Coronary artery disease narrowing coronary
Conditions
Interventions
Following randomization, patients will receive RVX000222 at a dose of 200 mg
daily or matching placebo daily for 26 weeks along with standard therapies.
Clinical safety will be evaluated at each vis
Sponsors
Resverlogix Corp.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Male and female patient's >=18 years of age who are scheduled to undergo coronary angiography for a clinical indication. 2. Women of child-bearing potential, that is, women not surgically sterilized and between menarche and 1 year post menopause, must test negative for pregnancy at the time of enrollment based on a serum pregnancy test and agree to use a reliable method of birth control (for example, use of oral contraceptives or Norplant®; a reliable barrier method of birth control (diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam; intrauterine devices; partner with vasectomy; or abstinence) during the study and for one month following the last dose of study drug. 3. Current (Local lab within 30 days prior to Visit 1) HDL-C of 20% reduction in lumen diameter by angiographic visual estimation or prior history of PCI. - This vessel need not be the target coronary artery for IVUS. - Any vessel with previous PCI may not be used as the target coronary artery. B. Left Main Coronary Artery: - Must not have a > 50% reduction in lumen diameter by visual angiographic estimation. C. Target Coronary Artery for IVUS - Must be accessible to the IVUS catheter. - Must have a 50%, provided that the branch in question is not a target for PCI or CABG. - Has not undergone prior percutaneous coronary intervention or coronary artery bypass graft surgery. - The target vessel is not currently a candidate for intervention or a likely candidate for intervention over the next 6 months. - The target vessel may not be a bypass graft. - The target vessel may not be a bypassed vessel. - The target vessel may not be the culprit vessel for a previous MI. 7. Have given signed informed consent to participate in this study.
Exclusion criteria
Exclusion criteria: 1. Clinically significant heart disease which will require coronary bypass, PCI, cardiac transplantation, surgical repair and/or replacement during the course of the study. 2. Any elective surgical procedure that would require general anesthesia during the course of the study 3. Coronary artery bypass graft (CABG) procedure within the past 90 days. 4. Previous or current diagnosis of severe heart failure (NYHA Class IIIIV) or a documented left ventricular ejection fraction (LVEF) of 100 beats per minute at rest within 4 weeks prior to Visit 1. 6. Evidence of renal impairment as determined by any one of the following: serum creatinine >1.5 mg/dL (>133 mcmol/L) by central lab at Visit 1, a calculated creatinine clearance less than 60 ml/min at Visit 1, a history of dialysis, or a history of nephrotic syndrome. 7. Have hypertension that is uncontrolled defined as 2 consecutive measurements of sitting blood pressure of systolic >160 mm Hg or diastolic >95 mm Hg at Visit 1. 8. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive ß-hCG laboratory test (>=5 mIU/mL). 9. Current or recent (within 12 month prior to Visit 1) treatment with immunosuppressants (eg, Cyclosporine). 10. Use of fibrates any dose or niacin/nicotinic acid 250 mg or more within 90 days prior to Visit 1. 11. Atorvastatin >40 mg daily at Visit 1 12. Rosuvastatin >20 mg daily at Visit 1 13. Triglycerides >400 mg/dL at Visit 1. 14. 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: cholecystitis, Crohn's disease, ulcerative colitis, or any gastric bypass alteration. 15. Evidence of hepatic disease as determined by any one of the following: - ALT, AST, GGT that is >ULN by central lab at Visit 1 - a history of hepatic encephalopathy - history of Hepatitis B, C or E - history of esophageal varices - history of porta-caval shunt. Any one of the following liver enzymes that is >ULN by central lab at Visit 1 .ALT .AST .GGT 16. A total bilirubin that is >ULN by central lab at Visit 1 17. History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin. 18. History or evidence of drug or alcohol abuse within the last 12 months. 19. Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study. 20. Use of other investigational drugs and devices at the time of enro
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The nominal change in percent atheroma volume (PAV) from baseline to 26 weeks post-randomization, as determined by intravascular ultrasound (IVUS) within the RVX000222 treated group. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints - Nominal change in percent atheroma volume (PAV), from baseline to 26 weeks post-randomization, as determined by intravascular ultrasound (IVUS) within the RVX000222 treated group compared to placebo. - Nominal change in total atheroma volume (TAV) from baseline to 26 weeks post-randomization, as determined by intravascular ultrasound (IVUS) in the RVX000222 treated group as well as compared to placebo. - Nominal change in total atheroma volume (TAV) for the 10-mm sub-segment with the greatest disease burden at baseline, within the RVX000222 treated group as well as compared to placebo. - Proportion of patients with regression of coronary atherosclerosis, defined as a change in percent atheroma volume (PAV) from baseline to 26 weeks of less than zero (i.e. any reduction in PAV). - Percent change from baseline in HDL-C, apoA-I, and HDL-subclasses at various time points within the RVX000222 treated group as well as compared to placebo. - Incidence of adverse events by treatment group, including major adverse cardiac events (MACE) (death, MI, stroke, coronary revascularization, hospitalization for ACS or heart failure). Exploratory Endpoints - Correlations between changes in atheroma burden (PAV and TAV) and percent change in lipid biomarkers (HDL-C, apoA-I, HDL-subclasses). - Change in features of plaque composition by intravascular imaging within the RVX000222 treated group as well as compared to placebo on a subset of patients. - Evaluations of Pharmacokinetics trough values (C-min) at various time points. | — |
Countries
Netherlands
Outcome results
None listed