High Cardiovascular Risk Patients With Hypercholesterolemia

Brief Summary: Primary Objective: To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab as add-on therapy to stable maximally tolerated daily statin therapy with or without other lipid-modifying therapy (LMT) in comparison with placebo after 24 weeks of treatment in high cardiovascular risk participants with hypercholesterolemia in South Korea and Taiwan. Secondary Objectives: To evaluate the effect of alirocumab in comparison with placebo on LDL-C after 12 weeks of treatment. To evaluate the effect of alirocumab on other lipid parameters: apolipoprotein B (Apo B), non high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), lipoprotein (a) (Lp [a]), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), and apolipoprotein A-1 (Apo A-1). To evaluate the safety and tolerability of alirocumab. To evaluate the development of anti-alirocumab antibodies (ADA).

Alirocumab

Alirocumab

auto-injection

75mg or 150mg

Primary Outcome Measures :
Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis [ Time Frame: 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 up to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).

Secondary Outcome Measures :
Percent Change From Baseline in Calculated LDL-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 up to Week 24 (i.e. up to 21 days after last injection) (on-treatment analysis).

Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.

Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis [ Time Frame: From Baseline to Week 24 ]
Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including available post-baseline on-treatment data up to Week 24 (i.e. up to 21 days after last injection).

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 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.

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 up to Week 24 (i.e. up to 21 days after last injection).

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 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.

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 up to Week 24 (i.e. up to 21 days after last injection).

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 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.

Percent Change From Baseline in Apo B at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.

Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.

Percent Change From Baseline in Total-C at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.

Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis [ Time Frame: From Baseline 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 up to Week 24 regardless of status on- or off-treatment were included in the imputation model.

Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-treatment Analysis [ Time Frame: From Baseline to Week 24 ]
Adjusted percentages at Week 24 were obtained from multiple imputation approach model including available post-baseline on-treatment data up to Week 24 (i.e. up to 21 days after last injection).

Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
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 up to Week 24 regardless of status on- or off-treatment were included in the imputation model.

Percent Change From Baseline in High Density Lipoprotein (HDL-C) at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.

Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
Adjusted means and standard errors at Week 24 were obtained from multiple imputation approach followed by robust regression model including all available post-baseline data up 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 [ Time Frame: From Baseline to Week 24 ]
Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.

Percent Change From Baseline in Lipoprotein(a) at Week 12- ITT Analysis [ Time Frame: From Baseline to Week 24 ]
Adjusted means and standard errors at Week 12 were obtained from multiple imputation approach followed by robust regression model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.

Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.

Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
Adjusted means and standard errors at Week 12 were obtained from multiple imputation approach followed by a robust regression model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.

Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.

Inclusion criteria:

Participants with hypercholesterolemia and established coronary heart disease (CHD) or CHD risk equivalents who are not adequately controlled with a maximally tolerated daily dose of statin with or without other LMT, both at stable dose for at least 4 weeks prior to screening visit (Week -3).

Exclusion criteria:

Aged <18 years or legal age of adulthood, whichever was greater.
Participants without established CHD or CHD risk equivalent.
LDL-C <70 mg/dL (<1.81 mmol/L) in participants with a history of documented cardiovascular disease.
LDL-C <100 mg/dL (<2.59 mmol/L) in participants without a history of documented cardiovascular disease.
Not on a stable dose of LMT (including statin) for at least 4 weeks prior to the screening visit (Week -3) or between screening to randomization visits.
Currently taking a statin other than atorvastatin, rosuvastatin or simvastatin.
Atorvastatin, rosuvastatin or simvastatin was not taken daily or not taken at a registered dose.
Daily doses above atorvastatin 80 mg, rosuvastatin 20 mg or simvastatin 40 mg.
Fasting serum triglycerides >400 mg/dL (>4.52 mmol/L) at the screening period.
The above information is not intended to contain all considerations relevant to a participants's potential participation in a clinical trial.