Effect of RVX000222 on Time to Major Adverse Cardiovascular Events in High-Risk T2DM Subjects With CAD
Condition: Diabetes Mellitus, Type 2; Coronary Artery Disease
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Apabetalone; Placebo; Atorvastatin; Rosuvastatin
Intervention description: 100 mg capsule; Capsule manufactured to mimic RVX000222 100 mg capsule; High-Intensity Statin; High-Intensity Statin
Intervention MeSH terms: Atorvastatin; Rosuvastatin Calcium
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 2425.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine whether bromodomain extraterminal domain (BET)
      inhibition treatment with RVX000222 in high-risk type 2 diabetes mellitus patients with
      coronary artery disease increases the time to major adverse cardiovascular events.
    

Eligibility criteria:

        Inclusion Criteria:

        • ACS event of either unstable angina or myocardial infarction 7-90 days prior Visit 1:

        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/associated
        referral areas, occurring at rest/with minimal exertion b.) ECG changes consistent with
        acute myocardial ischemia based on new/presumed ST elevation/depression or T-wave inversion
        c.) Objective evidence of obstructive CAD based on 1+ of the following: i. New/presumed new
        evidence of myocardial ischemia/infarction by perfusion imaging ii. New/presumed new
        regional wall motion abnormality iii. Current evidence of at least 1 epicardial coronary
        artery stenosis ≥70% by coronary angiography iv. Need for coronary revascularization for
        the index ACS event, including a percutaneous coronary intervention (PCI) with or without
        coronary stenting.

        Prior MI 7-90 days prior screening treated with or without a percutaneous coronary
        intervention (PCI). For a qualifying event of MI 2 of the following 3 criteria must be
        satisfied: a.) Characteristic ischemic chest pain/pain in associated referral areas b.)
        Dynamic elevation of troponin T/I or CKMB if troponinT/I is unavailable at local lab (at
        least >ULN for lab) c.) Development of new Q-waves in ≥2 adjacent ECG leads or development
        of new dominant R wave in V1

          -  Documented diagnosis of T2DM (1+ of the following criteria): Documented history of
             T2DM, History of taking diabetes medication, and/or HbA1c ≥6.5% at Visit 1

          -  For males HDL-C<40 mg/dL(1.04 mmol/L), for females HDL-C<45 mg/dL(1.17 mmol/L) at
             Visit 1

          -  Subjects currently not on high intensity statin therapy could start rosuvastatin at
             Visit 1 and those currently on therapy besides atorvastatin/rosuvastatin can be
             switched to rosuvastatin at Visit 1

          -  Female subjects of non-childbearing potential (post-surgical
             sterilization/post-menopausal) or if childbearing potential have neg urine pregnancy
             test and be willing and able to use non-hormonal birth control (non-hormonal IUD,
             condom or diaphragm) or remain abstinent from Screening to Follow-up Visit

          -  Give signed informed consent

        Exclusion Criteria:

          -  Heart disease which will w/in 90 days of Visit 1 likely need coronary bypass, PCI,
             cardiac transplantation, surgical repair and/or replacement

          -  Previous/current diagnosis of severe heart failure or documented LVEF<25% determined
             by contrast left ventriculography, radionuclide ventriculography or echocardiography.
             Absence of LVEF measurement in subject w/out a previous/current diagnosis of heart
             failure does not exclude entry into study

          -  Evidence of cardiac EP instability incl. history of uncontrolled ventricular
             arrhythmias, atrial fibrillation/flutter or supraventricular tachycardias w/ a
             ventricular response HR>100bpm at rest w/in 4 wks prior Visit 1

          -  CABG w/in 90 days prior Visit 1

          -  Evidence of severe renal impairment as determined by either eGFR<30 mL/min/1.7m2 at
             Visit 1 or current need for dialysis

          -  Uncontrolled hypertension defined as 2 consecutive measurements of sitting BP of
             systolic>180 mmHg or diastolic>100 mmHg at Visit 1

          -  Treatment w/ immunosuppressants w/in 12 mos prior Visit 1

          -  Use of fibrates at any dose or niacin/nicotinic acid 250+ mg w/in 30 days prior Visit
             1

          -  Known allergy/sensitivity to any ingredient in IMP

          -  History of intolerance to atorvastatin/rosuvastatin

          -  Triglycerides>400 mg/dL (4.52 mmol/L) at Visit 1

          -  Any medical/surgical condition which might significantly alter absorption,
             distribution, metabolism or excretion of medication

          -  Evidence of cirrhosis from liver imaging/biopsy, history of hepatic encephalopathy,
             esophageal/gastric varices, active hepatitis or prior porta-caval shunt procedure or a
             Child-Pugh score of ≥5 points

          -  ALT/AST>1.5xULN by central lab at Visit 1

          -  Tot. bilirubin>ULN by central lab at Visit 1

          -  History of malignancy of any organ syst treated/untreated w/in the past 2 yrs whether
             or not there is evidence of local recurrence/metastases except localized basal skin
             cell carcinoma

          -  History/evidence of drug/alcohol abuse w/in 12 mos of Visit 1

          -  Pregnancy

          -  Any condition which may place subject at higher risk from his/her participation in the
             study or is likely to prevent subject from completing/complying w/ requirements of
             study

          -  Use of other investigational drugs and devices w/in 30 days or 5 half-lives of Visit
             1, whichever is longer

          -  History of noncompliance to medical regimens or unwillingness to comply w/ study
             protocol

          -  Any condition that would confound the evaluation/interpretation of efficacy and/or
             safety data

          -  Persons directly involved in execution of this protocol