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).