A Randomized, Double-Blinded, Placebo-Controlled Phase 1/2 Dose-Range-Finding Study to Evaluate the Safety, Efficacy and PK of Multiple Once Daily Intravenous Doses of TSC in Patients With Intermittent Claudication

Diffusion Pharmaceuticals Inc7 sites in 1 country48 target enrollmentAugust 2008

ConditionsIntermittent Claudication

InterventionsTrans sodium crocetinate (TSC)0.9% normal saline

DrugsTrans sodium crocetinate (TSC)0.9% normal saline

Overview

Phase: Phase 1
Intervention: Trans sodium crocetinate (TSC)
Conditions: Intermittent Claudication
Sponsor: Diffusion Pharmaceuticals Inc
Enrollment: 48
Locations: 7
Primary Endpoint: Safety (laboratory tests, vital signs, ECG, physical exam, pulse oximetry) and pharmacokinetic assessments
Status: Completed
Last Updated: 14 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief 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.

Detailed Description

Peripheral Artery Disease (PAD) is a manifestation of systemic atherosclerosis, and patients with PAD commonly manifest symptoms of intermittent claudication (IC) such as cramping, aching, or fatigue in the calf muscles provoked by activity. In PAD, arterial occlusions lead to decreased leg blood flow during exercise or walking and the pain associated with this ischemia is IC. The diffusion of oxygen from blood to muscle could be a component of the overall decreased delivery or deficit of oxygen (hypoxia) to skeletal muscle resulting in symptoms in PAD patients. The overall goal of the development of TSC as a treatment for PAD is to allow for enhanced diffusion of oxygen through the plasma to alleviate the symptoms caused by the hypoxia in the tissues. This double-blinded, placebo-controlled clinical trial will randomize up to 48 patients at up to 8 clinical research sites in the US. In addition to safety and pharmacokinetic assessments conducted during the trial, the primary endpoint of the study will be demonstrated from standardized, graded exercise treadmill tests conducted throughout the study. The clearly measurable parameters will be peak walking time (PWT) and claudication onset time (COT) comparing baseline and after TSC or placebo and are well-established endpoints accepted by the medical community and regulatory authorities for IC clinical trials.

Registry

clinicaltrials.gov

Start Date

August 2008

End Date

March 2010

Last Updated

14 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Diffusion Pharmaceuticals Inc

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

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