A Randomized, Double-Blind Study of the Efficacy and Safety of REGN727 Added-on to Rosuvastatin Versus Ezetimibe Added-on to Rosuvastatin Versus Rosuvastatin Dose Increase in Patients Who Are Not Controlled on Rosuvastatin
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 305
- 试验地点
- 2
- 主要终点
- Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis
研究概览
简要总结
To evaluate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab (REGN727/SAR236553) as an add-on therapy to other LMT in patients with hypercholesterolemia at high cardiovascular (CV) risk.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with LDL-C greater than or equal to 70 mg/dL at the screening visit and who are not adequately controlled with a stable daily dose of rosuvastatin, with or without other LMT.
- •Patients with screening LDL-C greater than or equal to 100 mg/dL who are not adequately controlled with a stable daily dose of rosuvastatin before the screening visit, with or without other LMT.
排除标准
- •LDL-C less than 70 mg/dL at the screening visit in patients with history of documented cardiovascular disease (CVD)
- •LDL-C less than 100 mg/dL at the screening visit in patients without history of documented coronary heart disease (CHD) or non-CHD CVD, but with other risk factors
- •Homozygous familial hypercholesterolemia (FH) (clinically or previous genotyping)
- •Recent (within 3 months prior to the screening visit) myocardial infarction (MI), unstable angina leading to hospitalization, percutaneous coronary intervention (PCI), coronary bypass graft surgery (CABG), uncontrolled cardiac arrhythmia, stroke, transient ischemic attack, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease
- •Newly diagnosed (within 3 months prior to randomization visit) or poorly controlled diabetes
- •Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins
- •(The inclusion/ exclusion criteria provided above is not intended to contain all considerations relevant to a patient's potential participation in this clinical trial).
研究组 & 干预措施
Rosuvastatin 20 mg
Participants, who were receiving rosuvastatin 10 mg over-encapsulated tablet orally at baseline, received rosuvastatin 20 mg over-encapsulated tablet orally once daily (QD), placebo for alirocumab SC injection every two weeks (Q2W), and placebo for ezetimibe over-encapsulated tablet orally QD added to stable Lipid-Modifying Therapy (LMT) for 24 weeks.
干预措施: Rosuvastatin (Drug)
Rosuvastatin 20 mg
Participants, who were receiving rosuvastatin 10 mg over-encapsulated tablet orally at baseline, received rosuvastatin 20 mg over-encapsulated tablet orally once daily (QD), placebo for alirocumab SC injection every two weeks (Q2W), and placebo for ezetimibe over-encapsulated tablet orally QD added to stable Lipid-Modifying Therapy (LMT) for 24 weeks.
干预措施: Placebo (Drug)
Ezetimibe 10 mg + Rosuvastatin 10 mg
Participants, who were receiving rosuvastatin 10 mg over-encapsulated tablet orally at baseline, received ezetimibe 10 mg over-encapsulated tablet orally QD, rosuvastatin 10 mg over-encapsulated tablet orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks.
干预措施: Rosuvastatin (Drug)
Ezetimibe 10 mg + Rosuvastatin 10 mg
Participants, who were receiving rosuvastatin 10 mg over-encapsulated tablet orally at baseline, received ezetimibe 10 mg over-encapsulated tablet orally QD, rosuvastatin 10 mg over-encapsulated tablet orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks.
干预措施: Ezetimibe (Drug)
Ezetimibe 10 mg + Rosuvastatin 10 mg
Participants, who were receiving rosuvastatin 10 mg over-encapsulated tablet orally at baseline, received ezetimibe 10 mg over-encapsulated tablet orally QD, rosuvastatin 10 mg over-encapsulated tablet orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks.
