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

• Status: Completed
• Trial end date: 2010-03-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to evaluate the safety and pharmacokinetics of multiple, once-daily, intravenous doses of trans sodium crocetinate (TSC). The effectiveness of TSC in alleviating the symptoms of intermittent claudication (IC) will also be assessed.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Diffusion Pharmaceuticals Inc; Diffusion Pharmaceuticals LLC
• Treatments: Trans-sodium crocetinate; Vitamin A

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