SB-480848 In Subjects With Coronary Heart Disease - Full Text View

Purpose

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.

Condition	Intervention	Phase
Atherosclerosis	Drug: SB-480848 Drug: placebo	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Participant, Care Provider) Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Coronary Artery Disease Heart Diseases

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

On treatment sustained inhibition of plasma Lp-PLA2 activity. [ Time Frame: 12 Weeks ]

Secondary Outcome Measures:

Difference in dose-dependent effects of SB-480848 on plasma Lp-PLA2 activity, other biomarkers, and safety. [ Time Frame: 12 Weeks ]


Enrollment:	969
Study Start Date:	November 2005
Study Completion Date:	September 2006
Primary Completion Date:	September 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm 1 SB-480848	Drug: SB-480848 SB-480848
Placebo Comparator: Arm 2 placebo	Drug: placebo placebo

Detailed Description:

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

Eligibility


Ages Eligible for Study:	18 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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).

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00269048

Show 120 Study Locations

Sponsors and Collaborators

GlaxoSmithKline

Investigators


Study Director:	GSK Clinical Trials	GlaxoSmithKline

More Information

Additional Information:

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. This link exits the ClinicalTrials.gov site