Resumen

This trial of SB-480848 in approximately 920 subjects with Coronary Heart Disease (CHD) or CHD-risk equivalent will examine whether SB-480848 produces sustained inhibition of plasma Lp-PLA2 activity, explore the effects of SB-480848 on other circulating biomarkers associated with cardiovascular risk, and evaluate the pharmacokinetics, safety and tolerability of SB-480848 over 12 weeks of once-daily oral dosing. Subjects will first be randomized 1:1 to double-blind atorvastatin 20 mg or 80 mg once daily for a minimum of 3 weeks. Subjects will then be randomized 1:1:1:1 to oral doses of SB-480848 40 mg, 80 mg, 160 mg or placebo once daily for 12 weeks. Blood samples will be collected at various timepoints. Vital signs, electrocardiograms, clinical laboratory safety tests and adverse event assessments will be performed to evaluate the safety and tolerability of SB-480848.

Descripción detallada

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

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 80 YearsSexo: ALL

Criterios de inclusión

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).

Criterios de exclusión

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).

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

SB-480848

placebo

Ubicaciones

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

Patrocinadores