Safety, Efficacy, and Pharmacokinetics (PK) Study of Trans Sodium Crocetinate (TSC) in Patients With Intermittent Claudication

This is an interventional treatment trial for Intermittent Claudication focused on measuring PAD, Peripheral arterial disease, Peripheral artery disease, Intermittent claudication, IC, atherosclerosis, leg pain, walking pain Read More

Inclusion Criteria:

• Aged 40 or older, male or female
• 6-mo. history of walking limitation or symptoms of intermittent claudication (IC) in at least 1 lower limb, severity of which has not changed in the past 3 mo. and diagnosed by principal investigator as clinically stable Fontaine Stage II peripheral artery disease (PAD)
• Diagnosis of PAD secondary to atherosclerosis
• If ankle-brachial index (ABI) is > 1.3 or cannot be measured in either leg, vascular etiology documented by toe-brachial index (TBI) ≤ 0.7 in at least 1 leg
• Claudication severity, meds. for the treatment of coronary artery disease (CAD), PAD and IC, and exercise habits should be clinically stable for 3 mo. prior to Screening (SCRN) and during study. Pt. is not likely to change smoking and/or exercise habits during study
• On an exercise treadmill test (ETT), peak walking time (PWT) of at least 1 min., but no more than 12 min. at Baseline
• Willing and able to discontinue Pletal or Trental for 21 days before SCRN and during study
• Antihypertensive therapy, cholesterol-lowering therapy, chronic oral nitrates, and diabetic therapy have been stable for 30 days prior to SCRN
• Willing and able to provide written, signed, informed consent after the nature of the study has been explained and prior to any research-related procedures
• Willing and able to comply with all study-related procedures
• Sexually active patients must use an acceptable method of contraception while participating in the study
• Females of childbearing potential must have a negative pregnancy test at SCRN and have additional pregnancy tests during the study

Exclusion Criteria:

• Pregnant or lactating
• Current or history of critical limb ischemia (CLI)
• Pts. in whom artery insufficiency in the lower extremity is the result of acute limb ischemia (ALI) or an immunological or inflammatory non-atherosclerotic disorder
• Pts. in whom walking impairment due to pain is the result of other non-atherosclerotic co-morbid conditions
• A surgical intervention to alleviate symptoms of IC or PAD-specific endovascular intervention or cardiovascular surgery within 3 mo. of SCRN
• Walking limited by reasons other than claudication
• Conditions other than IC of significant severity that could confound PWT on the ETT
• Concurrent severe congestive heart failure (CHF)
• Life-threatening ventricular arrhythmias, unstable angina, and/or myocardial infarction (MI) within 3 mo. before enrollment (ENRL)
• Coronary artery bypass grafting or percutaneous coronary intervention within 4 mo. before ENRL
• Renal and/or carotid revascularization procedure within 3 mo. of ENRL
• Transient ischemic attack (TIA) within 3 mo. before ENRL
• Deep vein thrombosis (DVT) within 3 mo. before ENRL
• Severe chronic obstructive pulmonary disease (COPD)
• Thrombocytopenia
• Undergoing hemodialysis or peritoneal dialysis
• Pts. w/immunocompromised conditions, organ transplant recipients and/or need for immunosuppressive therapy
• Neurological dementia
• Stroke
• Clinically significant electrocardiogram (ECG) change during or after ETT at SCRN or Baseline visit(s)
• Cerebrovascular infarct within 3 mo. of SCRN
• Poorly controlled type 1 or type 2 diabetes at SCRN
• History of migraine headaches within last 12 mo.
• Patients with clinically significant abnormal hematology labs or blood chemistry labs
• Body mass index > 35
• Hypertension at SCRN defined as resting BP values of > 170 mmHg systolic and/or > 110 mmHg diastolic
• Hypotension at SCRN defined as resting BP values < 100 mmHg systolic or < 55 mmHg diastolic or symptomatic hypotension
• Previous treatment with any formulation of TSC
• Known allergy or hypersensitivity to any excipient (gamma-cyclodextrin, mannitol, glycine) of TSC formulation
• Previous treatment with gene therapy or other VEGF-related treatment within 12 mo. of SCRN
• Patients with recent history of alcoholism or drug abuse, or severe emotional, behavioral, or psychiatric problems
• Patients receiving experimental medications or participating in other study using an experimental drug or procedure within 45 days prior to ENRL