Intermittent ClaudicationPhase 1/2NCT00725881
Safety, Efficacy, and Pharmacokinetics (PK) Study of Trans Sodium Crocetinate (TSC) in Patients With Intermittent Claudication
A Phase 1/2 study testing Trans sodium crocetinate (TSC) and 0.9% normal saline in people with Intermittent Claudication, run by Diffusion Pharmaceuticals Inc at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Intermittent Claudication
- What is being tested?
- Trans sodium crocetinate (TSC) and 0.9% normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 7 sitesUnited States
- Study dates
- Aug 2008to Mar 2010
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Cardiology, P.C.
Birmingham, Alabama, 35211
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Andrews Research and Education
Pensacola, Florida, 32561
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Clinical Trials of Texas, Inc.
San Antonio, Texas, 78229
Radiant Research, Inc.
Santa Rosa, California, 95405
Stanford University School of Medicine, Division of Cardiovascular Medicine
Stanford, California, 94305-5406
About this 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
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.
Read the 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.
- Conditions
- Intermittent Claudication
- Being tested
- Trans sodium crocetinate (TSC), 0.9% normal saline
- Keywords
- PAD, Peripheral arterial disease, Peripheral artery disease, Intermittent claudication, IC, atherosclerosis, leg pain, walking pain
- Medical subject headings
- Intermittent Claudication, Peripheral Arterial Disease, Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trans sodium crocetinate (TSC)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
0.9% normal salineDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | .25 mg/kg TSC Receives: Drug: Trans sodium crocetinate (TSC) |
| 2 | Experimental | .5 mg/kg TSC Receives: Drug: Trans sodium crocetinate (TSC) |
| 3 | Experimental | .75 mg/kg TSC Receives: Drug: Trans sodium crocetinate (TSC) |
| 4 | Experimental | 1.0 mg/kg TSC Receives: Drug: Trans sodium crocetinate (TSC) |
| 5 | Experimental | 1.25 mg/kg TSC Receives: Drug: Trans sodium crocetinate (TSC) |
| 6 | Experimental | 1.5 mg/kg TSC Receives: Drug: Trans sodium crocetinate (TSC) |
| 7 | Experimental | 1.75 mg/kg TSC Receives: Drug: Trans sodium crocetinate (TSC) |
| 8 | Experimental | 2.0 mg/kg TSC Receives: Drug: Trans sodium crocetinate (TSC) |
| 9 | Placebo comparator | 5.0 mL 0.9% normal saline Receives: Drug: 0.9% normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety (laboratory tests, vital signs, ECG, physical exam, pulse oximetry) and pharmacokinetic assessments
Measured: Screening, Baseline, Dose 1, Dose 2, Dose 3, Dose 4, Dose 5, 5-Day Follow-up, 14-Day Follow-up
Secondary outcomes (1)
Change in peak walking time (PWT) and claudication onset time (COT) in an exercise treadmill test
Measured: Baseline, Dose 1, Dose 5, 5-Day Follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2008 (estimated)
- Study startAug 2008
- Primary completionMar 2010
- Study completionMar 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Intermittent ClaudicationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Diffusion Pharmaceuticals Inc
- Sponsor type
- Industry (pharma, biotech, devices)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00725881
- Sponsor's protocol ID
- DP100-301
- Status last verified
- Jul 2011
- First submitted
- 29 Jul 2008
- Last updated
- 29 Jul 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 22003000
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00725881
- Acronym / sponsor ID
- DP100-301
- Conditions
- Intermittent Claudication
- Keywords
- PAD, Peripheral arterial disease, Peripheral artery disease, Intermittent claudication, IC, atherosclerosis, leg pain, walking pain
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Diffusion Pharmaceuticals IncIndustry (pharma, biotech, devices)
- Study start
- Aug 2008
- Primary completion
- Mar 2010 (actual)
- Study completion
- Mar 2010 (actual)
- First posted
- 31 Jul 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Trans sodium crocetinate (TSC).25 mg/kg TSC |
| 2 | Experimental | Drug: Trans sodium crocetinate (TSC).5 mg/kg TSC |
| 3 | Experimental | Drug: Trans sodium crocetinate (TSC).75 mg/kg TSC |
| 4 | Experimental | Drug: Trans sodium crocetinate (TSC)1.0 mg/kg TSC |
| 5 | Experimental | Drug: Trans sodium crocetinate (TSC)1.25 mg/kg TSC |
| 6 | Experimental | Drug: Trans sodium crocetinate (TSC)1.5 mg/kg TSC |
| 7 | Experimental | Drug: Trans sodium crocetinate (TSC)1.75 mg/kg TSC |
| 8 | Experimental | Drug: Trans sodium crocetinate (TSC)2.0 mg/kg TSC |
| 9 | Placebo comparator | Drug: 0.9% normal saline5.0 mL 0.9% normal saline |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (32 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Drug | 1, 2, 3, 4, 5, 6, 7, 8 |
| 0.9% normal salineA 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. | Drug | 9 |
Primary outcome
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
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2011.
- Derived from this study: PubMed 22003000Mohler 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.
Related trials for Intermittent Claudication
Not yet recruiting
Daily Stretching to Improve Walking in Older Patients With Peripheral Artery Disease: The STRETCH PAD Study
Peripheral Artery Disease (PAD), Intermittent Claudication
Recruiting
EVERO Drug-coated Balloon (DCB) Randomized Trial
Peripheral Vascular Disease, Peripheral Arterial Disease
Recruiting
Personalised Multicomponent Exercise Programme in Peripheral Arterial Disease
Peripheral Arterial Disease, Intermittent Claudication
Active, not recruitingPhase 4
Ramipril Treatment of Claudication: Oxidative Damage and Muscle Fibrosis
Peripheral Arterial Disease
RecruitingPhase 3
Improving Mobility After Revascularization in Peripheral Artery Disease
Peripheral Artery Disease, Intermittent Claudication
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Trans sodium crocetinate (TSC) and 0.9% normal saline in people with Intermittent Claudication, run by Diffusion Pharmaceuticals Inc at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jul 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00725881, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2011.