SB-480848 In Subjects With Coronary Heart Disease

A multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study of SB-480848, an oral lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, in subjects with stable coronary heart disease (CHD) or CHD-risk equivalent to examine chronic inhibition of Lp-PLA2, effects on circulating biomarkers associated with cardiovascular risk, safety and tolerability over 12 weeks

Inclusion criteria

• Female subjects must be of non-childbearing potential.
• Stable CHD or CHD-risk equivalent.
• Must have been on a stable dose of a statin for =4 weeks with LDL <130 mg/dL (3.4 mmol/L) or off statin therapy for =4 weeks with LDL <160 mg/dL (4.1 mmol/L).
• On a stable dose of at least one oral antiplatelet agent (e.g., aspirin, clopidogrel, or ticlopidine).

Exclusion criteria

• Recent cardiovascular event and / or vascular procedure.
• History of difficult to manage dyslipidemia.
• Planned cardiac surgery or PCI (percutaneous coronary intervention) or planned major non-cardiac surgery.
• Inadequately controlled hypertension.
• Poorly controlled diabetes mellitus.
• Serum triglycerides >400 mg/dL (4.52 mmol/L).
• Recent or ongoing acute infection.
• History of chronic inflammatory disease.
• Receiving topical, oral, inhaled or injectable corticosteroids.
• History of chronic viral hepatitis, or other chronic hepatic disorders.
• History of kidney transplant.
• History of myopathy or inflammatory muscle disease, or elevated total serum CK (3 x ULN).
• Severe heart failure (NYHA class III or IV), or severe left ventricular dysfunction (ejection fraction <30%).
• Asthma manifested by bronchospasm in the past 6 months, or currently taking inhaled bronchodilator on regular basis.
• History of anaphylaxis, anaphylactoid reactions or severe allergic responses within the past 6 months.
• Malignancy within the past 2 years, other than non-melanoma skin cancer.
• Current life-threatening condition other than vascular disease that may prevent a subject from completing the study.
• QTc interval >440 msec (males) or >450 msec (females).
• Alcohol or drug abuse within the past 6 months.
• Previous exposure to SB-480848.
• Use of an investigational drug within 30 days or 5 half-lives (whichever is the longer) preceding the first dose of study medication (blinded atorvastatin).