A Double-Blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Long-Term Tolerability and Durable Efficacy of AMG 145 (Evolocumab) on LDL-C in Hyperlipidemic Subjects
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 905
- 试验地点
- 1
- 主要终点
- Percent Change From Baseline in LDL-C at Week 52
研究概览
简要总结
To evaluate the efficacy, safety, and tolerability of 52 weeks of subcutaneous (SC) evolocumab (AMG 145) compared with placebo when added to assigned background lipid-lowering therapy.
详细描述
Eligible participants with screening central laboratory low-density lipoprotein cholesterol (LDL-C) values ≥ 75 mg/dL (1.9 mmol/L) were instructed to follow National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP) Therapeutic Lifestyle Changes (TLC) diet and were assigned to 1 of the following 4 background lipid-lowering therapies for a 4-week stabilization period based upon their screening LDL-C and its distance from the individual's required goal as stipulated by their NCEP ATP III risk category:
- no drug therapy required - diet alone
- low dose drug therapy required - diet plus atorvastatin 10 mg orally (PO) once daily (QD)
- high dose drug therapy required - diet plus atorvastatin 80 mg PO QD
- maximal drug therapy required - diet plus atorvastatin 80 mg PO QD plus ezetimibe 10 mg PO QD.
If the participant met entry criteria at the end of the lipid stabilization period they were randomized 2:1 to receive evolocumab 420 mg or placebo subcutaneously once a month for 52 weeks in addition to their background therapy.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject has provided informed consent.
- •Fasting LDL-C ≥ 75 mg/dL and meeting the following LDL-C values on background lipid-lowering therapy:
- •< 100 mg/dL for subjects with diagnosed coronary heart disease (CHD) or CHD risk equivalent
- •< 130 mg/dL for subjects without diagnosed CHD or CHD risk equivalent
- •OR on maximal background lipid-lowering therapy defined as atorvastatin 80 mg PO QD and ezetimibe 10 mg PO QD
- •Fasting triglycerides ≤ 400 mg/dL
排除标准
- •New York Heart Association (NYHA) II-IV heart failure, or last known left ventricular ejection fraction < 30%
- •Uncontrolled cardiac arrhythmia
- •Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to randomization, type 1 diabetes, newly diagnosed or poorly controlled type 2 diabetes
- •Uncontrolled hypertension
研究组 & 干预措施
Placebo
Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
干预措施: Ezetimibe (Drug)
Placebo
Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
干预措施: Diet Only (Other)
Evolocumab
Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
干预措施: Evolocumab (Biological)
Evolocumab
Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
干预措施: Atorvastatin (Drug)
Evolocumab
Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
干预措施: Ezetimibe (Drug)
Evolocumab
Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
干预措施: Diet Only (Other)
Placebo
Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
干预措施: Placebo (Biological)
Placebo
Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
干预措施: Atorvastatin (Drug)
结局指标
主要结局
Percent Change From Baseline in LDL-C at Week 52
时间窗: Baseline and Week 52
Cholesterol was measured by means of ultracentrifugation.
次要结局
- Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 52(Baseline and Week 52)
- Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 52(Baseline and Week 52)
- Percent Change From Baseline in Lipoprotein(a) at Week 52(Baseline and Week 52)
- Percent Change From Baseline in Triglycerides at Week 52(Baseline and Week 52)
- Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 52(Baseline and Week 52)
- Change From Baseline in LDL-C at Week 52(Baseline and Week 52)
- Percentage of Participants With an LDL-C Response at Week 52(Week 52)
- Percent Change From Baseline in LDL-C at Week 12(Baseline and Week 12)
- Percent Change From Baseline in Total Cholesterol at Week 12(Baseline and Week 12)
- Percent Change From Baseline in Total Cholesterol at Week 52(Baseline and Week 52)
- Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at Week 52(Baseline and Week 52)
- Percent Change From Baseline in Apolipoprotein B at Week 52(Baseline and Week 52)
- Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at Week 52(Baseline and Week 52)
- Percent Change From Week 12 to Week 52 in LDL-C(Week 12 and Week 52)