A Randomized, Double-Blind, Double-Dummy, Active-Controlled Study to Evaluate the Efficacy and Safety of REGN727/SAR236553 in Patients With Primary Hypercholesterolemia Who Are Intolerant to Statins
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 314
- 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
This is a randomized, double-blind, double-dummy, active-controlled, parallel-group, multi-national, multi-center study to compare alirocumab (REGN727/SAR236553) versus ezetimibe in participants with primary hypercholesterolemia and moderate, high, or very high CV risk, who are intolerant to statins. An atorvastatin arm is added to determine that the population selected in the study is a truly statin intolerant population by assessing skeletal muscle-related adverse events.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Ezetimibe
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
干预措施: Ezetimibe (Drug)
Ezetimibe
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
干预措施: Placebo (Drug)
Atorvastatin (statin rechallenge arm)
Atorvastatin 20 mg over-encapsulated tablets orally once daily (QD) for 24 weeks and placebo (for alirocumab) subcutaneous (SC) injection every two weeks (Q2W) for 24 weeks added to stable lipid-modifying therapy (LMT).
干预措施: Atorvastatin (Drug)
Atorvastatin (statin rechallenge arm)
Atorvastatin 20 mg over-encapsulated tablets orally once daily (QD) for 24 weeks and placebo (for alirocumab) subcutaneous (SC) injection every two weeks (Q2W) for 24 weeks added to stable lipid-modifying therapy (LMT).
干预措施: Placebo (Drug)
Alirocumab 75 mg/ up to 150 mg
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
干预措施: Alirocumab (Drug)
Alirocumab 75 mg/ up to 150 mg
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
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 Total Cholesterol (Total--C) at Week 24 - ITT Analysis(From Baseline to Week 24)
- Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or Moderate 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)
- Percent Change From Baseline in Calculated LDL-C at Week 12 - On--Treatment Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Non--HDL-C at Week 24 -- On--Treatment Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Apo B 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 Moderate 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)
- Percent Change From Baseline in Apo A--1 at Week 12 -- ITT Analysis(From Baseline to Week 12)
- 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 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 Apolipoprotein (Apo) B at Week 24 -- ITT Analysis(From Baseline to Week 24)
- 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 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 Lipoprotein(a) at Week 24 - ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in HDL-C 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 in HDL-C From Baseline to Week 12 -- ITT Analysis(From Baseline to Week 12)
- 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 in Fasting Triglycerides From Baseline to Week 12 -- ITT Analysis(From Baseline to Week 12)