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

Sponsor:	Diffusion Pharmaceuticals LLC
Information provided by:	Diffusion Pharmaceuticals LLC
ClinicalTrials.gov Identifier:	NCT00725881

Purpose

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.

Condition	Intervention	Phase
Intermittent Claudication	Drug: Trans sodium crocetinate (TSC) Drug: 0.9% normal saline	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety Study
Official Title:	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

Further study details as provided by Diffusion Pharmaceuticals LLC:

Primary Outcome Measures:

Safety (laboratory tests, vital signs, ECG, physical exam, pulse oximetry) and pharmacokinetic assessments [ Time Frame: Screening, Baseline, Dose 1, Dose 2, Dose 3, Dose 4, Dose 5, 5-Day Follow-up, 14-Day Follow-up ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change in peak walking time (PWT) and claudication onset time (COT) in an exercise treadmill test [ Time Frame: Baseline, Dose 1, Dose 5, 5-Day Follow-up ] [ Designated as safety issue: No ]

Enrollment:	48
Study Start Date:	August 2008
Estimated Study Completion Date:	April 2010
Estimated Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental .25 mg/kg TSC	Drug: 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
2: Experimental .5 mg/kg TSC	Drug: 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
3: Experimental .75 mg/kg TSC	Drug: 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
4: Experimental 1.0 mg/kg TSC	Drug: 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
5: Experimental 1.25 mg/kg TSC	Drug: 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
6: Experimental 1.5 mg/kg TSC	Drug: 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
7: Experimental 1.75 mg/kg TSC	Drug: 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
8: Experimental 2.0 mg/kg TSC	Drug: 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
9: Placebo Comparator 5.0 mL 0.9% normal saline	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.

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.

Eligibility

Ages Eligible for Study:	40 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00725881

Locations

United States, Alabama
Cardiology, P.C.
Birmingham, Alabama, United States, 35211
United States, California
Radiant Research, Inc.
Santa Rosa, California, United States, 95405
Stanford University School of Medicine, Division of Cardiovascular Medicine
Stanford, California, United States, 94305-5406
United States, Florida
Andrews Research and Education
Pensacola, Florida, United States, 32561
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Clinical Trials of Texas, Inc.
San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Diffusion Pharmaceuticals LLC

More Information

No publications provided

Responsible Party:	Diffusion Pharmaceuticals LLC ( Kim M. Whitten, PharmD, RAC )
Study ID Numbers:	DP100-301
Study First Received:	July 29, 2008
Last Updated:	March 3, 2010
ClinicalTrials.gov Identifier:	NCT00725881 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Diffusion Pharmaceuticals LLC:

PAD
Peripheral arterial disease
Peripheral artery disease
Intermittent claudication

IC
atherosclerosis
leg pain
walking pain

Additional relevant MeSH terms:

Arterial Occlusive Diseases
Signs and Symptoms
Vascular Diseases

Intermittent Claudication
Cardiovascular Diseases
Arteriosclerosis

ClinicalTrials.gov processed this record on March 11, 2010