Hypercholesterolemia
Conditions
Brief summary
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 in comparison with ezetimibe after 24 weeks of treatment in participants with hypercholesterolemia. 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
Detailed description
The maximum study duration was 34 weeks per participant, including a 24-week randomized treatment period.
Interventions
DRUGAlirocumab
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.
DRUGEzetimibe
One over-encapsulated tablet orally once daily at approximately the same time of the day with or without food.
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.
One capsule orally once daily at approximately the same time of the day with or without food..
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
Exclusion criteria
* Age \< 18 or legal age of adulthood, whichever was greater * LDL-C \< 100 mg/dL (\< 2.59 mmol/L) or \> 190 mg/dL (\> 4.9 mmol/L) * Fasting serum triglycerides (TG) \> 400 mg/dL (\> 4.52 mmol/L) * Known history of homozygous or heterozygous familial hypercholesterolemia The above information was not intended to contain all considerations relevant to a participant'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 from Week 4 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 Apolipoprotein B (Apo B) at Week 24 - ITT Analysis | 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. |
| 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 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. |
| 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 from MMRM model including all available post-baseline data from Week 4 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 from MMRM model including all available post-baseline data from Week 4 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 from MMRM model including all available post-baseline data from Week 4 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 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. |
| Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis | Up 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 from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model. |
| Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis | Up to Week 24 | Adjusted percentages at Week 24 from multiple imputation approach model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. |
| 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 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. |
| Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis | 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. |
| 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 from MMRM model including all available post-baseline data from Week 4 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 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 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 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 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 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 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 from MMRM model including all available post-baseline data from Week 4 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 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. |
| 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 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. |
Countries
Belgium, Finland, Netherlands, United States
Participant flow
Recruitment details
The study was conducted at 8 centers in 4 countries. A total of 204 participants were screened between July 2012 and November 2012, 101 of whom were screen failures. Screen failures were mainly due to exclusion criteria met.
Pre-assignment details
Randomization was stratified according to the diabetes mellitus status. Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 1:1 ratio ( alirocumab:ezetimibe) after confirmation of selection criteria. 103 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Ezetimibe 10 mg Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks. | 51 |
| Alirocumab 75/Up to 150 mg Q2W SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8. | 52 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 5 |
| Overall Study | Consent withdrawn by participant | 0 | 1 |
| Overall Study | Participant moved | 0 | 1 |
| Overall Study | Poor compliance to protocol | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Site scheduling error | 1 | 1 |
Baseline characteristics
| Characteristic | Ezetimibe 10 mg | Alirocumab 75/Up to 150 mg Q2W | Total |
|---|---|---|---|
| Age, Continuous | 59.6 years STANDARD_DEVIATION 5.3 | 60.8 years STANDARD_DEVIATION 4.6 | 60.2 years STANDARD_DEVIATION 5 |
| Calculated LDL-C in mg/dL | 138.3 mg/dL STANDARD_DEVIATION 24.5 | 141.1 mg/dL STANDARD_DEVIATION 27.1 | 139.7 mg/dL STANDARD_DEVIATION 25.8 |
| Calculated LDL-C in mmol/L | 3.58 mmol/L STANDARD_DEVIATION 0.6 | 3.65 mmol/L STANDARD_DEVIATION 0.7 | 3.62 mmol/L STANDARD_DEVIATION 0.7 |
| Sex: Female, Male Female | 24 Participants | 24 Participants | 48 Participants |
| Sex: Female, Male Male | 27 Participants | 28 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 27 / 51 | 25 / 52 |
| serious Total, serious adverse events | 1 / 51 | 1 / 52 |
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 from Week 4 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: all randomized participants with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe 10 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis | -15.6 percent change | Standard Error 3.1 |
| Alirocumab 75/Up to 150 mg Q2W | Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis | -47.2 percent change | Standard Error 3 |
Comparison: Alirocumab group was compared to ezetimibe group using an appropriate contrast statement.p-value: <0.000195% CI: [-40.2, -23]Mixed Models Analysis
Secondary
Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 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 from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model.
