Primary Objective: To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab administration as add-on therapy to non-statin lipid modifying therapy (LMT) including diet therapy alone or the lowest strength of statin in comparison with placebo after 12 weeks of treatment in participants with hypercholesterolemia. Secondary Objective: * To evaluate the effect of two treatment regimens 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), triglyceride (TG), and apolipoprotein A-1 (Apo A-1). * To evaluate the safety and tolerability of alirocumab administration. * To evaluate the development of anti-alirocumab antibodies. * To evaluate the pharmacokinetic and pharmacodynamic profiles of alirocumab administration. * To evaluate the long-term safety in participants receiving open-label alirocumab administration.
The duration of study per participant was approximately 71 weeks consisting of a run-in period (4 weeks), a screening period (3 weeks), a double-blind treatment period (12 weeks), and an open-label treatment period (52 weeks).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
163
Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector.
Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector.
Atorvastatin 5 mg tablet orally.
Ezetimibe, Bezafibrate or Fenofibrate at stable dose as background therapy.
Stable cholesterol-lowering diet as background therapy.
Investigational Site Number 392028
Ageo-Shi, Japan
Investigational Site Number 392007
Chūōku, Japan
Investigational Site Number 392029
Chūōku, Japan
Investigational Site Number 392014
Fukui-shi, Japan
Investigational Site Number 392023
Hachioji-Shi, Japan
Investigational Site Number 392013
Itoshima-Shi, Japan
Investigational Site Number 392010
Kanazawa, Japan
Investigational Site Number 392024
Kasuga-Shi, Japan
Investigational Site Number 392004
Kawanishi-Shi, Japan
Investigational Site Number 392015
Kitakyushu-Shi, Japan
...and 20 more locations
Percent Change From Baseline in Calculated LDL-C at Week 12- Intent to Treat (ITT) Analysis
Adjusted Least-squares (LS) means and standard errors at Week 12 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 12 regardless of status on- or off-treatment were used in the model (ITT analysis).
Time frame: From Baseline to Week 12
Percent Change From Baseline in Calculated LDL-C at Week 12- On-Treatment Analysis
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 12 (i.e. up to 21 days after last double-blind injection).
Time frame: From Baseline to Week 12
Percent Change From Baseline in Calculated LDL-C to Averaged Week 10 to 12: ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment and assigning a weight of 0.5 for Week 10 and 12 time points.
Time frame: From Baseline to Week 12
Percent Change From Baseline in Calculated LDL-C to Averaged Week 10 to 12- On-Treatment Analysis
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 12 (i.e. up to 21 days after last double-blind injection) and assigning a weight of 0.5 for Week 10 and 12 time points.
Time frame: From Baseline to Week 12
Percent Change From Baseline in Apolipoprotein B (Apo-B) at Week 12: ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 12
Percent Change From Baseline in Apo-B at Week 12- On-Treatment Analysis
Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including available post-baseline on-treatment data at from Week 4 to Week 12 (i.e. up to 21 days after last double-blind injection).
Time frame: From Baseline to Week 12
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12: ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 12
Percent Change From Baseline in Non-HDL-C at Week 12- On-treatment Analysis
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 12 (i.e. up to 21 days after last double-blind injection).
Time frame: From Baseline to Week 12
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 12- ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 12
Percentage of Participants Reaching Calculated LDL-C Goal at Week 12- ITT Analysis
Calculated LDL-C goal was defined as calculated LDL-C \<100 mg/dL (2.59 mmol/L) for heterozygous familiar hypercholesterolemia (heFH) participants or non-familial hypercholesterolemia (non-FH) participants who had a history of documented CHD, or \<120 mg/dL (3.10 mmol/L) for non-FH participants who had a history of documented diseases or other risk factors as defined in JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012. Adjusted percentages at Week 12 were obtained from multiple imputation approach for handling of missing data. All available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment were included in the imputation model.
Time frame: Up to Week 12
Percentage of Participants Reaching Calculated LDL-C Goal at Week 12- On-Treatment Analysis
Calculated LDL-C goal was defined as calculated LDL-C \<100 mg/dL (2.59 mmol/L) for heFH participants or non-FH participants who had a history of documented CHD, or \<120 mg/dL (3.10 mmol/L) for non-FH participants who had a history of documented diseases or other risk factors as defined in JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012. Adjusted percentages at Week 12 from multiple imputation approach including available post-baseline on-treatment data from Week 4 to Week 12 (i.e. up to 21 days after last double-blind injection).
Time frame: Up to Week 12
Percent Change From Baseline in Lipoprotein (a) at Week 12: ITT Analysis
Adjusted means and standard errors at Week 12 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 12 regardless of status on- or off-treatment were included in the imputation model.
Time frame: From Baseline to Week 12
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12- ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 12
Percent Change From Baseline in Fasting Triglycerides (TGs) at Week 12: ITT Analysis
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 12 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 12
Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 12: ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 12
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