SB-480848 In Subjects With Coronary Heart Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 15 August 2016
• Main ID: NCT00269048
• Date of registration: 21/12/2005
• Prospective Registration: No
• Primary sponsor: GlaxoSmithKline
• Public title: SB-480848 In Subjects With Coronary Heart Disease
• Scientific 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
• Date of first enrolment: November 2005
• Target sample size: 969
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00269048
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

Argentina, Australia, Bulgaria, Canada, Denmark, Estonia, France, Germany, Hungary, India, Netherlands, New Zealand, Pakistan, Romania, Spain, United Kingdom, United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion 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).



Age minimum: 18 Years
Age maximum: 80 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Atherosclerosis

Intervention(s)

Drug: SB-480848

Drug: placebo

Primary Outcome(s)

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

Secondary Outcome(s)

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

Secondary ID(s)

LPL104884

Source(s) of Monetary Support

Please refer to primary and secondary sponsors