UT-15C SR in the Treatment of Critical Limb Ischemia

Study Overview
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Brief Summary
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This study will evaluate UT-15C sustained release tablets in subjects experiencing ischemic lower limb rest pain related to advanced peripheral arterial disease. Rest pain is one of the primary management issues of severe arterial occlusive disease and may lead to amputation when the pain becomes intolerable and unresponsive to narcotic analgesia. Rest pain also impacts the quality of sleep and mobility with frequent interruptions in sleep and decreased mobility. Treprostinil sodium (Remodulin®) has been studies in several small open-label studies and has been shown to be safe as well as an effective agent for ischemic rest pain when given by subcutaneous or intravenous delivery. However, these forms of administration have patient convenience limitations, including the need for an infusion device and associated pain at the site of infusion with subcutaneous delivery. UT-15C may allow patients suffering from CLI to benefit from the simplicity of an oral dosage form

Detailed Description
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This study is an eight week, two center, open-label study assessing the tolerability, safety, and efficacy of oral UT-15C sustained release tablets in subjects with CLI and ischemic lower limb rest pain, with or without an ischemic wound present. Conventional therapy should be continued without changes over the course of the study for all subjects. Group 1: The first ten subjects to enroll in the study will be assigned to receive an initial dose of 1mg. The dose will be titrated upward every seven days, depending on tolerability, to a maximum dose of 4mg/day . Group 2: The last ten subjects to enroll in the study will be assigned to receive an initial dose of 1mg. The dose will be titrated upward every seven days, depending on tolerability to a maximum dose of 8 mg/day .

Official Title
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An Investigator Initiated Eight Week Two Center Open-Label Pilot Study of the Tolerability and Safety of Oral UT-15C (Treprostinil Diethanolamine)SR Tablets in Patients With Critical Limb Ischemia (CLI) and Ischemic Rest Pain

Conditions
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Critical Limb Ischemia

Intervention / Treatment
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* Drug: UT-15C SR (treprostinil diethanolamine) 1mg oral tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have an ankle systolic pressure ≤ 60 mm/Hg OR ABI ≤ 0.60 OR toe systolic pressure ≤ 60 mm/Hg OR an arteriogram showing at least one level of occlusion of lower extremity arteries. Have been taking analgesics to control ischemic rest pain for at least two weeks at Baseline. Have signed an appropriate consent for participation in this study. If female, be physiologically incapable of childbearing or practicing acceptable methods of birth c Exclusion Criteria: Have had a vascular surgery or other vascular procedure to treat their CLI within 30 days prior to study entry. Have a planned or scheduled vascular surgery or endovascular procedure. Be currently taking any investigational drugs for CLI. Have received prostaglandins such as PGE1, epoprostenol (Flolan®), or any other prostacyclin (PGI2) or prostacyclin analog in the past 30 days. Be hemodynamically unstable or have acute renal failure, cardiac failure or pulmonary failure. Have a diagnosis of Stage IVb (Fontaine) or Stage 6 (Rutherford scale) Critical Limb Ischemia due to documented peripheral arterial disease Have an unhealed incision(s) from a toe or transmetatarsal amputation at Baseline. Have any wound with significant gangrene or exposed tendons.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: UT-15C SR (treprostinil diethanolamine) 1mg oral tablets|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the tolerability and safety of UT-15C tablets in subjects with critical limb ischemia (CLI) and ischemic rest pain |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the effect of UT-15C on the following disease symptoms associated with CLI: |  |  | 
| ž Ischemic rest pain |  |  | 
| ž Sleep interference |  |  | 
| ž Ambulatory status |  |  | 
| ž Ischemic wound healing (if applicable) |  |  | 
| To obtain peak and trough treprostinil plasma levels in CLI subjects |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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UT-15C SR, Peripheral Vascular Disease, treprostinil