Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Ezetimibe on Top of Statin in High Cardiovascular Risk Patients With Hypercholesterolemia (ODYSSEY COMBO II)
- Conditions
- Hypercholesterolemia
- Interventions
- Drug: Placebo (for alirocumab)Drug: AlirocumabDrug: Placebo (for ezetimibe)Drug: EzetimibeDrug: Lipid Modifying Therapy (LMT)
- Registration Number
- NCT01644188
- 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 as add-on therapy to stable maximally tolerated daily statin therapy in comparison with ezetimibe after 24 weeks of treatment in participants with hypercholesterolemia at high cardiovascular (CV) risk.
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 115 weeks per participant, including a 3-week screening period, 104-week randomized treatment period and 8-week follow-up period.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 720
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Alirocumab 75 /up to 150 mg Q2W Placebo (for ezetimibe) Alirocumab 75 mg every 2 weeks (Q2W) and oral placebo capsule for ezetimibe daily added to stable Lipid Modifying Therapy (LMT) for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8. Alirocumab 75 /up to 150 mg Q2W Lipid Modifying Therapy (LMT) Alirocumab 75 mg every 2 weeks (Q2W) and oral placebo capsule for ezetimibe daily added to stable Lipid Modifying Therapy (LMT) for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8. Ezetimibe 10 mg Placebo (for alirocumab) Ezetimibe 10 mg capsule daily and subcutaneous placebo for alirocumab Q2W added to stable LMT for 104 weeks. Ezetimibe 10 mg Lipid Modifying Therapy (LMT) Ezetimibe 10 mg capsule daily and subcutaneous placebo for alirocumab Q2W added to stable LMT for 104 weeks. Alirocumab 75 /up to 150 mg Q2W Alirocumab Alirocumab 75 mg every 2 weeks (Q2W) and oral placebo capsule for ezetimibe daily added to stable Lipid Modifying Therapy (LMT) for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8. Ezetimibe 10 mg Ezetimibe Ezetimibe 10 mg capsule daily and subcutaneous placebo for alirocumab Q2W added to stable LMT for 104 weeks.
- 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 52 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 52 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 52 Adjusted LS means and standard errors at Week 12 from a MMRM including all available post-baseline data from week 4 to week 52 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 52 Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first).
Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis From Baseline to Week 52 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 52 regardless of status on- or off-treatment.
Percent Change From Baseline in Calculated LDL--C at Week 24 - On--Treatment Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first).
Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first).
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis From Baseline up to Week 52 Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first).
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Percent Change From Baseline in Apo-B at Week 12 - ITT Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 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 52 Adjusted percentages at Week 24 were obtained from multiple imputation approach for handling of missing data. All available post-baseline data from week 4 to week 52 regardless of status on- or off-treatment were included in the imputation model.
Percent Change From Baseline in Total-C at Week 12 - ITT Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 52 from a MMRM model including all available post-baseline data from week 4 to week 52 regardless of status on- or off-treatment.
Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis Up to Week 52 Adjusted percentages at Week 24 from multiple imputation approach including available post-baseline on-treatment data from week 4 to week 52 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first).
Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis From baseline to Week 52 Adjusted means and standard errors at Week 24 were obtained from multiple imputation approach followed by robust regression model for handling of missing data. All available post-baseline data from Week 4 to Week 52 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 52 Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 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 52 Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Percent Change From Baseline in Lipoprotein(a) at Week 12 - ITT Analysis From Baseline to Week 52 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 52 regardless of status on- or off-treatment.
Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis From Baseline to Week 52 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 52 regardless of status on- or off-treatment.
