diabetes mellitus ischemic heart disease
Conditions
Interventions
RVX000222 will be administered orally with food at a dose of 200 mg daily (100
mg b.i.d.).
In certain situations the dose may be decreased to 100 mg daily (50 mg b.i.d.)
Coronary Artery Disease
High-Risk Type 2 Diabetes Mellitus
Major Adverse Cardiovascular Events
Sponsors
Resverlogix
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Male and female subjects age 18 and over with documented diagnosed T2DM and a CAD event of either unstable angina or myocardial infarction, not less than 7 days and no more than 90 days prior to Visit 1. In order to have sufficient number of clinical events, the number of subjects with unstable angina will be limited to 25% of the total number of subjects - Unstable angina: for a qualifying unstable angina event, each of components (a), (b), and (c) must be satisfied: a. Characteristic ischemic pain or discomfort in chest or associated referral areas, occurring at rest or with minimal exertion b. ECG changes consistent with acute myocardial ischemia based upon at least one of the following: i. new or presumed new ST elevation ii. new or presumed new ST depression iii. new or presumed new T-wave inversion c. Objective evidence of obstructive coronary artery disease based upon at least one of the following: i. new or presumed new evidence of myocardial ischemia or infarction by perfusion imaging ii. new or presumed new regional wall motion abnormality iii. current evidence of at least one epicardial coronary artery stenosis *70% by coronary angiography iv. need for coronary revascularization related to index ACS event including percutaneous cornary intervetnion (PCI) with or without coronary stenting * Previous MI 7-90 days before screening treated with or without a percutaneous coronary intervention (PCI). For a qualifying event of MI, two of the following three criteria must be satisfied: a. Characteristic ischemic chest pain or pain in associated referral areas b. Dynamic elevation of troponin T or I or CKMB, if troponin T or I is unavailable at the local lab (at least above the upper limit of normal for the laboratory) c. Development of new Q-waves in at least two adjacent electrocardiogram (ECG) leads or development of a new dominant R wave in V1 2. Documented diagnosis of T2DM (one or more of the following criteria must be met): * Documented history of T2DM * History of taking diabetes medication * HbA1c *6.5% at Visit 1 3. For males HDL-C of
Exclusion criteria
Exclusion criteria: 1. Heart disease which, in the opinion of the investigator, will within 90 days of Visit 1 likely require coronary bypass, PCI, cardiac transplantation, surgical repair and/or replacement. 2. Previous or current diagnosis of severe heart failure (New York Heart Association Class IV) or a documented left ventricular ejection fraction (LVEF) of 100 beats per minute at rest within 4 weeks prior to Visit 1. 4. Coronary artery bypass grafting (CABG) within 90 days prior to Visit 1. 5. Evidence of severe renal impairment as determined by any one of the following: * an eGFR 180 mm Hg or diastolic >100 mm Hg at Visit 1. 7. Current or recent (within 12 months prior to Visit 1) treatment with immunosuppressants (e.g., cyclosporine). 8. Use of fibrates at any dose or niacin/nicotinic acid 250 mg or more within 30 days prior to Visit 1. 9. A known allergy or sensitivity to any ingredient in the investigational medicinal product. 10. History of intolerance to atorvastatin or rosuvastatin. This exclusion criterion applies to subjects with a history of intolerance to the statin to which they would be assigned at screening. 11. Triglycerides >400 mg/dL (4.52 mmol/L) at Visit 1. 12. Any medical or surgical condition which might significantly alter the absorption, distribution, metabolism or excretion of medication including, but not limited to any of the following: untreated or incompletely treated thyroid dysfunction, cholecystitis, Crohn*s disease, ulcerative colitis, or any gastric bypass alteration. 13. Evidence of cirrhosis from liver imaging or biopsy, a history of hepatic encephalopathy, esophageal or gastric varices, active hepatitis, or prior porta-caval shunt procedure, or a Child-Pugh score of at least 5 points. * Any one of the following liver enzymes that is >1.5x the upper limit of normal range (ULN) by central lab at Visit 1 a. Alanine aminotransferase (ALT) b. Aspartate aminotransferase (AST) 14. A total bilirubin that is >ULN by central lab at Visit 1. 15. History of malignancy of any organ system, treated or untreated, within the past 2 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin. 16. History or evidence of drug or alcohol abuse within 12 months of Visit 1, in the opinion of the investigator. 17. Female subjects who are pregnant. 18. Any condition which, in the opinion of the investigator, may place the subject at higher risk from his/her participation in the study, or is likely to prevent the subject from complying with the requirements of the study or completing the study. 19. Use of other investig
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time from randomization to the first occurrence of adjudication-confirmed MACE narrowly defined as a single composite endpoint of CV Death or Non-fatal MI or Stroke. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Time from randomization to the first occurrence of adjudication-confirmed MACE broadly defined between treatment groups. Broadly defined MACE is the occurrence of any of the following events: * CV death * Non-fatal MI * Hospitalization for CVD events which include: o Unstable angina AND evidence of new or presumed new progressive obstructive coronary disease, OR o Emergency revascularization procedures at any time and urgent revascularization procedures *30 days after the index events prior to randomization * Stroke 2. Time from randomization to fatal or non-fatal MI, or fatal or non-fatal stroke 3. Time from randomization to CV Death or Non-fatal MI 4. Time from randomization to Non-fatal MI 5. Time from randomization to CV Death 6. Time from randomization to Stroke 7. All-cause mortality | — |
Countries
Argentina, Belgium, Bulgaria, Croatia, Germany, Hungary, Israel, Mexico, Netherlands, Poland, Russian Federation, Serbia, Slovakia, Taiwan (Province of China)
Outcome results
None listed