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OpenTrials
Completed

NCT Number: NCT01709513

Study of Alirocumab (REGN727/SAR236553) in Patients With Primary Hypercholesterolemia and Moderate, High, or Very High Cardiovascular (CV) Risk, Who Are Intolerant to Statins (ODYSSEY ALTERNATIVE)

This is a randomized, double-blind, double-dummy, active-controlled, parallel-group, multi-national, multi-center study to compare alirocumab (REGN727/SAR236553) versus ezetimibe in participants with primary hypercholesterolemia and moderate, high, or very high CV risk, who are intolerant to statins. An atorvastatin arm is added to determine that the population selected in the study is a truly statin intolerant population by assessing skeletal muscle-related adverse events.

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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

Feldkirch, Austria

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Who can participate

Healthy volunteers accepted: No

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

Inclusion:

  • Patients with primary hypercholesterolemia [Heterozygous Familial Hypercholesterolemia (heFH) or non-FH] with moderate, high or very high CV risk and a history of statin intolerance
  • Provide signed informed consent

Exclusion:

  • Calculated serum LDL-C <70 mg/dL (1.81 mmol/L) and very high CV risk at the screening visit
  • Calculated serum LDL-C <100 mg/dL (2.59 mmol/L) and high or moderate CV risk at the screening visit
  • A 10-year fatal cardiovascular disease risk score <1% at the screening visit

(The inclusion/ exclusion criteria provided above is not intended to contain all considerations relevant to a patient's potential participation in this clinical trial).

Treatment and study plan

atorvastatin

Drug

Atorvastatin over-encapsulated tablets.

ezetimibe

Drug

Ezetimibe over-encapsulated tablet.

Other names: Zetia

Alirocumab

Drug

Alirocumab SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.

Other names: REGN727/SAR236553

Placebo

Drug

Placebo for alirocumab, ezitimibe and atorvastatin.

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 24

    Calculated LDL-C values were obtained from Friedewald formula. 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 outcomes

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

    Time frame: From Baseline to Week 24

    Calculated LDL-C values were obtained from Friedewald formula. 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 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first) (on-treatment analysis).

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

    Time frame: From Baseline to Week 12

    Calculated LDL-C values were obtained from Friedewald formula. 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.

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

    Time frame: From Baseline to Week 12

    Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first) (on-treatment analysis).

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

    Time frame: 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.

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

    Time frame: From Baseline to Week 24

    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 24 (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 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.

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

    Time frame: From Baseline to Week 24

    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 24 (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 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.

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

    Time frame: From Baseline to Week 12

    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.

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

    Time frame: From Baseline to Week 12

    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.

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

    Time frame: From Baseline to Week 12

    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.

  12. Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis

    Time frame: Up to Week 24

    Adjusted percentages at Week 24 were obtained from a 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 (ITT analysis).

  13. Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis

    Time frame: Up to Week 24

    Adjusted percentages at Week 24 were obtained from a multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first (on-treatment analysis).

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

    Time frame: Up to Week 24

    Adjusted percentages at Week 24 were obtained from a 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 (ITT analysis).

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

    Time frame: Up to Week 24

    Adjusted percentages at Week 24 were obtained from a multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first (on-treatment analysis).

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

    Time frame: From Baseline to Week 24

    Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.

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

    Time frame: 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.

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

    Time frame: From Baseline to Week 24

    Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.

  19. Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis

    Time frame: 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.

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

    Time frame: From Baseline to Week 12

    Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.

  21. Percent Change in HDL-C From Baseline to Week 12 -- ITT Analysis

    Time frame: From Baseline to Week 12

    Least-squares (LS) means and standard errors (SE) taken from MMRM (mixed-effect model with repeated measures) analysis

  22. Percent Change in Fasting Triglycerides From Baseline to Week 12 -- ITT Analysis

    Time frame: From Baseline to Week 12

    Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.

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

    Time frame: From Baseline to Week 12

    Least squares (LS) means and standard errors (SE) taken from MMRM (mixed effect model with repeated measures) analysis.

Other outcomes

  1. Percentage of Participants Who Experienced Skeletal Muscle-related Adverse Event (AE)

    Time frame: From Baseline up to Week 24

    Skeletal muscle-related adverse events were a predefined category including myalgia, muscle spasms, muscular weakness, musculoskeletal stiffness and muscle fatigue. Events that developed during treatment emergent adverse events period (the time from the first double-blindstudy treatment [injection or capsules, whichever came first] up to the day of the last double-blind injection + 70 days ) are reported.

  2. Percent Change From Baseline in Calculated LDL-C at Week 24 Versus Atorvastatin - Raw Data Description - Intent-To-Treat (ITT) Analysis

    Time frame: From Baseline up to Week 24

Sponsors and collaborators

Lead sponsor

Regeneron Pharmaceuticals

Industry

Collaborators

  • Sanofi

Registry information

Official study title

A Randomized, Double-Blind, Double-Dummy, Active-Controlled Study to Evaluate the Efficacy and Safety of REGN727/SAR236553 in Patients With Primary Hypercholesterolemia Who Are Intolerant to Statins

Important dates

Study start
2012
Primary completion
2014
Study completion
2017
First posted
Oct 18, 2012
Registry last updated
Jun 23, 2020

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.

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