Clinical trial NCT01067820 (phase 2, status: completed)
Conditions: coronary artery disease
ICD codes: I25.10, I25.110, I25.119, I25.111, I25.118
Drugs: rvx000222, placebo rvx000222
SMILES: COC1=CC2=C(C(=O)N=C(N2)C2=CC(C)=C(OCCO)C(C)=C2)C(OC)=C1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility 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 60 days prior to Visit 1). HDLC of </= 45 mg/dL (1.2 mmol/L)
             for females and HDLC of </=40 mg/dL (1.0 mmol/L) for males.

          4. In the opinion of the investigator patients currently not on statin therapy will be
             able to start either atorvastatin (10 mg, 20mg or 40mg) or rosuvastatin (5mg, 10mg or
             20 mg) at Visit 1.

          5. In the opinion of the investigator patients currently on statin therapy other than
             atorvastatin (10 mg, 20mg or 40mg) or rosuvastatin (5mg, 10mg or 20 mg) can be
             switched to rosuvastatin (5mg, 10mg or 20 mg) at Visit 1.

          6. Patients must meet all of the following criteria at the qualifying coronary
             catheterization procedure:

             A. Entire Coronary Circulation: Angiographic evidence of coronary heart disease as
             defined by at least one lesion in any of the three major native coronary arteries that
             has >20 percent 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 percent 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 percent reduction in lumen diameter by angiographic visual estimation throughout
             a segment of at least 40 mm in length (the "target segment"). A lesion of up to 60
             percent stenosis is permitted, distal to the target segment. A single branch of the
             "target vessel" may have a narrowing up to but <70 percent by visual estimation, as
             long as the target segment contains no lesion >50 percent, 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:

          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 III-IV) or a
             documented left ventricular ejection fraction (LVEF) of <25 percent as determined by
             contrast left ventriculography, radionuclide ventriculography or echocardiography, the
             absence of an LVEF measurement in a patient without a previous or current diagnosis of
             heart failure does not prohibit entry into the study.

          5. Patients 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.

          6. Evidence of renal impairment as determined by any one of the following:

               -  serum creatinine >1.5 mg/dL (>133 micromol/L) by central lab at Visit 1,

               -  a calculated creatinine clearance less than 60 ml/min at Visit 1

               -  a history of dialysis,

               -  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 beta-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: 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 enrollment, or within 30
             days or 5 half-lives of enrollment, whichever is longer.

         21. History of noncompliance to medical regimens or unwillingness to comply with the study
             protocol.

         22. Any condition that in the opinion of the investigator would confound the evaluation
             and interpretation of efficacy and/or safety data.

         23. Persons directly involved in the execution of this protocol.