A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Safety, Tolerability and Efficacy of Evolocumab (AMG 145) on LDL-C in Combination With Statin Therapy in Japanese Subjects With High Cardiovascular Risk and With Hyperlipidemia or Mixed Dyslipidemia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 409
- 试验地点
- 1
- 主要终点
- Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
研究概览
简要总结
The primary objective of the study was to evaluate the effect of 12 weeks of subcutaneous evolocumab administered every 2 weeks and once a month, compared with placebo, on percent change from baseline in LDL-C when used in combination with statin therapy in adults with high cardiovascular risk and with hyperlipidemia or mixed dyslipidemia.
详细描述
After a screening and placebo run-in period, eligible patients were randomized in a 1:1 ratio to 1 of 2 open-label background statin treatments (atorvastatin 5 mg or 20 mg daily [QD]) and entered a 4-week lipid stabilization period. After the lipid stabilization period, eligible patients were randomized in a 1:1:1:1 ratio to investigational product (evolocumab or placebo) for the 12-week treatment period.
Both randomizations were stratified by subject diagnosis and lipid-lowering therapy as follows:
- current or prior diagnosis of heterozygous familial hypercholesterolemia (HeFH)
- no diagnosis of HeFH and receiving intensive lipid-lowering therapy
- no diagnosis of HeFH and receiving non-intensive lipid-lowering therapy. A participant was considered randomized into the study after successfully completing the screening period, meeting all inclusion/exclusion criteria including meeting final laboratory safety criteria, and undergoing both randomization procedures.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 20 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, Japanese adult, 20-85 years of age; Subjects on stable dose of statin for greater than equal to 4 weeks; Fasting LDL-C greater than equal to 100 mg/dL; Fasting triglycerides less than equal to 400 mg/dL; Subject is at high risk for cardiovascular events.
排除标准
- •New York heart Association (NYHA) III or IV - heart failure; Uncontrolled cardiac arrhythmia; Uncontrolled hypertension; Type 1 diabetes, poorly controlled type 2 diabetes; Uncontrolled hypothyroidism or hyperthyroidism
研究组 & 干预措施
A5 Placebo Q2W
Participants received atorvastatin 5 mg (A5) once daily during the 4 week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks.
干预措施: Atorvastatin (Drug)
A5 Placebo Q2W
Participants received atorvastatin 5 mg (A5) once daily during the 4 week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks.
干预措施: Placebo to Evolocumab (Other)
A5 Placebo QM
Participants received atorvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month (QM) for 12 weeks.
干预措施: Atorvastatin (Drug)
A5 Placebo QM
Participants received atorvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month (QM) for 12 weeks.
干预措施: Placebo to Evolocumab (Other)
A5 Evolocumab Q2W
Participants received atorvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
干预措施: Atorvastatin (Drug)
A5 Evolocumab Q2W
Participants received atorvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
干预措施: Evolocumab (Biological)
A5 Evolocumab QM
Participants received atorvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for 12 weeks.
干预措施: Atorvastatin (Drug)
A5 Evolocumab QM
Participants received atorvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for 12 weeks.
干预措施: Evolocumab (Biological)
A20 Placebo Q2W
Participants received atorvastatin 20 mg (A20) once daily during the 4 week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for 12 weeks.
干预措施: Atorvastatin (Drug)
A20 Placebo Q2W
Participants received atorvastatin 20 mg (A20) once daily during the 4 week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for 12 weeks.
干预措施: Placebo to Evolocumab (Other)
A20 Placebo QM
Participants received atorvastatin 20 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month for 12 weeks.
干预措施: Atorvastatin (Drug)
A20 Placebo QM
Participants received atorvastatin 20 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month for 12 weeks.
干预措施: Placebo to Evolocumab (Other)
A20 Evolocumab Q2W
Participants received atorvastatin 20 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
干预措施: Atorvastatin (Drug)
A20 Evolocumab Q2W
Participants received atorvastatin 20 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
干预措施: Evolocumab (Biological)
A20 Evolocumab QM
Participants received atorvastatin 20 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for 12 weeks.
干预措施: Atorvastatin (Drug)
A20 Evolocumab QM
Participants received atorvastatin 20 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for 12 weeks.
干预措施: Evolocumab (Biological)
结局指标
主要结局
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
时间窗: Baseline and Week 12
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at the Mean of Weeks 10 and 12
时间窗: Baseline and Weeks 10 and 12
次要结局
- Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12(Baseline and Weeks 10 and 12)
- Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12(Week 12)
- Change From Baseline in LDL-C at the Mean of Weeks 10 and 12(Baseline and Weeks 10 and 12)
- Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12(Baseline and Weeks 10 and 12)
- Percent Change From Baseline in Apolipoprotein B 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 the Total Cholesterol/HDL-C Ratio at Week 12(Baseline and Week 12)
- Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at the Mean of Weeks 10 and 12(Baseline and Weeks 10 and 12)
- Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12(Baseline and Weeks 10 and 12)
- Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL(Weeks 10 and 12)
- Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12(Baseline and Weeks 10 and 12)
- Percent Change From Baseline in VLDL-C at Week 12(Baseline and Week 12)
- Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12(Baseline and Weeks 10 and 12)
- Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12(Baseline and Weeks 10 and 12)
- Percent Change From Baseline in HDL-C at Week 12(Baseline and Week 12)
- Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12(Baseline and Weeks 10 and 12)
- Change From Baseline in LDL-C at Week 12(Baseline and Week 12)
- Percent Change From Baseline in Non-HDL-C at Week 12(Baseline and Week 12)
- Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12(Baseline and Weeks 10 and 12)
- Percent Change From Baseline in the Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12(Baseline and Week 12)
- Percent Change From Baseline in Lipoprotein(a) at Week 12(Baseline and Week 12)
- Percent Change From Baseline in Triglycerides at Week 12(Baseline and Week 12)