Study to Determine the Effect of 14 Days Dosing With Darapladib (SB-480848) on Carotid Plague Composition in Patients With Planned Carotid Endarterectomy

• Status: Completed
• Trial end date: 2003-07-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective is to determine Lp-PLA2 activity in atherosclerotic carotid plaques after 14 (+/-4) days treatment with darapladib, compared to placebo. Secondary objectives include determination of the change in Lp-PLA2 activity in blood, Lp-PLA2 mass in blood and plaque, specified biomarkers in blood and plaque and their respective correlation's with Lp-PLA2. In addition, the study aims to characterise the PK/PD of repeat oral doses of SB-480848, and safety and tolerability in this population.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GlaxoSmithKline

Criteria

Inclusion Criteria:

• Male or female, >35 years of age

• Females of childbearing potential must be using approved contraceptive measures

• Male patients must be willing to abstain from sexual intercourse or use a form of contraception if engaging in sexual intercourse with a woman who could become pregnant

• Planned carotid endarterectomy within a timeframe compatible with recruitment for the study and able to comply with the requirements of the study, as deemed by the investigator

• Written, informed consent to participate

Exclusion Criteria:

• Recent myocardial infarction (within the previous 4 weeks)

• Currently taking corticosteroids, warfarin, digoxin or a potent CYP3A4 inhibitor

• Recent (<3 months) or ongoing acute infection or significant trauma associated with bruising and/or taking antibiotics. Prophylactic antibiotics for surgery are allowed

• Change in dose of lipid-lowering therapy during the previous 4 weeks from randomisation

• History of chronic liver disease (e.g. cirrhosis, hepatitis) OR ALT OR AST ≥1.5 times the upper limit of normal (ULN) at screening

• Diagnosis of systemic lupus erythematosis (SLE) or rheumatoid arthritis (RA)

• Clinically significant anaemia

• History of severe renal impairment (serum creatinine >1.8mg/dL)

• Unstable angina

• History of asthma , anaphylaxis or anaphylactoid reactions, severe allergic responses

• Abuse of alcohol or drugs within the last 6 months

• Any factor or clinical disease state that, in the investigator's opinion, would preclude completion of a safe surgical procedure and/or completion of the study

• Use of an investigational drugs within 30 days or 5 half-lives of their last dose prior to starting the study, whichever is the longest