Edoxaban in Peripheral Arterial Disease

Inclusion Criteria:

- Male or female subjects older than the minimum legal adult age (country specific);

- Rutherford stages 2-5 provided there are no ulcerations on the heel and/or exposed
tendon and/or bone;

- Superficial femoral above knee-popliteal ( 3 cm proximal to the medial femoral
condyle) lesion and ≥ 50% stenosis or occlusion;

- At least one run-off vessel to the foot with or without additional endovascular
intervention;

- Successful intervention, defined as angiographic confirmation of ≤ 30% residual
stenosis and absence of flow limiting dissection;

- Adequate hemostasis at the vascular access site within 24 hours of intervention;

- A subject is also eligible if they have undergone additional successful endovascular
intervention(s) during the index intervention;

- Able to provide signed informed consent.

Exclusion Criteria:

- Calculated Creatinine Clearance < 30 ml/min;

- Femoral or popliteal aneurysm;

- Adjunctive use of thrombolytics;

- Any extravasation or distal embolization not successfully treated;

- Uncontrolled hypertension as judged by the investigator (e.g., systolic blood pressure
> 170 mmHg or diastolic blood pressure > 100 mmHg despite antihypertensives);

- Aspirin intolerance;

- Clopidogrel intolerance;

- Contraindication for anticoagulants or antiplatelets and any other contraindication
listed in the local labeling of aspirin and/or clopidogrel;

- 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;

- 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;

- Treatment with cilostazol within 24 hours of randomization;

- 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];

- Prior stroke or myocardial infarction (MI) or acute coronary syndrome within 3 months;

- 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;

- Prior history of a positive test for Hepatitis B antigen or Hepatitis C antibody;

- 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;

- Subjects previously randomized to an edoxaban (DU-176b) study;

- 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;

- 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;

- 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);

- Subjects with any condition that, in the opinion of the Investigator, would place the
subject at increased risk of harm if he/she participated in the study;

- History of heparin-induced thrombocytopenia