Clinical trial NCT00445159: UT-15C SR in the Treatment of Critical Limb Ischemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Critical Limb Ischemia
Keywords: UT-15C SR, Peripheral Vascular Disease, treprostinil
Lead sponsor: Southern Arizona Vascular Institute
Sponsor class: OTHER
Collaborators: name: Southern Illinois University
First posted: 2007-03-08
Enrollment: 20
Sex: ALL
Minimum age (years): 45
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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 .

Eligibility criteria: Inclusion Criteria:

1. 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.
2. Have been taking analgesics to control ischemic rest pain for at least two weeks at Baseline.
3. Have signed an appropriate consent for participation in this study.
4. If female, be physiologically incapable of childbearing or practicing acceptable methods of birth c

Exclusion Criteria:

1. Have had a vascular surgery or other vascular procedure to treat their CLI within 30 days prior to study entry.
2. Have a planned or scheduled vascular surgery or endovascular procedure.
3. Be currently taking any investigational drugs for CLI.
4. Have received prostaglandins such as PGE1, epoprostenol (Flolan®), or any other prostacyclin (PGI2) or prostacyclin analog in the past 30 days.
5. Be hemodynamically unstable or have acute renal failure, cardiac failure or pulmonary failure.
6. Have a diagnosis of Stage IVb (Fontaine) or Stage 6 (Rutherford scale) Critical Limb Ischemia due to documented peripheral arterial disease
7. Have an unhealed incision(s) from a toe or transmetatarsal amputation at Baseline.
8. Have any wound with significant gangrene or exposed tendons.

Primary outcomes:
measure: To assess the tolerability and safety of UT-15C tablets in subjects with critical limb ischemia (CLI) and ischemic rest pain
Secondary outcomes:
measure: To assess the effect of UT-15C on the following disease symptoms associated with CLI:
measure: ž Ischemic rest pain
measure: ž Sleep interference
measure: ž Ambulatory status
measure: ž Ischemic wound healing (if applicable)
measure: To obtain peak and trough treprostinil plasma levels in CLI subjects
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Southern Arizona Vascular Institute
state: Arizona
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
Study officials:
affiliation: Southern Illinois University
name: Colleen Johnson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Southern Arizona Vascular Institute
name: Scott S Berman, MD
role: PRINCIPAL_INVESTIGATOR
References: