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

NCT ID: NCT00725881

Last Updated: 2011-07-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-08-31

Study Completion Date

2010-03-31

Brief Summary

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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

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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.

Conditions

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Intermittent Claudication

Keywords

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PAD Peripheral arterial disease Peripheral artery disease Intermittent claudication IC atherosclerosis leg pain walking pain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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1

.25 mg/kg TSC

Group Type EXPERIMENTAL

Trans sodium crocetinate (TSC)

Intervention Type DRUG

Once-daily bolus intravenous injections in a superficial vein of the arm via syringe over a period of up to 2 minutes. Each patient will receive up to 5 doses given on 5 consecutive days

2

.5 mg/kg TSC

Group Type EXPERIMENTAL

Trans sodium crocetinate (TSC)

Intervention Type DRUG

Once-daily bolus intravenous injections in a superficial vein of the arm via syringe over a period of up to 2 minutes. Each patient will receive up to 5 doses given on 5 consecutive days

3

.75 mg/kg TSC

Group Type EXPERIMENTAL

Trans sodium crocetinate (TSC)

Intervention Type DRUG

Once-daily bolus intravenous injections in a superficial vein of the arm via syringe over a period of up to 2 minutes. Each patient will receive up to 5 doses given on 5 consecutive days

4

1.0 mg/kg TSC

Group Type EXPERIMENTAL

Trans sodium crocetinate (TSC)

Intervention Type DRUG

Once-daily bolus intravenous injections in a superficial vein of the arm via syringe over a period of up to 2 minutes. Each patient will receive up to 5 doses given on 5 consecutive days

5

1.25 mg/kg TSC

Group Type EXPERIMENTAL

Trans sodium crocetinate (TSC)

Intervention Type DRUG

Once-daily bolus intravenous injections in a superficial vein of the arm via syringe over a period of up to 2 minutes. Each patient will receive up to 5 doses given on 5 consecutive days

6

1.5 mg/kg TSC

Group Type EXPERIMENTAL

Trans sodium crocetinate (TSC)

Intervention Type DRUG

Once-daily bolus intravenous injections in a superficial vein of the arm via syringe over a period of up to 2 minutes. Each patient will receive up to 5 doses given on 5 consecutive days

7

1.75 mg/kg TSC

Group Type EXPERIMENTAL

Trans sodium crocetinate (TSC)

Intervention Type DRUG

Once-daily bolus intravenous injections in a superficial vein of the arm via syringe over a period of up to 2 minutes. Each patient will receive up to 5 doses given on 5 consecutive days

8

2.0 mg/kg TSC

Group Type EXPERIMENTAL

Trans sodium crocetinate (TSC)

Intervention Type DRUG

Once-daily bolus intravenous injections in a superficial vein of the arm via syringe over a period of up to 2 minutes. Each patient will receive up to 5 doses given on 5 consecutive days

9

5.0 mL 0.9% normal saline

Group Type PLACEBO_COMPARATOR

0.9% normal saline

Intervention Type DRUG

A total volume of 5.0 mL normal saline will be dosed in a superficial vein of the arm via syringe over a period of up to 2 minutes.

Interventions

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Trans sodium crocetinate (TSC)

Once-daily bolus intravenous injections in a superficial vein of the arm via syringe over a period of up to 2 minutes. Each patient will receive up to 5 doses given on 5 consecutive days

Intervention Type DRUG

0.9% normal saline

A total volume of 5.0 mL normal saline will be dosed in a superficial vein of the arm via syringe over a period of up to 2 minutes.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Diffusion Pharmaceuticals Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Diffusion Pharmaceuticals LLC

Locations

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Cardiology, P.C.

Birmingham, Alabama, United States

Site Status

Radiant Research, Inc.

Santa Rosa, California, United States

Site Status

Stanford University School of Medicine, Division of Cardiovascular Medicine

Stanford, California, United States

Site Status

Andrews Research and Education

Pensacola, Florida, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Clinical Trials of Texas, Inc.

San Antonio, Texas, United States

Site Status

Countries

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United States

References

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Mohler ER 3rd, Gainer JL, Whitten K, Eraso LH, Thanaporn PK, Bauer T. Evaluation of trans sodium crocetinate on safety and exercise performance in patients with peripheral artery disease and intermittent claudication. Vasc Med. 2011 Oct;16(5):346-53. doi: 10.1177/1358863X11422742.

Reference Type DERIVED
PMID: 22003000 (View on PubMed)

Other Identifiers

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DP100-301

Identifier Type: -

Identifier Source: org_study_id