A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Alirocumab in Insulin Treated Patients With Type 1 or Type 2 Diabetes and With Hypercholesterolemia at High Cardiovascular Risk Not Adequately Controlled on Maximally Tolerated LDL-C Lowering Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 517
- 试验地点
- 110
- 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
Primary Objectives:
- To demonstrate the superiority of alirocumab in comparison with placebo in the reduction of calculated low-density lipoprotein cholesterol (LDL-C) in participants with diabetes treated with insulin and with hypercholesterolemia at high cardiovascular risk not adequately controlled on maximally tolerated LDL-C lowering therapy.
- To evaluate the safety and tolerability of alirocumab in participants with diabetes treated with insulin.
Secondary Objective:
To demonstrate that alirocumab was superior in comparison to placebo in its effects on other lipid parameters (i.e., measured LDL-C, non-high-density lipoprotein cholesterol [non-HDL-C], apolipoprotein B [Apo B], total cholesterol [TC], lipoprotein a [Lp(a)], high density lipoprotein cholesterol [HDL-C], triglyceride [TG] levels, triglyceride rich lipoproteins [TGRL], apolipoprotein A-1 [Apo A-1], apolipoprotein C-III [Apo C-III], and LDL particle number and size).
详细描述
The maximum study duration was approximately 9 months per participant, including a 6 month treatment period, a screening period of up to 3 weeks, and an 8 week safety observation period.
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
- Double (Participant, Investigator)
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
Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Alirocumab 75 mg subcutaneous (SC) injection every 2 weeks (Q2W) added to stable, maximally tolerated dose of statin therapy with or without other lipid-modifying therapy (LMT), insulin alone or with other antihyperglycemic drugs 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) at Week 8.
干预措施: Alirocumab (Drug)
Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Alirocumab 75 mg subcutaneous (SC) injection every 2 weeks (Q2W) added to stable, maximally tolerated dose of statin therapy with or without other lipid-modifying therapy (LMT), insulin alone or with other antihyperglycemic drugs 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) at Week 8.
干预措施: Lipid-Modifying Therapy (LMT) (Drug)
Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Alirocumab 75 mg subcutaneous (SC) injection every 2 weeks (Q2W) added to stable, maximally tolerated dose of statin therapy with or without other lipid-modifying therapy (LMT), insulin alone or with other antihyperglycemic drugs 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) at Week 8.
干预措施: Antihyperglycemic Drug (Drug)
Placebo Q2W
Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
干预措施: Placebo (Drug)
Placebo Q2W
Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
干预措施: Lipid-Modifying Therapy (LMT) (Drug)
Placebo Q2W
Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
干预措施: Antihyperglycemic Drug (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
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).
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs)
时间窗: From Baseline up to 10 weeks after last study drug administration (maximum of 32 weeks)
Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
次要结局
- Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis(Up to Week 24)
- Percentage of Participants Reaching Calculated Non-HDL-C <100 mg/dL at Week 24 - On-Treatment Analysis(Up to Week 24)
- Absolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - On-Treatment Analysis(Baseline, Weeks 12 and 24)
- Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT 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 HDL-C at Week 24 - ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Measured LDL-C at Week 12 - ITT Analysis(From Baseline 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 Fasting Triglycerides at Week 24 - ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis(From Baseline to Week 24)
- Percentage of Participants Reaching Calculated Non-HDL-C <80 mg/dL at Week 24 - On-Treatment Analysis(Up to Week 24)
- Percent Change From Baseline in Apolipoprotein B (Apo-B) at Week 24 - ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Measured LDL-C at Week 24 - ITT 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)
- Percentage of Participants Reaching Calculated LDL-C <50 mg/dL (1.3 mmol/L) at Week 24 - On-Treatment Analysis(Up to Week 24)
- Percent Change From Baseline in LDL-C Particle Number at Week 24 - ITT Analysis(From Baseline to Week 24)
- Absolute Change From Baseline in HbA1c at Weeks 12 and 24 - On-Treatment Analysis(Baseline, Weeks 12 and 24)
- Percent Change From Baseline in LDL-C Particle Size at Week 24 - ITT Analysis(From Baseline to Week 24)
- Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Weeks 12 and 24 - ITT Analysis(Baseline, Weeks 12 and 24)
- Absolute Change From Baseline in FPG at Weeks 12 and 24 - On-Treatment Analysis(Baseline, Weeks 12 and 24)
- Absolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - ITT Analysis(Baseline, Weeks 12 and 24)
- Absolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - On-Treatment Analysis(Baseline, Weeks 12 and 24)
- Absolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - ITT Analysis(Baseline, Weeks 12 and 24)
- Absolute Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 12 and 24 - ITT Analysis(Baseline, Weeks 12 and 24)
- Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - ITT Analysis(Baseline, Weeks 12 and 24)
- Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - On-Treatment Analysis(Baseline, Weeks 12 and 24)