Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Ezetimibe in Patients With Hypercholesterolemia
- Conditions
- Hypercholesterolemia
- Interventions
- Registration Number
- NCT01644474
- Lead Sponsor
- Sanofi
- Brief Summary
Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9).
Primary Objective of the study:
To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab in comparison with ezetimibe after 24 weeks of treatment in participants with hypercholesterolemia.
Secondary Objectives:
* To evaluate the effect of alirocumab in comparison with ezetimibe on LDL-C at other time points
* To evaluate the effect of alirocumab on other lipid parameters
* To evaluate the safety and tolerability of alirocumab
- Detailed Description
The maximum study duration was 34 weeks per participant, including a 24-week randomized treatment period.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 103
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ezetimibe 10 mg Placebo (for Alirocumab) Oral ezetimibe 10 mg capsule daily and subcutaneous (SC) placebo injection for alirocumab every 2 weeks (Q2W) for 24 weeks. Alirocumab 75/Up to 150 mg Q2W Placebo (for Ezetimibe) SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8. Ezetimibe 10 mg Ezetimibe Oral ezetimibe 10 mg capsule daily and subcutaneous (SC) placebo injection for alirocumab every 2 weeks (Q2W) for 24 weeks. Alirocumab 75/Up to 150 mg Q2W Alirocumab SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
- Primary Outcome Measures
Name Time Method Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis 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).
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis From Baseline to Week 24 Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis Up to Week 24 Adjusted percentages at Week 24 from multiple imputation approach model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Apo B at Week 12 - ITT Analysis From Baseline to Week 24 Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Total-C at Week 12 - ITT Analysis From Baseline to Week 24 Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis From Baseline to Week 24 Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis From Baseline to Week 24 Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis From Baseline to Week 24 Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24 - ITT Analysis From Baseline to Week 24 Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis From Baseline to Week 24 Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis Up to Week 24 Adjusted percentages at Week 24 were obtained from multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model.
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis From Baseline to Week 24 Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis From Baseline to Week 24 Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis From Baseline to Week 24 Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis From Baseline to Week 24 Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis From Baseline to Week 24 Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis From Baseline to Week 24 Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24 - ITT Analysis From Baseline to Week 24 Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Trial Locations
- Locations (8)
Investigational Site Number 840603
🇺🇸Overland Park, Kansas, United States
Investigational Site Number 840601
🇺🇸Cincinnati, Ohio, United States
Investigational Site Number 528602
🇳🇱Groningen, Netherlands
Investigational Site Number 246601
🇫🇮Helsinki, Finland
Investigational Site Number 528603
🇳🇱Velp, Netherlands
Investigational Site Number 056601
🇧🇪Antwerpen, Belgium
Investigational Site Number 840602
🇺🇸Richmond, Virginia, United States
Investigational Site Number 528601
🇳🇱Rotterdam, Netherlands