A Multi-centre, Randomised, Double-blind, Placebo-controlled, Parallel-group Study to Investigate the Effect of the Lp-PLA2 Inhibitor SB-480848 (40, 80mg od) on Carotid Plaque Composition in Patients With Carotid Artery Disease and Planned Carotid Endarterectomy, Stratified for Statin Use and Gender, After 14+/-4 Days Treatment
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 103
- 主要终点
- Lp-PLA2 activity in the atherosclerotic plaque removed during carotid endarterectomy
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 35 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
SB-480848 40 mg
SB-480848 40 milligrams (mg) once a day (od) for 14 +/- 4 days followed by carotid endarterectomy. SB-480848 40 mg was administered as 2 SB-480848 20 mg tablets plus 2 placebo tablets.
干预措施: SB-480848 40 mg (Drug)
SB-480848 40 mg
SB-480848 40 milligrams (mg) once a day (od) for 14 +/- 4 days followed by carotid endarterectomy. SB-480848 40 mg was administered as 2 SB-480848 20 mg tablets plus 2 placebo tablets.
干预措施: Placebo (Drug)
SB-480848 80 mg
SB-480848 80 mg od for 14 +/- 4 days followed by carotid endarterectomy.SB-480848 80 mg was administered as 4 20 mg SB-480848 tablets.
干预措施: SB-480848 80 mg (Drug)
Matching Placebo
Placebo for 14 +/- 4 days followed by carotid endarterectomy. Placebo was administered as 4 placebo tablets. Placebo tablets were identical in appearance to the SB-480848 20 mg tablets.
干预措施: Placebo (Drug)
结局指标
主要结局
Lp-PLA2 activity in the atherosclerotic plaque removed during carotid endarterectomy
时间窗: 14 +/- 4 days
次要结局
- Lp-PLA2 mass and activity in blood(14 +/- days)
- Lp-PLA2 mass in plaque removed during the carotid endarterectomy(14 +/- 4 days)
- Lipid and Non-Lipid Biomarkers in Plasma(14 +/- days)
- Oxidised Lipids and Their Metabolites, and Biomarkers in Plaque(14 +/- 4 days)