This study will determine if a drug called TG100-115 can be safely administered to patients who have had a procedure, such as balloon angioplasty and stent placement, to restore blood flow following a heart attack. It also will evaluate whether TG100-115 reduces heart muscle damage in heart attacks. The results of this study will provide information to be used in the design of future studies with TG100-115.

Patients between 18 and 80 years of age who have had a stent placed in one of their coronary arteries following a heart attack may be eligible for this study. Candidates are recruited from among patients at Suburban Hospital in Bethesda, Maryland, who are participating in the TargeGen TG001-03 study.

Study participants undergo imaging with the radioactive drug Tc-99m/Sestamibi to measure the size of their heart attack. The drug is injected into a vein and a series of pictures are taken with a camera that detects the radioactivity.

Treatment or Intervention	Phase
Drug: TG100-115	Phase I

Further Study Details: 

Expected Total Enrollment:  10

This is an exploratory study designed to obtain preliminary safety and pharmacokinetic data in human subjects with the targeted disease indication. The subjects enrolled into the study will be undergoing percutaneous coronary intervention (PCI) following an acute anterior ST elevation myocardial infarction. The study is a pilot and is not powered to achieve statistical significance but is designed to provide sufficient data for the design of future studies with TG100-115. Therefore a series of endpoints are listed below which will be used to help define the primary and secondary objectives of future studies. Of particular interest will be the inter-subject variance of infarct size using the two specified methodologies which will help determine the assessment of infarct size in the pivotal studies.

The following evaluations will be performed:

Subject safety (including 24 hr and 30 [plus/minus 7] day survival).

Pharmacokinetics.

Impact of TG100-115 on infarct size using magnetic resonance imaging (MRI) at 72-144 hrs and Tc-99 Sestamibi at 120-192 hrs post-dose; both sets of measurements should be made within 48 hrs of each other.

Area of microvascular damage and stunned myocardium at 72-144 hrs post-dose, as measured by MRI.

Left ventricular (LV) function as defined by LV volumes, ejection fraction and overall contractile performance as measured by MRI at 72-144 hrs post-dose.

Left ventricular function as defined by LV volumes, ejection fraction and overall contractile performance as measured by MRI and echocardiography at 30 (plus/minus 7) days post-dose.

Serum concentrations of markers reflecting cardiac damage (to include troponin I, creatine kinase myocardial band (CKMB), myoglobin and brain natriuretic peptide), hereafter referred to as MCD.

Analysis of 12-lead ECG parameters.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
Age 18-80 yrs.
ECG with cumulative ST elevation greater than or equal to 4 mV (i.e., greater than or equal to 2 mm in at least 2 of leads I, a VL, V1-V6 or ST elevation greater than or equal to 1 mm in all 4 leads II, III V5-V6 or ST elevation greater than or eqaul to 2 mm in at least 2 of leads II, III, V5-V6).
Have prolonged signs and symptoms of myocardial ischemia not eliminated with nitrates.
Intent to proceed to primary PCI within 6 hours of chest pain onset.
Sign an informed consent form and be willing to attend follow-up visits for safety and other study assessments.
EXCLUSION CRITERIA:
Female of childbearing potential. (A female is of childbearing potential unless she has been rendered sterile by surgery or is postmenopausal. A negative pregnancy test result is required for all females for inclusion in the study).
History of previous myocardial infarction.
History of congestive heart failure.
Requirement for a cardiac pacemaker or defibrillator.
Subjects considered by the Investigator to be in cardiogenic shock(i.e., a low output state).
Myocardial ischemia precipitated by a condition other than atherosclerotic coronary artery disease (CAD; e.g. arrhythmia, severe anemia, hypoxia, thyrotoxicosis, cocaine, cardiomyopathy, severe valvular disease or hypotension).
TIMI flow = 0 or 1 in culprit, infarct-related artery post-PCI.
Any known contraindications to MRI, SPECT, or echocardiography procedures, including, but not limited to, allergies to study-specified contrast agents (i.e., Tc-99 Sestamibi, gadolinium, Optison, Definity, or Imagent), inability to lie flat for 60 minutes, body weight exceeding limitation of imaging equipment. (Department-specific contraindications for individual institutions should be obtained for screening patients).
Dementia or altered mental status that would prohibit giving conscious informed consent.
Other serious disease(s), including severe liver disease or renal failure (creatinine clearance less than 30mL/min).
Treatment with other investigational agents or devices within the previous 30 days or planned use of investigational drugs or devices within 30 days after dosing.
Subjects treated with thrombolytic therapy within the past 24 hours.
Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for this study.

Maryland
      National Heart, Lung and Blood Institute (NHLBI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  050079; 05-H-0079
Record last reviewed:  January 7, 2005
Last Updated:  April 5, 2005
Record first received:  February 23, 2005
ClinicalTrials.gov Identifier:  NCT00104208
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08