Hypercholesterolemia
Conditions
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).
Detailed description
The maximum study duration was approximately 35 weeks per participant, including up to 3 weeks screening period, 24 weeks double-blind treatment period, and 8 weeks follow-up period.
Interventions
Solution for injection, one subcutaneous injection in the abdomen with a disposable auto-injector.
DRUGAlirocumab
Solution for injection, one subcutaneous injection in the abdomen with a disposable auto-injector.
Statins (Rosuvastatin, Simvastatin or Atorvastatin) at stable dose with or without other LMT as clinically indicated.
Sponsors
Regeneron Pharmaceuticals
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis | 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
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 24 - On-Treatment Analysis | 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). |
| Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-treatment Analysis | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
Countries
South Korea, Taiwan
Participant flow
Recruitment details
The study was conducted at 27 centers in South Korea and Taiwan. Overall 316 participants were screened between January and September 2015, of whom 117 were screen failures. Screen failures were mainly due to exclusion criteria met.
Pre-assignment details
Randomization was stratified according to prior history of myocardial infarction (MI) or ischemic stroke, intensity of statin treatment and country. Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 1:1 ratio (Placebo:Alirocumab). A total of 199 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Q2W Placebo (for alirocumab) SC injection Q2W added to stable LMT for 24 weeks. | 102 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8. | 97 |
| Total | 199 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | End treatment visit outside visit window | 0 | 4 |
| Overall Study | Last injection missed | 2 | 2 |
| Overall Study | Other than specified above | 0 | 2 |
| Overall Study | Poor compliance to protocol | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo Q2W | Alirocumab 75 mg Q2W/Up to 150 mg Q2W | Total |
|---|---|---|---|
| Age, Continuous | 60.1 years STANDARD_DEVIATION 9.1 | 61.2 years STANDARD_DEVIATION 10.4 | 60.6 years STANDARD_DEVIATION 9.7 |
| Calculated LDL-C in mmol/L | 2.572 mmol/L STANDARD_DEVIATION 0.653 | 2.513 mmol/L STANDARD_DEVIATION 0.721 | 2.543 mmol/L STANDARD_DEVIATION 0.686 |
| Sex: Female, Male Female | 21 Participants | 14 Participants | 35 Participants |
| Sex: Female, Male Male | 81 Participants | 83 Participants | 164 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 102 | 1 / 97 |
| other Total, other adverse events | 15 / 102 | 19 / 97 |
| serious Total, serious adverse events | 10 / 102 | 17 / 97 |
Outcome results
Primary
Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis
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).
Time frame: From Baseline to Week 24
Population: ITT population that included all randomized participants with one baseline and at least one post-baseline calculated LDL-C on- or off-treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis | 6.3 percent change | Standard Error 2.9 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W | Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis | -57.1 percent change | Standard Error 3 |
Comparison: Alirocumab group was compared to placebo group using an appropriate contrast statement.p-value: <0.000195% CI: [-71.6, -55.2]Mixed Models Analysis
Secondary
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Q2W | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis | 14.2 percentage of participants |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis | 85.8 percentage of participants |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [18.4, 119.4]Regression, Logistic
Secondary
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-treatment Analysis
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).
Time frame: From Baseline to Week 24
Population: mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Q2W | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-treatment Analysis | 14.1 percentage of participants |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-treatment Analysis | 88.8 percentage of participants |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [23.3, 210.8]Regression, Logistic
Secondary
Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Population: Apo A-1 ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis | 1.5 percent change | Standard Error 1.1 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W | Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis | 4.5 percent change | Standard Error 1.1 |
Secondary
Percent Change From Baseline in Apo B at Week 12 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Population: Apo B ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Apo B at Week 12 - ITT Analysis | 5.2 percent change | Standard Error 1.8 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W | Percent Change From Baseline in Apo B at Week 12 - ITT Analysis | -40.9 percent change | Standard Error 1.8 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-51.2, -41]Mixed Models Analysis
Secondary
Percent Change From Baseline in Apo B at Week 24 - On-treatment Analysis
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).
Time frame: From Baseline to Week 24
Population: Participants of the mITT population with one baseline and at least one post-baseline Apo B value on-treatment (Apo B mITT population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Apo B at Week 24 - On-treatment Analysis | 3.8 percent change | Standard Error 2.1 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W | Percent Change From Baseline in Apo B at Week 24 - On-treatment Analysis | -45.4 percent change | Standard Error 2.2 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-55.3, -43.1]Mixed Models Analysis
Secondary
Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Population: Participants of the ITT population with one baseline and at least one post-baseline Apo A-1 value on- or off-treatment (Apo A-1 ITT population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24 - ITT Analysis | 3.2 percent change | Standard Error 1.2 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W | Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24 - ITT Analysis | 4.5 percent change | Standard Error 1.2 |
Secondary
Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Population: Participants of the ITT population with one baseline and at least one post-baseline Apo B value on- or off-treatment (Apo B ITT population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis | 4.1 percent change | Standard Error 2.3 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis | -42.3 percent change | Standard Error 2.4 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-53, -39.7]Mixed Models Analysis
Secondary
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis | 4.7 percent change | Standard Error 2.2 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W | Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis | -57.9 percent change | Standard Error 2.2 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-68.8, -56.3]Mixed Models Analysis
Secondary
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 up to Week 24 (i.e. up to 21 days after last injection).