Trial Locations
- Locations (126)
Investigational Site Number 840979
🇺🇸Los Angeles, California, United States
Investigational Site Number 840966
🇺🇸Fall River, Massachusetts, United States
Investigational Site Number 840946
🇺🇸Butte, Montana, United States
Investigational Site Number 840914
🇺🇸Lincoln, Nebraska, United States
Investigational Site Number 840955
🇺🇸Greenville, North Carolina, United States
Investigational Site Number 124903
🇨🇦Montreal, Canada
Investigational Site Number 840952
🇺🇸Palm Springs, California, United States
Investigational Site Number 840301
🇺🇸Beverly Hills, California, United States
Investigational Site Number 840932
🇺🇸Bristol, Tennessee, United States
Investigational Site Number 840945
🇺🇸Sugar Land, Texas, United States
Investigational Site Number 348905
🇭🇺Debrecen, Hungary
Investigational Site Number 840931
🇺🇸Norfolk, Virginia, United States
Investigational Site Number 840997
🇺🇸Marion, Ohio, United States
Investigational Site Number 840992
🇺🇸Summerville, South Carolina, United States
Investigational Site Number 348908
🇭🇺Budapest, Hungary
Investigational Site Number 376906
🇮🇱Ofakim, Israel
Investigational Site Number 376908
🇮🇱Holon, Israel
Investigational Site Number 124902
🇨🇦Brampton, Canada
Investigational Site Number 208901
🇩🇰København S, Denmark
Investigational Site Number 840928
🇺🇸Renton, Washington, United States
Investigational Site Number 840959
🇺🇸Anaheim, California, United States
Investigational Site Number 840982
🇺🇸Orem, Utah, United States
Investigational Site Number 840971
🇺🇸Tomball, Texas, United States
Investigational Site Number 840303
🇺🇸Sarasota, Florida, United States
Investigational Site Number 840912
🇺🇸Greer, South Carolina, United States
Investigational Site Number 124914
🇨🇦Mirabel, Canada
Investigational Site Number 124918
🇨🇦Toronto, Canada
Investigational Site Number 376907
🇮🇱Safed, Israel
Investigational Site Number 840964
🇺🇸Perrysburg, Ohio, United States
Investigational Site Number 348901
🇭🇺Budapest, Hungary
Investigational Site Number 840994
🇺🇸Fort Worth, Texas, United States
Investigational Site Number 376904
🇮🇱Rehovot, Israel
Investigational Site Number 643927
🇷🇺Moscow, Russian Federation
Investigational Site Number 208914
🇩🇰Glostrup, Denmark
Investigational Site Number 208905
🇩🇰Hellerup, Denmark
Investigational Site Number 643922
🇷🇺Saint-Petersburg, Russian Federation
Investigational Site Number 643928
🇷🇺Moscow, Russian Federation
Investigational Site Number 710914
🇿🇦Bloemfontein, South Africa
Investigational Site Number 643932
🇷🇺Moscow, Russian Federation
Investigational Site Number 643911
🇷🇺Orenburg, Russian Federation
Investigational Site Number 410913
🇰🇷Uijeongbu, Korea, Republic of
Investigational Site Number 410905
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 410922
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 643904
🇷🇺Moscow, Russian Federation
Investigational Site Number 376901
🇮🇱Tel Aviv, Israel
Investigational Site Number 710913
🇿🇦Pretoria, South Africa
Investigational Site Number 643921
🇷🇺Ryazan, Russian Federation
Investigational Site Number 348903
🇭🇺Budapest, Hungary
Investigational Site Number 250903
🇫🇷Nantes, France
Investigational Site Number 410908
🇰🇷Anyang-Si, Korea, Republic of
Investigational Site Number 410901
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 376903
🇮🇱Kfar Saba, Israel
Investigational Site Number 348906
🇭🇺Szekesfehervar, Hungary
Investigational Site Number 804905
🇺🇦Kiev, Ukraine
Investigational Site Number 643924
🇷🇺Moscow, Russian Federation
Investigational Site Number 410915
🇰🇷Suwon, Korea, Republic of
Investigational Site Number 250906
🇫🇷Dijon, France
Investigational Site Number 410909
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 710917
🇿🇦Alberton, South Africa
Investigational Site Number 376902
🇮🇱Petach Tikva, Israel
Investigational Site Number 710904
🇿🇦Cape Town, South Africa
Investigational Site Number 710909
🇿🇦Bloemfontein, South Africa
Investigational Site Number 643908
🇷🇺Moscow, Russian Federation
Investigational Site Number 410920
🇰🇷Busan, Korea, Republic of
Investigational Site Number 710915
🇿🇦Somerset West, South Africa
