Table 1 Inclusion and exclusion criteria
Inclusion criteria | Subject is willing to comply with requirements of the study protocol |
Male and female patients ≥ 18 years of age | |
Type 2 diabetes mellitus | |
Symptomatic or known PAD/claudication | |
Symptomatic PAD or Ankle-brachial index ≤ 0.85 or calcified blood vessels with toe-brachial index ≤ 0.6 and/or abnormal post-exercise ankle–brachial index or prior surgical or percutaneous intervention of the peripheral arteries ≥ 12 months previously with a residual stenoses of ≥ 50% in a non-dilated artery | |
Exclusion criteria | Type I diabetes, poorly controlled diabetes (HbA1c < 8.5%). Newly diagnosed type 2 diabetes (within 6 months of randomization) or laboratory evidence of diabetes during screening (fasting serum glucose ≥ 126 mg/dL [7.0 mmol/L] or HbA1c ≥ 6.5%) without prior diagnosis of diabetes |
Uncontrolled hypertension defined as sitting systolic blood pressure (SBP) > 180 mmHg or diastolic BP (DBP) > 100 mmHg | |
NYHA III or IV heart failure, or last known left ventricular ejection fraction (LVEF < 30%) | |
Female subject who has either (1) not used at least 1 highly effective method of contraception for at least 1 month prior to screening or (2) is not willing to use such a method during treatment and for an additional 15 weeks after the end of treatment unless the subject is sterilized or postmenopausal. Menopause is defined as: 12 months of spontaneous and continuous amenorrhea in a female ≥ 55 years old or 12 months of spontaneous and continuous amenorrhea with follicle-stimulating hormone (FSH) level > 40 iU/L (according to the definition of “postmenopausal range” for the laboratory involved) in a female < 55 years old unless the subject has undergone bilateral oophorectomy. Highly effective methods of birth control include: not having intercourse or using birth control methods that work at least 99% of the time when used correctly and include: birth control pills, shots, implants, or patches, intrauterine devices (IUDs), tubal ligation/occlusion, sexual activity with a male partner who has had a vasectomy, condom or occlusive cap (diaphragm or cervical/vault caps) used with spermicide | |
Subject is pregnant or breast-feeding, or planned to become pregnant during treatment and/or within 15 weeks after the end of treatment | |
History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outline above) that in the opinion of the Investigator or Sponsor, if consulted, would pose risk to subject safety or interferes with the study evaluation, procedures or completion (e.g. active malignancy other than squamous cell or basal cell skin cancer, use of strong or moderate CYP2C19 inhibitors, long-term concomitant treatment with non-steroidal anti-inflammatory drugs [NSAIDs]) | |
Unreliability as a study participant based on Investigator’s (or designee’s) knowledge of the subject (e.g. alcohol or other drug abuse, inability or unwillingness to adhere to the protocol, or psychosis) | |
Patients requiring dual anti-platelet therapy at study entry | |
Need for chronic oral anticoagulant therapy or chronic low-molecular-weight heparin or long-term treatment with fondaparinux | |
Planned revascularization (surgical or endovascular) in any vascular territory during the duration of the study | |
Planned major amputation due to PAD within the next 3 months or major amputation due to PAD within the last 30 days | |
Patients who have suffered a stroke during the past 3 months | |
Dementia likely to jeopardize understanding of information pertinent to study conduct or compliance to study procedures | |
Known bleeding diathesis, haemostatic or coagulation disorder, or systemic bleeding, whether resolved or ongoing | |
History of intracranial hemorrhage, gastrointestinal bleeding within the past 6 months, or major surgery with the past 3 months of screening (if surgical wound is judged to be associated with increased risk of bleeding and considered at risk for hemorrhagic events | |
Hypersensitivity or allergic reactions to aspirin, ticagrelor, or any other products or components administered during dosing or procedures | |
Concomitant use of anticoagulants such as warfarin, dabigatran, factor Xa inhibitors or antiplatelet drugs such as clopidogrel, dipyridamole and sulfapyridine | |
Subject has a condition or circumstance which would prevent them from adhering to treatment regimens | |
Subject has active infection (e.g. bacterial, fungal) within the previous 6 weeks prior to screening (Note: subjects with viral infection such as common cold are not excluded) | |
Subject has an anemia (hemoglobin ≤ 8.5 g/dL) that requires a potential blood transfusion within 6 weeks of screening | |
Subject has given blood or received a blood transfusion within the previous 3 months prior to screening | |
Subject has polycythemia vera or any hyperviscosity syndrome | |
Subjects with Waldenstrom’s macroglobulinemia who have an increased risk of hyperviscosity syndrome | |
Subjects with known severe liver disease (e.g., ascites and/or clinical signs of coagulopathy) or obstructive liver disease [(e.g. primary biliary cirrhosis or end-stage renal disease (eGFR ≤ 30 mL/min/m2)] | |
Subject has history of end stage renal disease (eGFR < 30 mL/min/m2 or renal failure requiring dialysis) | |
Subject who is likely to not be available to complete all protocol-required study visits or procedures and/or to comply with all required study procedures (e.g. blood collection procedures to ensure subject safety to the best of the subject and investigator’s knowledge) | |
Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational agent(s) | |
Family members or employees of the investigator or study centers involved in the study |