherwise considered by the Investigator to be unlikely to complete the study); 21. Subjects with any condition that, in the opinion of the Investigator, would place the subject at increased risk of harm i
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate clinically relevant bleeding (i.e., major or clinically relevant nonmajor bleeding) occurring during treatment or within 3 days of interrupting or stopping study drug. - To evaluate re-stenosis/re-occlusion [defined as peak systolic velocity (PSV) ratio >/= 2.4] at the treated segment(s) measured at 1, 3 and 6 months after randomization using color coded duplex ultrasonography scanning (DUS).;Secondary Objective: -To evaluate any bleeding (major, clinically relevant non-major, and minor bleeding) occurring during treatment or within 3 days of interrupting or stopping study drug. - To evaluate all other clinical and laboratory safety assessments including adverse events (AEs), serious adverse events (SAEs), and other events of special interest (i.e., hepatic events). - To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of edoxaban in PAD subjects.;Primary end point(s): Primary Safety Endpoint: The primary safety endpoint is clinically relevant bleeding (i.e., major or clinically relevant non major bleeding) occurring during treatment or within 3 days of interrupting or stopping study drug. Primary Efficacy Endpoint: The primary efficacy endpoint is re-stenosis/reocclusion (as defined by PSV ratio >= 2.4) at the treated segment(s) measured at 1, 3 and 6 months, using color-coded DUS.;Timepoint(s) of evaluation of this end point: Primary Safety Endpoint: During treatment or within 3 days of interrupting or stopping study drug. Primary Efficacy Endpoint: measured at 1, 3 and 6 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): · Change in PSV ratio in the treated segment(s) at 3 and 6 months compared to 1 month; · Change from baseline ABI at 3 and 6 months; · Rutherford stage at 1, 3 and 6 months; · Symptomatic acute thrombosis; · Target lesion revascularization (percutaneous or surgical); · MACE; · SEE (fatal and non-fatal) · All cause mortality; · Amputations; · PK: Plasma concentrations of edoxaban and its metabolite (D21-2393) on Days 30 and 90; · Pharmacodynamics (PD): Plasma concentrations of PD biomarkers on Days 30 and 90 (anti-FXa activity, intrinsic FX, aPTT, PT/INR, D-dimer, sP-selectin, CRP and TGA).;Timepoint(s) of evaluation of this end point: PSV ratio - 3 and 6 months and 1 month - used as comparison Change from baseline ABI - 1, 3 and 6 months Rutherford stage - screening, 1, 3 and 6 months PK – Days 30 and 90 PD – Days 30 and 90 All other secondary endpoints – throughout the study | — |
Countries
Austria, Belgium, Germany, Israel, Netherlands, Switzerland, United States
Contacts
Public ContactClinical Trial Information
Daiichi Sankyo Development Ltd
Outcome results
None listed