Investigational Site Number 710918
🇿🇦Middelburg, South Africa
Investigational Site Number 410921
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 643931
🇷🇺Moscow, Russian Federation
Investigational Site Number 643914
🇷🇺St-Petersburg, Russian Federation
Investigational Site Number 643903
🇷🇺Kemerovo, Russian Federation
Investigational Site Number 410923
🇰🇷Gwangju, Korea, Republic of
Investigational Site Number 410914
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 804902
🇺🇦Uzhhorod, Ukraine
Investigational Site Number 208913
🇩🇰Esbjerg, Denmark
Investigational Site Number 208911
🇩🇰Herlev, Denmark
Investigational Site Number 208907
🇩🇰Hvidovre, Denmark
Investigational Site Number 208906
🇩🇰Køge, Denmark
Investigational Site Number 208908
🇩🇰Roskilde, Denmark
Investigational Site Number 208903
🇩🇰Silkeborg, Denmark
Investigational Site Number 840980
🇺🇸Birmingham, Alabama, United States
Investigational Site Number 840918
🇺🇸Phoenix, Arizona, United States
Investigational Site Number 840920
🇺🇸Miami, Florida, United States
Investigational Site Number 840973
🇺🇸Houston, Texas, United States
Investigational Site Number 840963
🇺🇸Cincinnati, Ohio, United States
Investigational Site Number 840944
🇺🇸Nashville, Tennessee, United States
Investigational Site Number 840939
🇺🇸Houston, Texas, United States
Investigational Site Number 250907
🇫🇷Montpellier Cedex 5, France
Investigational Site Number 250905
🇫🇷Nimes, France
Investigational Site Number 643925
🇷🇺Saint-Petersburg, Russian Federation
Investigational Site Number 410926
🇰🇷Daegu, Korea, Republic of
Investigational Site Number 410927
🇰🇷Wonju, Korea, Republic of
Investigational Site Number 410924
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 840962
🇺🇸Boynton Beach, Florida, United States
Investigational Site Number 840990
🇺🇸Spokane, Washington, United States
Investigational Site Number 643929
🇷🇺Saratov, Russian Federation
Investigational Site Number 840925
🇺🇸Tucson, Arizona, United States
Investigational Site Number 840991
🇺🇸Lincoln, California, United States
Investigational Site Number 840933
🇺🇸Chino, California, United States
Investigational Site Number 840302
🇺🇸Clearwater, Florida, United States
Investigational Site Number 840921
🇺🇸Vista, California, United States
Investigational Site Number 840987
🇺🇸Bradenton, Florida, United States
Investigational Site Number 840930
🇺🇸Thousand Oaks, California, United States
Investigational Site Number 840935
🇺🇸Jacksonville, Florida, United States
Investigational Site Number 840903
🇺🇸Miami, Florida, United States
Investigational Site Number 840943
🇺🇸Ocala, Florida, United States
Investigational Site Number 840940
🇺🇸Oxon Hill, Maryland, United States
Investigational Site Number 840960
🇺🇸Topeka, Kansas, United States
Investigational Site Number 840981
🇺🇸Oveido, Florida, United States
Investigational Site Number 840902
🇺🇸Evansville, Indiana, United States
Investigational Site Number 840988
🇺🇸St. Petersburg, Florida, United States
Investigational Site Number 840995
🇺🇸Meridian, Idaho, United States
Investigational Site Number 840961
🇺🇸Port Orange, Florida, United States
Investigational Site Number 840986
🇺🇸St. Petersburg, Florida, United States
Investigational Site Number 840998
🇺🇸St. Louis, Missouri, United States
Investigational Site Number 840949
🇺🇸Albuquerque, New Mexico, United States
Investigational Site Number 840974
🇺🇸New Windsor, New York, United States
Investigational Site Number 840938
🇺🇸Lexington, North Carolina, United States
Investigational Site Number 840976
🇺🇸Smithfield, North Carolina, United States
Investigational Site Number 840970
🇺🇸Lyndhust, Ohio, United States
Investigational Site Number 840906
🇺🇸Marion, Ohio, United States
Investigational Site Number 643906
🇷🇺Barnaul, Russian Federation
Investigational Site Number 710905
🇿🇦Cape Town, South Africa
Investigational Site Number 840917
🇺🇸Kansas City, Missouri, United States
Investigational Site Number 840985
🇺🇸Winston-Salem, North Carolina, United States
Investigational Site Number 840913
🇺🇸Charleston, South Carolina, United States
Investigational Site Number 840984
🇺🇸Richmond, Virginia, United States