Secondary cardiovascular disease (CVD) prevention in type 2 diabetes mellitus (T2DM) subjects with low high-density lipoprotein cholesterol (HDL-C) at high risk for MACE. MedDRA version: 19.0 Level: LLT Classification code 10051614 Term: Arteriosclerotic cardiovascular disease System Organ Class: 100000004866 MedDRA version: 19.0 Level: LLT Classification code 100516
Conditions
Interventions
Product Name: RVX000222
Product Code: RVX000222
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: INN not yet assigned
Current Spo
Sponsors
Resverlogix Corp.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female subjects age 18 and over with documented diagnosed T2DM and a CAD event not less than 7 days and no more than 90 days prior to Visit 1 (one or more of the following three primary criteria must be satisfied): - 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 - History of percutaneous coronary intervention (PCI) with or without coronary stenting to treat acute coronary syndrome 7-90 days before Visit 1. - Previous MI 7-90 days before screening. Two of the following three criteria must be satisfied: a. Characteristic ischemic chest pain or pain in associated referral areas, b. Elevation of troponin T or I 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 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: a. 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 (nonhormonal intrauterine device, condom, or diaphragm) or remain abstinent from Screening until Follow-up Visit. b. Be of non-child-bearing potential: post-surgical sterilization or post-menopausal. 7. Have given signed informed consent to participate in this study. Are the trial subjects under 18? no
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 estimated Glomerular Filtration Rate less than 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. 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 (Appendix A) - Any one of the following liver enzymes that is >1.5xULN by central lab at Visit 1 i. ALT ii. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate if treatment with RVX000222 as compared to placebo increases time to the first occurrence of narrowly defined MACE. Narrowly defined MACE is defined as a single composite endpoint of CV death or Non-fatal MI or Stroke.; Secondary Objective: - To evaluate if treatment with RVX000222 increases time to the first occurrence of broadly defined MACE in comparison to placebo - To evaluate treatment group difference in all-cause mortality - To evaluate changes in lipoprotein concentrations including apoA-I, apolipoprotein B (apoB), LDL-C, HDL-C, and triglyceride (TG) over time within and between treatment groups - To evaluate changes in DM variables including glycated hemoglobin (HbA1c), fasting glucose, and fasting insulin over time within and between treatment groups - To evaluate changes in ALP over time within and between treatment groups including isoforms for whole population and quartiles of ALP baseline concentration - Assess changes in kidney function in population with baseline estimated glomerular filtration rate <60 mL/min/1.7m2 - To evaluate the safety and tolerability of RVX000222 ;Primary end point(s): The primary endpoint will be 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.;Timepoint(s) of evaluation of this end point: Primary endpoints will be assessed until end of study treatment (104 weeks) or when the 250th event occurs, whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 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 CV Death or Non-fatal MI 3. Time from randomization to Non-fatal MI 4. Time from randomization to CV Death 5. Time from randomization to Stroke 6. All-cause mortality Other secondary endpoints: - The percent change in apoA-I, apoB, LDL-C, HDL-C, and TG over time within and between treatment groups - The change from baseline in HbA1c, fasting glucose, and fasting insulin within and between treatment groups - Changes in ALP within and between treatment groups for all subjects and according to quartiles of ALP baseline concentration - Changes from baseline in kidney function in subgroup population with estimated glomerular filtration rate <60 mL/min/1.7m2 within and between treatment groups ;Timepoint(s) of evaluation of this end point: Secondary endpoints will be assessed until end of study treatment (104 weeks) or when the 250th event occurs, whichever occurs first. | — |
Countries
Argentina, Australia, Belgium, Bulgaria, Croatia, Germany, Hungary, Israel, Mexico, Netherlands, Poland, Serbia, Slovakia
Contacts
Public ContactClinical Development
Resverlogix Corp
Outcome results
None listed