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

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

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

Study Overview

• Status: Unknown
• Conditions: Critical Limb Ischemia
• Intervention / Treatment: Drug: UT-15C SR (treprostinil diethanolamine) 1mg oral tablets

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 .

• Study Type: Interventional
• Enrollment: 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85704
      • Recruiting
      • Southern Arizona Vascular Institute
      • Contact: Sonia Voigt, RN; Phone Number: 520-297-5846; Email: svoigt@azvasc.com
      • Principal Investigator: Scott S Berman, MD
  • Illinois
    • Springfield, Illinois, United States, 62794-9638
      • Recruiting
      • Southern Illinois University School of Medicine
      • Contact: Carol Buettner; Phone Number: 217-545-2320; Email: cbuettner@siumed.edu
      • Principal Investigator: Colleen Johnson, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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
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

Collaborators and Investigators

• Sponsor: Southern Arizona Vascular Institute
• Collaborators: Southern Illinois University
• Investigators: Principal Investigator: Colleen Johnson, MD, Southern Illinois University; Principal Investigator: Scott S Berman, MD, Southern Arizona Vascular Institute

Study record dates

Study Major Dates

• Study Start: November 1, 2006

Study Registration Dates

• First Submitted: March 7, 2007
• First Submitted That Met QC Criteria: March 7, 2007
• First Posted (Estimate): March 8, 2007

Study Record Updates

• Last Update Posted (Estimate): March 8, 2007
• Last Update Submitted That Met QC Criteria: March 7, 2007
• Last Verified: March 1, 2007

More Information

Terms related to this study

• Keywords: UT-15C SR, Peripheral Vascular Disease, treprostinil
• Additional Relevant MeSH Terms: Pathologic Processes; Ischemia; Antihypertensive Agents; Treprostinil
• Other Study ID Numbers: UT-15C