Time frame: From Baseline to Week 24
Population: mITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | 4.7 percent change | Standard Error 2.2 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | -58.4 percent change | Standard Error 2.2 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-69.2, -57]Mixed Models Analysis
Secondary
Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis
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).
Time frame: From Baseline to Week 24
Population: Modified ITT (mITT) population that included all randomized and treated participants with one baseline and at least one post-baseline calculated LDL-C value on-treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis | 6.0 Percent Change | Standard Error 2.7 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W | Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis | -60.2 Percent Change | Standard Error 2.8 |
Comparison: A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 0.05 level.p-value: <0.000195% CI: [-73.9, -58.4]Mixed Models Analysis
Secondary
Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis | 2.113 percent change | Standard Error 3.192 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W | Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis | -6.999 percent change | Standard Error 3.252 |
Secondary
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis | -3.627 percent change | Standard Error 3.111 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W | Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis | -8.143 percent change | Standard Error 3.204 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: 0.31195% CI: [-13.25, 4.219]Regression, Robust
Secondary
Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Population: HDL-C ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis | 2.0 percent change | Standard Error 1.5 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W | Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis | 7.1 percent change | Standard Error 1.6 |
Secondary
Percent Change From Baseline in High Density Lipoprotein (HDL-C) at Week 24 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Population: Participants of the ITT population with one baseline and at least one post-baseline HDL-C value on- or off-treatment (HDL-C ITT population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in High Density Lipoprotein (HDL-C) at Week 24 - ITT Analysis | 6.2 percent change | Standard Error 1.7 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W | Percent Change From Baseline in High Density Lipoprotein (HDL-C) at Week 24 - ITT Analysis | 13.8 percent change | Standard Error 1.8 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: 0.002995% CI: [2.6, 12.4]Mixed Models Analysis
Secondary
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 including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Lipoprotein(a) at Week 12- ITT Analysis | -1.676 percent change | Standard Error 2.732 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W | Percent Change From Baseline in Lipoprotein(a) at Week 12- ITT Analysis | -33.601 percent change | Standard Error 2.778 |
Secondary
Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis | -2.251 percent change | Standard Error 2.962 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W | Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis | -35.862 percent change | Standard Error 3.011 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-41.883, -25.338]Regression, Robust
Secondary
Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Population: Non-HDL-C ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis | 3.9 percent change | Standard Deviation 1.8 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W | Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis | -47.3 percent change | Standard Deviation 1.9 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-56.4, -46.1]Mixed Models Analysis
Secondary
Percent Change From Baseline in Non-HDL-C at Week 24 - On-treatment Analysis
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).
Time frame: From Baseline to Week 24
Population: Participants of the mITT population with one baseline and at least one post-baseline non-HDL-C value on-treatment (non-HDL-C mITT population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Non-HDL-C at Week 24 - On-treatment Analysis | 4.1 percent change | Standard Deviation 2.2 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W | Percent Change From Baseline in Non-HDL-C at Week 24 - On-treatment Analysis | -50.1 percent change | Standard Deviation 2.3 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-60.6, -47.8]Mixed Models Analysis
Secondary
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Population: Participants of the ITT population with one baseline and at least one post-baseline non-HDL-C value on- or off-treatment (non-HDL-C ITT population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis | 4.3 percent change | Standard Error 2.4 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W | Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis | -47.2 percent change | Standard Error 2.5 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-58.4, -44.6]Mixed Models Analysis
Secondary
Percent Change From Baseline in Total-C at Week 12 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Population: Total-C ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Total-C at Week 12 - ITT Analysis | 2.8 percent change | Standard Error 1.4 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W | Percent Change From Baseline in Total-C at Week 12 - ITT Analysis | -32.9 percent change | Standard Error 1.4 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant.p-value: <0.000195% CI: [-39.7, -31.9]Mixed Models Analysis
Secondary
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Population: Participants of the ITT population with one baseline and at least one post-baseline Total-C value on- or off-treatment (Total-C ITT population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis | 4.0 percent change | Standard Deviation 1.8 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis | -31.2 percent change | Standard Deviation 1.8 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-40.3, -30.1]Mixed Models Analysis