干预措施: Placebo (Drug)
Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Participants, who were receiving rosuvastatin 10 mg over-encapsulated tablet orally at baseline, received alirocumab 75 mg SC injection Q2W, rosuvastatin 10 mg over-encapsulated tablet orally QD, and placebo for ezetimibe over-encapsulated tablet orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
干预措施: Alirocumab (Drug)
Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Participants, who were receiving rosuvastatin 10 mg over-encapsulated tablet orally at baseline, received alirocumab 75 mg SC injection Q2W, rosuvastatin 10 mg over-encapsulated tablet orally QD, and placebo for ezetimibe over-encapsulated tablet orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
干预措施: Rosuvastatin (Drug)
Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Participants, who were receiving rosuvastatin 10 mg over-encapsulated tablet orally at baseline, received alirocumab 75 mg SC injection Q2W, rosuvastatin 10 mg over-encapsulated tablet orally QD, and placebo for ezetimibe over-encapsulated tablet orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
干预措施: Placebo (Drug)
Rosuvastatin 40 mg
Participants, who were receiving rosuvastatin 20 mg over-encapsulated tablet orally at baseline, received rosuvastatin 40 mg over-encapsulated tablet orally QD, placebo for alirocumab Q2W SC injection, and placebo for ezetimibe QD over-encapsulated tablet orally added to stable LMT for 24 weeks.
干预措施: Rosuvastatin (Drug)
Rosuvastatin 40 mg
Participants, who were receiving rosuvastatin 20 mg over-encapsulated tablet orally at baseline, received rosuvastatin 40 mg over-encapsulated tablet orally QD, placebo for alirocumab Q2W SC injection, and placebo for ezetimibe QD over-encapsulated tablet orally added to stable LMT for 24 weeks.
干预措施: Placebo (Drug)
Ezetimibe 10 mg + Rosuvastatin 20 mg
Participants, who were receiving rosuvastatin 20 mg over-encapsulated tablet orally at baseline, received ezetimibe 10 mg over-encapsulated tablet orally QD, rosuvastatin 20 mg over-encapsulated tablet orally QD, and placebo for alirocumab Q2W SC injection added to stable LMT for 24 weeks.
干预措施: Rosuvastatin (Drug)
Ezetimibe 10 mg + Rosuvastatin 20 mg
Participants, who were receiving rosuvastatin 20 mg over-encapsulated tablet orally at baseline, received ezetimibe 10 mg over-encapsulated tablet orally QD, rosuvastatin 20 mg over-encapsulated tablet orally QD, and placebo for alirocumab Q2W SC injection added to stable LMT for 24 weeks.
干预措施: Ezetimibe (Drug)
Ezetimibe 10 mg + Rosuvastatin 20 mg
Participants, who were receiving rosuvastatin 20 mg over-encapsulated tablet orally at baseline, received ezetimibe 10 mg over-encapsulated tablet orally QD, rosuvastatin 20 mg over-encapsulated tablet orally QD, and placebo for alirocumab Q2W SC injection added to stable LMT for 24 weeks.
干预措施: Placebo (Drug)
Alirocumab 75 mg/ up to 150 mg + Rosuvastatin 20 mg
Participants, who were receiving rosuvastatin 20 mg over-encapsulated tablet orally at baseline, received alirocumab 75 mg Q2W SC injection, rosuvastatin 20 mg over-encapsulated tablet orally QD, and placebo for ezetimibe over-encapsulated tablet orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
干预措施: Alirocumab (Drug)
Alirocumab 75 mg/ up to 150 mg + Rosuvastatin 20 mg
Participants, who were receiving rosuvastatin 20 mg over-encapsulated tablet orally at baseline, received alirocumab 75 mg Q2W SC injection, rosuvastatin 20 mg over-encapsulated tablet orally QD, and placebo for ezetimibe over-encapsulated tablet orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
干预措施: Rosuvastatin (Drug)
Alirocumab 75 mg/ up to 150 mg + Rosuvastatin 20 mg
Participants, who were receiving rosuvastatin 20 mg over-encapsulated tablet orally at baseline, received alirocumab 75 mg Q2W SC injection, rosuvastatin 20 mg over-encapsulated tablet orally QD, and placebo for ezetimibe over-encapsulated tablet orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
干预措施: Placebo (Drug)
结局指标
主要结局
Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis
时间窗: From Baseline to Week 24
Calculated LDL-C values were obtained from Friedewald formula. Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).
次要结局
- Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Apo B at Week 12 - ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Total-C at Week 12 - ITT Analysis(From Baseline to Week 12)
- Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis(Up to Week 24)
- Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis(Up to Week 24)
- Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis(Up to Week 24)
- Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis(Up to Week 24)
- Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis(From Baseline to Week 24)