Effect of RVX000222 on Time to Major Adverse Cardiovascular Events in High-Risk T2DM Subjects With CAD

• Status: Completed
• Trial end date: 2021-06-21
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Resverlogix Corp
• Collaborators: ICON plc; Medidata Solutions; PPD
• Treatments: Atorvastatin; Atorvastatin Calcium; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium

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