Clinical trial NCT00725881 (phase 1/phase 2, status: completed)
Conditions: intermittent claudication
ICD codes: I70.211, I70.212, I70.213, I70.218, I70.219, I70.611, I70.612
Drugs: trans sodium crocetinate (tsc), 0.9% normal saline
SMILES: C\C(\C=C\C=C(/C)C(O)=O)=C/C=C/C=C(\C)/C=C/C=C(\C)C(O)=O, [Na+].[Cl-]
Eligibility criteria:

        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