Zibotentan, an Endothelin Receptor Antagonist, Patients With Intermittent Claudication

NCT01890135 | Completed Phase 2 DMC

• 1 other identifier: 17030
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

Peripheral artery disease (PAD) is a major complication of atherosclerosis when blockages in the arteries to leg reduce blood flow and one of the resulting problems is termed intermittent claudication (IC). IC is leg pain with walking that is relieved with rest and IC is the most frequent clinical manifestation of PAD and it effects millions of Americans. The number of patients with, and the health care costs of, PAD will increase as the prevalence of PAD is associated with advancing age, diabetes, and smoking. Zibotentan (ZD4054) is an endothelin receptor A (ETA) blocker that undergone extensive human testing and has been shown to be safe in several patient population. There is ample evidence to suggest that an ETA blocker could improve blood flow to the legs in patients with PAD. In a study that will be funded by the National Institute of Health, the investigators will test the ability of this medication to allow better blood flow to the legs of patients with PAD. In patients with IC, the investigators will test the ability of ZD4054 to improve leg blood flow using a non-invasive imaging technique. In parallel the study will test for the ability of patients with leg pain to walk further and feel better.

Conditions

Peripheral Arterial Disease; Intermittent Claudication

Keywords

randomized; double blind; blood flow; muscle perfusion; safety

Outcome Measures

Primary Outcomes (1)

• Change in exercise-induced calf muscle perfusion by magnetic resonance imaging

  Baseline and 12 weeks

Secondary Outcomes (3)

• Change in peak walking time

  Baseline and 12 weeks

• Change in quality of life measures

  Baseline and 12 weeks

• Safety

  Baseline and Day 30

Other Outcomes (2)

• Change in ankle-brachial blood pressure index (ABI

  Baseline and 12 weeks

• Change in hematocrit

  baseline and day 30

Study Arms (2)

endothelin receptor antogonist

ACTIVE COMPARATOR

10 mg of zibotentan

Drug: Zibotentan (ZD4054); Drug: placebo

placebo

PLACEBO COMPARATOR

matched placebo

Drug: Zibotentan (ZD4054); Drug: placebo

Interventions

Zibotentan (ZD4054) DRUG

10 mg

endothelin receptor antogonist; placebo

placebo DRUG

randomized double blind

Also known as: matched placebo

endothelin receptor antogonist; placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>40 years. Patients less than 40 years of age could well have a form or "thromboangitis obliterans" often called Berger's Disease and the investigators wish to enroll only subjects with atherosclerotic vascular disease.
• Currently taking all standard medications that are part of the "good medical care" for patients with PAD including an anti-platlet agent, an angiotensin-converting enzyme inhibitors or receptor blockers, beta-blockers if indicated for ischemic heart disease, and cholesterol lowering therapy; unless documented contra-indications to these therapies exist. Those patients not on these therapies will be referred back with the suggestion that they be added and they can be re-approached for enrollment at a later date.
• Exercise induced thigh, calf, buttock pain and absence of Rutherford Class IV, V, or VI.3
• A resting ABI of \<0.9 but \>0.4 and the presence of both superficial femoral artery stenosis (70% or greater) disease and below the knee disease with a significant stenosis in at least one of the run-off vessels.
• Absence of critical inflow (iliac or common femoral) disease. The profunda femoral artery is the major source of collateral blood vessels. The investigators initial approach will be to try and enroll as homogenous of a patient population as possible to allow us to focus on the primary endpoint of the study (the change in muscle perfusion to the ischemic limb over time).
• Ability to undergo magnetic resonance imaging and provide informed written consent.

You may not qualify if:

• Serious known concomitant disease with life expectancy of less than one year
• Prior amputation or history of critical limb ischemia
• Creatinine clearance (CrCl) \>45 to permit safe administration of the gadolinium contrast agent.
• Recent myocardial infarction, unstable angina, stroke or transient ischemic attack within 3 months.
• American Heart Association Class III or IV congestive heart failure or known left ventricular ejection fraction less than 40%.
• Known history of anemia

Sponsors & Collaborators

• University of Virginia: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

University Of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Peripheral Arterial Disease; Intermittent Claudication

Interventions

ZD4054

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Brian H Annex, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, Chief Division of Cardiovascular Medicine

Study Record Dates

• First Submitted: June 18, 2013
• First Posted: July 1, 2013
• Study Start: June 1, 2013
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: August 2, 2016

Record last verified: 2016-08

Locations

US (1)