Time frame: Up to Week 24
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ezetimibe 10 mg | Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis | 32.2 percentage of participants |
| Alirocumab 75/Up to 150 mg Q2W | Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis | 88.1 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: [8.7, 139]Regression, Logistic
Secondary
Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis
Adjusted percentages at Week 24 from multiple imputation approach model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time frame: Up to Week 24
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ezetimibe 10 mg | Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis | 2.4 percentage of participants |
| Alirocumab 75/Up to 150 mg Q2W | Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis | 59.4 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: [8.8, 556]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 from MMRM model including all available post-baseline data from Week 4 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 (MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe 10 mg | Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis | -2.2 percent change | Standard Error 1.4 |
| Alirocumab 75/Up to 150 mg Q2W | Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis | 2.3 percent change | Standard Error 1.4 |
Secondary
Percent Change From Baseline in 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 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 |
|---|---|---|---|
| Ezetimibe 10 mg | Percent Change From Baseline in Apo B at Week 12 - ITT Analysis | -11.7 percent change | Standard Error 2.1 |
| Alirocumab 75/Up to 150 mg Q2W | Percent Change From Baseline in Apo B at Week 12 - ITT Analysis | -37.3 percent change | Standard Error 2.1 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-31.5, -19.8]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 from MMRM model including all available post-baseline data from Week 4 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 |
|---|---|---|---|
| Ezetimibe 10 mg | Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24 - ITT Analysis | -0.6 percent change | Standard Error 1.6 |
| Alirocumab 75/Up to 150 mg Q2W | Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24 - ITT Analysis | 4.7 percent change | Standard Error 1.6 |
Secondary
Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24 - ITT Analysis
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.
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 |
|---|---|---|---|
| Ezetimibe 10 mg | Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24 - ITT Analysis | -11.0 percent change | Standard Error 2.4 |
| Alirocumab 75/Up to 150 mg Q2W | Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24 - ITT Analysis | -36.7 percent change | Standard Error 2.3 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-32.3, -19.2]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 from MMRM including all available post-baseline data from Week 4 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 |
|---|---|---|---|
| Ezetimibe 10 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis | -19.6 percent change | Standard Error 2.6 |
| Alirocumab 75/Up to 150 mg Q2W | Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis | -48.1 percent change | Standard Error 2.6 |
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: [-35.7, -21.2]Mixed Models Analysis
Secondary
Percent Change From Baseline in Fasting Triglycerides 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 24 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe 10 mg | Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis | -2.3 percent change | Standard Error 3.5 |
| Alirocumab 75/Up to 150 mg Q2W | Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis | -12.2 percent change | Standard Error 3.4 |
Secondary
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
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 24 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe 10 mg | Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis | -10.8 percent change | Standard Error 4.3 |
| Alirocumab 75/Up to 150 mg Q2W | Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis | -11.9 percent change | Standard Error 4.2 |
Secondary
Percent Change From Baseline in 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 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 |
|---|---|---|---|
| Ezetimibe 10 mg | Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis | 1.6 percent change | Standard Error 2 |
| Alirocumab 75/Up to 150 mg Q2W | Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis | 9.0 percent change | Standard Error 2 |
Secondary
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis
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.
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 |
|---|---|---|---|
| Ezetimibe 10 mg | Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis | 1.6 percent change | Standard Error 1.9 |
| Alirocumab 75/Up to 150 mg Q2W | Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis | 6.0 percent change | Standard Error 1.9 |
Secondary
Percent Change From Baseline in Lipoprotein (a) 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 24 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe 10 mg | Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis | -14.2 percent change | Standard Error 3.7 |
| Alirocumab 75/Up to 150 mg Q2W | Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis | -17.2 percent change | Standard Error 3.7 |
Secondary
Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis
Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 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 |
|---|---|---|---|
| Ezetimibe 10 mg | Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis | -12.3 percent change | Standard Error 3.8 |
| Alirocumab 75/Up to 150 mg Q2W | Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis | -16.7 percent change | Standard Error 3.7 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: 0.401395% CI: [-14.8, 5.9]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 from MMRM model including all available post-baseline data from Week 4 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 |
|---|---|---|---|
| Ezetimibe 10 mg | Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis | -16.7 percent change | Standard Error 2.4 |
| Alirocumab 75/Up to 150 mg Q2W | Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis | -42.5 percent change | Standard Error 2.3 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-32.4, -19.2]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 from MMRM model including all available post-baseline data from Week 4 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 |
|---|---|---|---|
| Ezetimibe 10 mg | Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis | -15.1 percent change | Standard Error 2.9 |
| Alirocumab 75/Up to 150 mg Q2W | Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis | -40.6 percent change | Standard Error 2.8 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-33.5, -17.4]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 from MMRM model including all available post-baseline data from Week 4 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 |
|---|---|---|---|
| Ezetimibe 10 mg | Percent Change From Baseline in Total-C at Week 12 - ITT Analysis | -12.0 percent change | Standard Error 1.7 |
| Alirocumab 75/Up to 150 mg Q2W | Percent Change From Baseline in Total-C at Week 12 - ITT Analysis | -30.3 percent change | Standard Error 1.7 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-23.1, -13.5]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 from MMRM model including all available post-baseline data from Week 4 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 |
|---|---|---|---|
| Ezetimibe 10 mg | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis | -10.9 percent change | Standard Error 2.2 |
| Alirocumab 75/Up to 150 mg Q2W | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis | -29.6 percent change | Standard Error 2.1 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-24.7, -12.7]Mixed Models Analysis