Skip to main content
OpenTrials
Completed

NCT Number: NCT01644188

Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Ezetimibe on Top of Statin in High Cardiovascular Risk Patients With Hypercholesterolemia (ODYSSEY COMBO II)

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

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Hypercholesterolemia Dyslipidemias Hyperlipidemias Lipid Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Investigational Site Number 124902, Brampton, Canada

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Participants with hypercholesterolemia and established coronary heart disease (CHD) or CHD risk equivalents who were not adequately controlled with a maximally tolerated daily dose of statin at stable dose for at least 4 weeks prior to the screening visit (Week -2).

Exclusion criteria

  • Age < 18 or legal age of adulthood, whichever was greater
  • Participants without established CHD or CHD risk equivalents
  • LDL-C <70 mg/dL (<1.81 mmol/L) and participants with a history of documented cardiovascular disease
  • LDL-C <100 mg/dL (<2.59 mmol/L) and participants without a history of documented CV disease
  • Fasting serum triglycerides >400 mg/dL (>4.52 mmol/L)

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Treatment and study plan

Alirocumab

Drug

1 mL subcutaneous injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using the autoinjector.

Other names: REGN727/SAR236553, Praluent

Placebo (for alirocumab)

Drug

1 mL subcutaneous injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using the autoinjector.

ezetimibe

Drug

One over-encapsulated tablet orally once daily at approximately the same time of the day with or without food.

Placebo (for Ezetimibe)

Drug

One capsule once daily orally at approximately the same time of the day with or without food.

Lipid Modifying Therapy (LMT)

Drug

Statin (rosuvastatin, simvastatin or atorvastatin) at stable dose.

Primary outcomes

  1. Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-treat (ITT) Analysis

    Time frame: 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 outcomes

  1. Percent Change From Baseline in Calculated LDL--C at Week 24 - On--Treatment Analysis

    Time frame: 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).

  2. Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis

    Time frame: 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.

  3. Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis

    Time frame: 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).

  4. Percent Change From Baseline in Apolipoprotein B (Apo-B) at Week 24 - ITT Analysis

    Time frame: 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.

  5. Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis

    Time frame: 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).

  6. Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis

    Time frame: 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.

  7. Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis

    Time frame: 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).

  8. Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis

    Time frame: 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.

  9. Percent Change From Baseline in Apo-B at Week 12 - ITT Analysis

    Time frame: 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.

  10. Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis

    Time frame: 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.

  11. Percent Change From Baseline in Total-C at Week 12 - ITT Analysis

    Time frame: 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.

  12. Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis

    Time frame: 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.

  13. Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis

    Time frame: 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.

  14. Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis

    Time frame: 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).

  15. Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis

    Time frame: 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.

  16. Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis

    Time frame: 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.

  17. Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis

    Time frame: 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.

  18. Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24 - ITT Analysis

    Time frame: 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.

  19. Percent Change From Baseline in Lipoprotein(a) at Week 12 - ITT Analysis

    Time frame: 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.

  20. Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis

    Time frame: 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.

  21. Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis

    Time frame: 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.

  22. Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis

    Time frame: 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.

Other outcomes

  1. Percent Change From Baseline in Calculated LDL-C at Week 52 - On-Treatment Analysis

    Time frame: From Baseline to Week 52

    Adjusted LS means and standard errors at Week 52 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).

  2. Percent Change From Baseline in Calculated LDL-C at Week 104 - ITT Analysis

    Time frame: From Baseline to Week 104

    Adjusted LS means and standard errors at Week 104 from MMRM including all available post-baseline data from Week 4 to Week 104 regardless of status on-or off-treatment.

  3. Percent Change From Baseline in Calculated LDL-C at Week 104 - On-Treatment Analysis

    Time frame: From Baseline to Week 104

    Adjusted LS means and standard errors at Week 104 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 104 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first).

Sponsors and collaborators

Lead sponsor

Sanofi

Industry

Collaborators

  • Regeneron Pharmaceuticals

Registry information

Official study title

A Randomized, Double-Blind, Parallel Group Study to Evaluate the Efficacy and Safety of SAR236553/REGN727 Versus Ezetimibe in High Cardiovascular Risk Patients With Hypercholesterolemia Not Adequately Controlled With Their Statin Therapy

Important dates

Study start
2012
Primary completion
2014
Study completion
2015
First posted
Jul 18, 2012
Registry last updated
Aug 4, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.