A Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicenter Study Evaluating the Efficacy and Safety of Five Doses and Two Dose Regimens of SAR236553 Over 12 Weeks in Patients With Primary Hypercholesterolemia and LDL-cholesterol ≥ 100 mg/dL (≥ 2.59 mmol/L) on Ongoing Stable Atorvastatin Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 183
- 试验地点
- 38
- 主要终点
- Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
研究概览
简要总结
Primary Objective:
- To evaluate the effect of alirocumab (SAR236553/REGN727) on low-density lipoprotein cholesterol (LDL-C) levels after 12 weeks of treatment in comparison with placebo in participants with LDL-C ≥ 100 mg/dL (≥ 2.59 mmol/L) on ongoing stable atorvastatin therapy.
Secondary Objectives:
- To evaluate the effects of alirocumab on other lipid levels after 12 weeks of treatment in comparison with placebo
- To evaluate the safety and tolerability of alirocumab
- To evaluate the development of anti-alirocumab antibodies
- To evaluate the pharmacokinetics of alirocumab
详细描述
The duration of study participation depended on the status of the participant at screening:
- For participants receiving atorvastatin 10 mg, 20 mg, or 40 mg at a stable dose for at least 6 weeks prior to screening, the study participation was to be approximately 21 weeks including a screening period of 1 week, a double-blind treatment period of 12 weeks and a follow-up period of 8 weeks.
- For participants receiving a lipid-lowering treatment other than atorvastatin or not at stable dose of atorvastatin 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to screening, or drug naive participants, the study participation was to be approximately 27 weeks including a screening period of 1 week, a run-in treatment period with atorvastatin 10 mg, 20 mg, or 40 mg at a stable dose of 6 weeks, a double-blind treatment period of 12 weeks, and a follow-up period of 8 weeks.
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 75 Years（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
Placebo Q2W
Placebo (for alirocumab) every 2 weeks (Q2W) for 12-weeks in combination with atorvastatin stable dose.
干预措施: Placebo (for alirocumab) (Drug)
Placebo Q2W
Placebo (for alirocumab) every 2 weeks (Q2W) for 12-weeks in combination with atorvastatin stable dose.
干预措施: Atorvastatin (Drug)
Alirocumab 50 mg Q2W
Alirocumab 50 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
干预措施: Alirocumab (Drug)
Alirocumab 50 mg Q2W
Alirocumab 50 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
干预措施: Atorvastatin (Drug)
Alirocumab 100 mg Q2W
Alirocumab 100 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
干预措施: Alirocumab (Drug)
Alirocumab 100 mg Q2W
Alirocumab 100 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
干预措施: Atorvastatin (Drug)
Alirocumab 150 mg Q2W
Alirocumab 150 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
干预措施: Alirocumab (Drug)
Alirocumab 150 mg Q2W
Alirocumab 150 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
干预措施: Atorvastatin (Drug)
Alirocumab 200 mg Q4W
Alirocumab 200 mg every 4 weeks (Q4W) and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose.
干预措施: Alirocumab (Drug)
Alirocumab 200 mg Q4W
Alirocumab 200 mg every 4 weeks (Q4W) and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose.
干预措施: Placebo (for alirocumab) (Drug)
Alirocumab 200 mg Q4W
Alirocumab 200 mg every 4 weeks (Q4W) and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose.
干预措施: Atorvastatin (Drug)
Alirocumab 300 mg Q4W
Alirocumab 300 mg Q4W and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose.
干预措施: Alirocumab (Drug)
Alirocumab 300 mg Q4W
Alirocumab 300 mg Q4W and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose.
干预措施: Placebo (for alirocumab) (Drug)
Alirocumab 300 mg Q4W
Alirocumab 300 mg Q4W and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose.
干预措施: Atorvastatin (Drug)
结局指标
主要结局
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
时间窗: Baseline to Week 12 (LOCF)
Calculated LDL-C values were obtained using the Friedewald formula. Baseline adjusted least squares (LS) means and standard errors were estimated using an analysis of covariance (ANCOVA) model including available post-baseline data on treatment from first study drug injection up to 21 days after last study drug injection (on-treatment analysis). Missing Week 12 data were imputed by last observation carried forward \[LOCF\] method.
次要结局
- Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 12 - On-Treatment Analysis(Baseline to Week 12 (LOCF))
- Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 12 - On-Treatment Analysis(Baseline to Week 12 (LOCF))
- Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and <70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis(Week 12 (LOCF))
- Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis(Baseline to Week 12 (LOCF))
- Percent Change From Baseline in Fasting Triglycerides and Lipoprotein(a) at Week 12 - On-Treatment Analysis(Baseline to Week 12 (LOCF))
- Absolute Change in the Ratio Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) From Baseline to Week 12 - On-Treatment Analysis(Baseline to Week 12 (LOCF))