Clinical Trial of Manganese-Enhanced MRI (MEMRI) to Assess Peri-Infarct Injury

Clinical Trial of Manganese-Enhanced MRI (MEMRI) to Assess Peri-Infarct Injury

The purpose of this study is to evaluate the safety and tolerance of a new intravenous diagnostic agent, SeeMore or EVP 1001-1, in patients with Cardiovascular Disease (MEMRI scan). The initial phase of this study, NCT01989195 enrolling a total of 6 patients, has been closed. This second phase adds 10 patients in a safety cohort and 60 additional patients for a total of 70 patients.

This is an open-label, baseline-controlled study to be conducted. Adult male or nonpregnant female patients who have been referred for evaluation of dilated cardiomyopathy, ischemic cardiomyopathy, non-ischemic cardiomyopathy, atrial arrhythmia and also patients who have received stem cell therapy related to both ischemic and dilated cardiomyopathy (under different trials) will be recruited. An initial cohort study of 6 patients to conduct safety evaluation was conducted before proceeding with 60 additional patients. In the initial cohort, a patient was dosed based on the Phase 1 and 2 clinical trial data evaluation completed by Eagle Vision Pharmaceutical, Inc. Subjects were excluded if they had received an investigational device within 30 days prior to administration of EVP1001-1; had a history of drug abuse or alcoholism; were taking a digitalis preparation; had a history of torsades; had New York Heart Association (NYHA) Grade IV heart failure; had abnormal liver function tests or a history of liver disease; had uncontrolled hypertension; had abnormal calcium, potassium or hemoglobin values at baseline; if they develop a cardiac arrhythmia prior to or during either of the exercise tests-- EVP1001-1 was not administered. The same parameters will apply to the new group of subjects.

Prior to entry into this study, all subjects will sign an Informed Consent and will undergo a physical examination including medical history, details regarding their cardiac history, prescription and over-the-counter drug questionnaire, vital signs, electrocardiogram (ECG), evaluation of the major organ systems, hematology, serum chemistries, and urinalysis. In addition, female subjects will undergo a serum pregnancy test.

Starting 30 minutes before the cardiac MRI scan (CMR), the subjects will take a 16 mg tablet of ondansetron by mouth. CMR imaging will subsequently take place and then EVP1001-1 will then be administered approximately 15 minutes into the scan for contrast enhanced images. EVP1001-1 will be administered intravenously over approximately one minute. The subjects will each receive 0.28 mL/kg of EVP 1001-1. All subjects will be monitored closely from before ondansetron administration until their discharge from the imaging center. Following MEMRI, delayed-enhanced MRI (DEMRI scan) is performed using 0.2 mmol/kg.

We will compare the two different contrast enhanced images (EVP1001-1 vs gadolinium (GD)) in determining the non-viable (infarct core), peri-infarct, and total infarct size of myocardial tissue.

Inclusion Criteria:

All subjects to be entered must:

• be at least 18 years of age.
• if female, be nonpregnant as evidenced by a serum pregnancy test and using a medically-approved method of birth control, or post-menopausal or surgically sterile
• provide written informed consent after having received oral and written information about the study
• be in stable health based on medical history, examination and tests

Exclusion Criteria:

have a positive pregnancy test (females)

• received an investigational drug or device within 30 days prior to administration of SeeMore
• have known hypersensitivity to ondansetron or other selective serotonin 5HT3 receptor blockers
• have a history of drug abuse or alcoholism
• are taking a digitalis preparation or calcium channel blocker
• have a history of torsades or prolonged QT/QTc interval
• have NYHA Grade IV heart failure
• have abnormal liver function tests or a history of liver disease
• have uncontrolled hypertension (Systolic Blood Pressure > 140 or Diastolic BP > 90 consistently at baseline)
• have abnormal baseline potassium or calcium values or hemoglobin less than 10 g/dl
• are noncompliant or otherwise unlikely to perform as required by the protocol
• have pretest likelihood of CAD for which the requisite number of subjects have been entered
• develop an arrhythmia prior to or during either of the exercise tests; SeeMore should not be administered.