ARISE - Aggressive Reduction of Inflammation Stops Events
"Reduction of Vascular Inflammation and Coronary Atherosclerosis With AGI-1067, a V-Protectant, Reduces Cardiovascular Events in Patients With Coronary Artery Disease"
To assess the safety and efficacy of AGI-1067, as compared to placebo, in the treatment of vascular inflammation and atherosclerosis by assessing the reduction in cardiovascular events.
This study will be a Phase III multi-center, double-blind, parallel group, placebo-controlled trial involving approximately 260 study sites in the United States, Canada, South Africa and the United Kingdom. It is expected that approximately 6,600 subjects will be screened in order to randomize approximately 6,000 subjects globally (3,000 in each arm of the study). Male or female subjects with coronary artery disease are eligible to participate if they meet all required inclusion and exclusion criteria. Recruitment will be delayed for one month in subjects who have had a PCI. Subjects who have a PCI planned at the time of screening or randomization, will not be randomized until one month after this planned PCI has been conducted. All subjects who successfully complete the screening phase and meet all required inclusion and exclusion criteria will be entered into the single-blind, placebo Run-In phase of the study to establish compliance. The placebo Run-In medication will be identical to the blinded study drug used in the randomized portion of the study. After the completion of the two-week Run-In, if compliance has been adequate, study subjects will be randomized to receive AGI-1067 300 mg (two 150 mg tablets daily with a meal) or placebo (approximately equal numbers of subjects per treatment group) for a minimum of 12 months. It is anticipated that subject accrual will occur over a period of approximately 24 months and that all subjects will be followed until at least 990 subjects have experienced a primary event. Subjects will remain on drug therapy from randomization until the end of the study. It is estimated that the first subject recruited will be exposed to blinded therapy for 30 to 36 months, and the last subject will be exposed for a minimum of 6 to 12 months. For the purposes of this study one month will be equal to 28 days. The subject will be asked to return to the clinic at 1 month, 3 months, and every 3 months thereafter during the treatment phase. All clinical laboratory procedures and electrocardiographic interpretations will be performed by central laboratories. Over the study period, subjects will be followed for the occurrence of major adverse cardiovascular events. These potential endpoints will be adjudicated by an independent endpoint committee. This committee will consist of cardiologists and other physician reviewers who will be blinded to the treatment. For the purposes of safety, the trial will be monitored by an independent Data Safety Monitoring Board. This Board will consist of Cardiologists, and at least one Statistician experienced in the conduct of clinical trials. The Board will meet approximately every 6 months to review subject safety data.
IRB-approved informed written consent must be provided by all subjects prior to screening and study entry. A. Inclusion Criteria Informed written consent from the subject prior to Screening Acute MI or unstable angina not less than 14 days and not more than one year prior to randomization Male or female subjects in one of the two following groups: Subjects with diabetes mellitus (NIDDM or IDDM) 18 years of age or older Subjects (without diabetes mellitus) 55 years of age or older with one of the following additional risk factors: (i) Age 60 or older (ii) Low HDL-C as evidenced by: Male: HDL-C < 40 mg/dL or Female: HDL-C < 50 mg/dL (iii) Previous Myocardial Infarction (in addition to the index event), or diagnosis of Atherosclerosis in a non-coronary vessel (e.g. history of prior stroke, presence of PVD) (iv) Prior history of CHF (Congestive Heart Failure) or ejection fraction < 40% Females must be non-lactating and not of child bearing potential B. Exclusion Criteria Subjects who are hemodynamically or clinically unstable Subjects who have had a PCI in the last 30 days Subjects who have had coronary artery bypass (CABG) in the last 3 months Subjects on a waiting list for revascularization or revascularization already planned Current symptoms consistent with moderate or severe CHF despite medical therapy Clinically significant valvular heart disease or Hypertrophic Obstructive Cardiomyopathy Uncontrolled hypertension (e.g., sitting systolic BP > 180 mm Hg on antihypertensive therapy) Known major hematologic, renal, hepatic, metabolic, gastrointestinal or endocrine dysfunction Subjects taking and requiring continued therapy with drugs known to significantly prolong the QT interval (this will not include drugs associated with minor effect on the QT interval of less than 15 msec.) Life-threatening illness where the subject is not expected to survive for 2 years or any history of cancer or malignancy within the past 5 years except for basal cell carcinoma or squamous cell carcinoma of the skin A history of intolerance to probucol (Lorelco™) Unreliability as a study participant based on the Investigator's (or designee's) knowledge of the subject (e.g., alcohol or other drug abuse, inability or unwillingness to adhere to the protocol, or psychosis) Participation in any investigational drug study within 30 days prior to study entry, or expectation to participate in any other investigational drug study during the course of the ARISE study. Previous participation in a study involving AGI-1067