- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00725881
Safety, Efficacy, and Pharmacokinetics (PK) Study of Trans Sodium Crocetinate (TSC) in Patients With Intermittent Claudication
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
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Alabama
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Birmingham, Alabama, United States, 35211
- Cardiology, P.C.
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California
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Santa Rosa, California, United States, 95405
- Radiant Research, Inc.
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Stanford, California, United States, 94305-5406
- Stanford University School of Medicine, Division of Cardiovascular Medicine
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Florida
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Pensacola, Florida, United States, 32561
- Andrews Research and Education
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Oklahoma
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Oklahoma City, Oklahoma, United States, 73104
- University of Oklahoma Health Sciences Center
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- Hospital of the University of Pennsylvania
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Texas
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San Antonio, Texas, United States, 78229
- Clinical Trials of Texas, Inc.
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: 1
.25 mg/kg 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
|
EXPERIMENTAL: 2
.5 mg/kg 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
|
EXPERIMENTAL: 3
.75 mg/kg 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
|
EXPERIMENTAL: 4
1.0 mg/kg 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
|
EXPERIMENTAL: 5
1.25 mg/kg 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
|
EXPERIMENTAL: 6
1.5 mg/kg 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
|
EXPERIMENTAL: 7
1.75 mg/kg 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
|
EXPERIMENTAL: 8
2.0 mg/kg 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
|
PLACEBO_COMPARATOR: 9
5.0 mL 0.9% normal saline
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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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
Screening, Baseline, Dose 1, Dose 2, Dose 3, Dose 4, Dose 5, 5-Day Follow-up, 14-Day Follow-up
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
Baseline, Dose 1, Dose 5, 5-Day Follow-up
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- DP100-301
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Intermittent Claudication
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Mid and South Essex NHS Foundation TrustRecruitingPeripheral Arterial Disease | Claudication, IntermittentUnited Kingdom
-
Louis MessinaBioMarin PharmaceuticalRecruitingPeripheral Vascular Diseases | Peripheral Artery Disease | Claudication, IntermittentUnited States
-
University Hospital, AngersCompletedPeripheral Artery Disease | Claudication, IntermittentFrance
-
Palo Alto Veterans Institute for ResearchSociety for Vascular SurgeryWithdrawnPeripheral Artery Disease | Claudication, Intermittent
-
Biotronik AGCompletedSevere Intermittent Claudication | Patients With Symptomatic Critical Limb IschemiaGermany
-
University Hospital, EssenStraub Medical AGUnknownPeripheral Arterial Disease | Claudication, IntermittentGermany
-
University Hospital, EssenUnknownPeripheral Arterial Disease | Claudication, IntermittentGermany
-
Sheffield Teaching Hospitals NHS Foundation TrustUniversity Hospital, Angers; Imperial College London; Sheffield Hallam UniversityCompletedIntermittent ClaudicationUnited Kingdom
-
Paradigm SpineCompletedIntermittent Neurogenic Claudication (INC) as a Result of Spinal StenosisNetherlands
-
Imperial College LondonTerminatedStandardised Claudication Treadmill TestUnited Kingdom
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