MIP-BP22 Phase 2 Normals and Coronary Artery Disease Database

Purpose

The purpose of this study is to develop a gender-matched normal database for the objective assessment of ischemic myocardium when using iodofiltic acid I 123, to evaluate the safety of the drug, and to use the Coronary Artery Disease patient’s imaging data to determine criteria for abnormality using the cardiac images obtained by using the drug.

Study Type: Interventional
Study Design: Diagnostic, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety Study

Official Title: Development of a Normal Database and Criteria for Abnormality for ? Methyl-p-[123I]-Iodophenyl-Pentadecanoic Acid (Iodofiltic Acid I 123) for Quantitative Imaging

Further study details as provided by Molecular Insight Pharmaceuticals, Inc.:

Primary Outcome:
Measures: an exercise treadmill test for low-likelihood for CAD subjects (normals) followed within 24 to 30 hours by images taken of the heart after injection with a single dose of iodofiltic acid I 123; for CAD patients, an exercise stress myocardial perfusion imaging scan using a radioactive dye followed within 10 days by images taken of the heart after injection with a single dose of iodofiltic acid I 123; for CAD patients only, cardiac angiography must be performed within 30 days before or after iodofiltic acid imaging.

Secondary Outcome:
Measures: medical history, physical examination, pregnancy test for females pre-dose; vital signs 2 times pre-dose; electrocardiogram 3 times pre-dose; blood and urine samples pre-dose; physical examination post-dose; vital signs 3 times post-dose; electrocardiograms 6 times post-dose; blood and urine samples post-dose monitoring for adverse events starting when the patient consents to be in the study until 2 to 4 hours post-dose, monitoring for serious adverse events starting when the patient consents to be in the study until 30 days post-dose.

Expected Total Enrollment:
Approximately 120 patients, of which about 60 are normal subjects and about 60 are CAD patients

Study start: March 2006; Expected completion: December 2006 Last follow-up: January 2007; Data entry closure: January 2007

Iodofiltic acid I 123 is a methyl-branched fatty acid that is labeled with radioactive iodine. The metabolic stability of this study drug allows retention of radioactivity in the heart long enough to allow sufficient blood clearance so that high quality planar and Single Photon Emission Computed Tomography (SPECT) imaging can be performed. This study is designed to develop a gender-matched normal database and assess the safety of iodofiltic acid I 123.

Eligibility

Ages Eligible for Study: 40 Years and above;
Genders Eligible for Study: Both

Criteria

Inclusion Criteria:

• Provide written informed consent and are willing to comply with protocol requirements.
• Are at least 40 years of age.
• If female, then not of childbearing potential as documented by history (e.g., tubal ligation, hysterectomy, or post menopausal with a minimum 1 year without menses) OR has a negative serum or urine HCG pregnancy test within 30 hours prior to receiving the test drug and agrees to use an acceptable form of birth control.

In addition, each patient must meet eligibility criteria below for either the low likelihood for CAD (Stratum L) or CAD Stratum (Stratum C).

(Stratum L) Low-likelihood for CAD (n= ~30 males and ~30 females)

• Having a lower than 5% likelihood of CAD based on sequential Bayesian analysis (Appendix A) of age, gender, symptom classification and exercise ECG results.

(Stratum C) CAD Stratum (n= ~30 males and ~30 females)

• Demonstrate a reversible perfusion defect on exercise stress MPI study. CAD patients who have previous MI and have reversible perfusion defects will be eligible for the trial, provided that the area of the reversible defect is larger than the area of the fixed defect.
• Single, double, or triple vessel disease will be documented by coronary angiography within 30 days before or after of iodofiltic acid I 123 imaging. No interventions in the interim between stress MPI or angiography imaging studies and the iodofiltic acid I 123 study. Angiographic abnormality will be defined as coronary lesions ≥ 70% or left main stenosis ≥ 50%. For a CAD imaging study to be included in the database the reversible perfusion defect must be in a vascular region supplied by a stenotic vessel.

Exclusion Criteria:

• Age < 40
• Females who are lactating
• History of left ventricular ejection fraction (LVEF) ≤ 40%
• History of coronary bypass surgery (CABG)
• Acute changes on ECG
• Left bundle branch block on ECG
• Known history of significant allergy to shellfish, X-ray contrast media or iodine/iodides that required medical intervention.
• Formerly or currently on medication that targets fatty acid uptake or metabolism, e.g., ranolazine (Ranexa™)
• Administered a radioisotope other than rubidium-82 within 2 days prior to study enrollment
• Serum creatinine level > 2.0 mg per dL
• Has received an investigational compound and/or medical device within 30 days before admission into this study
• Has any medical condition or other circumstances which would significantly decrease the chances of obtaining reliable data, achieving study objectives, or completing the study and/or postdose follow-up examinations
• Is determined by the Investigator that the patient is clinically unsuitable for the study

Location and Contact Information

This study is being conducted at 10 U.S. sites and 4 Canadian sites.
Please contact Molecular Insight Pharmaceuticals, Inc. for further information at:
clinicaltrials@molecularinsight.com