A Phase III Multi-Center, Double-Blind, Randomized, Parallel Group, up to Placebo- Controlled Clinical Trial in High-Risk Type 2 Diabetes Mellitus (T2DM) Subjects with Coronary Artery Disease (CAD) to Determine Whether Bromodomain Extraterminal Domain (BET) Inhibition Treatment with RVX000222 Increases the Time to Major Adverse Cardiovascular Events (MACE)

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 <40 mg/dL (1.04 mmol/L) and for females HDL-C of <45 mg/dL
(1.17 mmol/L) at Visit 1.
4. In the opinion of the Investigator, subjects currently not on high intensity statin therapy
will be able to start rosuvastatin according to the protocol at Visit 1.
5. In the opinion of the Investigator, subjects currently on statin therapy other than
atorvastatin or rosuvastatin can be switched to rosuvastatin according to the protocol at
Visit 1. High intensity statin therapy doses should remain unchanged during the study
period if at all possible.
6. Female subjects must meet one of the following:
* If of childbearing potential, female subjects must have a negative urine pregnancy
test and be willing and able to use medically acceptable non-hormonal method of
birth control (non-hormonal intrauterine device, condom, or diaphragm) or remain
abstinent from Screening until Follow-up Visit.
* Be of non-child-bearing potential: post-surgical sterilization or post-menopausal.
7. Have given signed informed consent to participate in this study.

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 <25% as
determined by contrast left ventriculography, radionuclide ventriculography or
echocardiography. The absence of a LVEF measurement in a subject without a
previous or current diagnosis of heart failure does not prohibit entry into the study.
3. Subjects with evidence of cardiac electrophysiologic instability including a history of
uncontrolled ventricular arrhythmias, uncontrolled atrial fibrillation/flutter or uncontrolled
supraventricular tachycardias with a ventricular response heart rate 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 <30 mL/min/1.7m2 at Visit 1
* a current need for dialysis
6. Uncontrolled hypertension defined as 2 consecutive measurements of sitting blood
pressure of systolic >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 investigational drugs and devices within 30 days or 5 half-lives of Visit 1,
whichever is longer.
20. History of noncompliance with medical regimens or unwillingness to comply with the
study protocol.
21. Any condition that, in the opinion of the investigator, would confound the evaluation
and interpretation of efficacy and/or safety data.
22. Persons directly involved in the execution of this protocol.