Hypercholesterolemia
Conditions
Brief summary
This is a randomized, double-blind, active-comparator, parallel-group study in patients at high cardiovascular risk with nonfamilial hypercholesterolemia or heterozygous familial hypercholesterolemia (heFH).
Interventions
DRUGAlirocumab
Alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.
DRUGAtorvastatin
Atorvastatin over-encapsulated tablets orally.
DRUGEzetimibe
Ezetimibe over-encapsulated tablet orally.
DRUGRosuvastatin
Rosuvastatin over-encapsulated tablets orally.
DRUGPlacebo
Placebo for alirocumab and ezetimibe.
Sponsors
Sanofi
Regeneron Pharmaceuticals
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
1. Patients with screening (visit 1) LDL-C greater than or equal to 70 mg/dL with documented CVD, not adequately controlled with a daily dose of atorvastatin. OR 2. Patients with screening (visit 1) LDL-C greater than or equal to 100 mg/dL at high risk for CVD who are not adequately controlled with a daily dose of atorvastatin.
Exclusion criteria
1. LDL-C greater than 250 mg/dL 2. LDL-C less than 70 mg/dL at the screening visit in patients with history of documented CVD 3. LDL-C less than 100 mg/dL at the screening visit in patients without history of documented CHD or non-CHD CVD, but with other risk factors 4. TG greater than 400 mg/dL 5. Homozygous FH (clinically or previous genotyping) 6. Currently taking a statin that is not atorvastatin 7. Currently taking Ezetimibe (EZE) 8. Not on a stable dose of allowable lipid modifying treatments (LMT) (The inclusion/
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 | 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
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis | From Baseline to Week 24 | 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 (ITT analysis). |
| Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | From Baseline to Week 24 | 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 \[whatever atorvastatin, rosuvastatin or ezetimibe\], whichever came first) (on-treatment analysis). |
| 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 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 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 from Week 4 to Week 24 (ie. up to 21 days after last injection or 3 days after the last capsule \[whatever atorvastatin, rosuvastatin or ezetimibe\], whichever came first). |
| 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 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 from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule \[whatever atorvastatin, rosuvastatin or ezetimibe\], whichever came first). |
| 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 Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching 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 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). |
| Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis | 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 \[whatever atorvastatin, rosuvastatin or ezetimibe\], whichever came first) (on-treatment analysis). |
| Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis | 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). |
| Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis | 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 \[whatever atorvastatin, rosuvastatin or ezetimibe\], whichever came first (on-treatment analysis). |
| 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 from a 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 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 Fasting Triglycerides at Week 24 - ITT Analysis | From Baseline to Week 24 | Adjusted means and standard errors at Week 24 from from a 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 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 Lipoprotein(a) at Week 12 - ITT Analysis | From Baseline to Week 24 | Adjusted means and standard errors at Week 12 from from a 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 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 Fasting Triglycerides at Week 12 - ITT Analysis | From Baseline to Week 24 | Adjusted means and standard errors at Week 12 from from a 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 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. |
| Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis | 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 \[whatever atorvastatin, rosuvastatin or ezetimibe\], whichever came first (on-treatment analysis). |
Countries
Australia, Canada, France, Germany, Italy, Mexico, Spain, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 85 sites in 9 countries. Overall, 859 subjects were screened between 24 October 2012 and 26 September 2013, 504 of whom were screen failures. Screen failures ware mainly due to exclusion criteria met.
Pre-assignment details
Randomization was stratified according to prior history of myocardial infarction or ischemic stroke, and intensity of statin treatment (atorvastatin 20 or 40 mg). Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 1:1:1:1:1:1:1 ratio after confirmation of selection criteria.
Participants by arm
| Arm | Count |
|---|---|
| Atorvastatin 40 mg Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received atorvastatin 40 mg over-encapsulated tablets orally once daily (QD), placebo for alirocumab SC injection every two weeks (Q2W), and placebo for ezetimibe over-encapsulated tablets orally QD added to stable Lipid-Modifying Therapy (LMT) for 24 weeks. | 57 |
| Ezetimibe 10 mg + Atorvastatin 20 mg Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received ezetimibe 10 mg over-encapsulated tablets orally QD, atorvastatin 20 mg over-encapsulated tablets orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks. | 55 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received Alirocumab 75 mg SC injection Q2W, atorvastatin 20 mg over-encapsulated tablets orally QD, and placebo for ezetimibe over-encapsulated tablets orally QD 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) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history. | 57 |
| Atorvastatin 80 mg Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received Atorvastatin 80 mg over-encapsulated tablets orally QD, placebo for alirocumab SC injection Q2W, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks. | 47 |
| Rosuvastatin 40 mg Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received rosuvastatin 40 mg over-encapsulated tablets orally QD, placebo for alirocumab SC injection Q2W, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks. | 45 |
| Ezetimibe 10 mg + Atorvastatin 40 mg Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received ezetimibe 10 mg over-encapsulated tablets orally QD, atorvastatin 40 mg over-encapsulated tablets orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks. | 47 |
| Alirocumab 75 mg/ up to 150 mg + Atorvastatin 40 mg Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received alirocumab 75 mg SC injection Q2W, atorvastatin 40 mg over-encapsulated tablets orally QD, and placebo for ezetimibe over-encapsulated tablets orally QD 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) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history. | 47 |
| Total | 355 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 3 | 5 | 3 | 1 | 1 | 2 |
| Overall Study | Other than specified | 7 | 8 | 5 | 5 | 5 | 4 | 4 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Poor compliance to protocol | 2 | 4 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Randomized but not treated | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Subject moved | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Atorvastatin 40 mg | Ezetimibe 10 mg + Atorvastatin 20 mg | Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | Atorvastatin 80 mg | Rosuvastatin 40 mg | Ezetimibe 10 mg + Atorvastatin 40 mg | Alirocumab 75 mg/ up to 150 mg + Atorvastatin 40 mg | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 63 years STANDARD_DEVIATION 9.91 | 65.7 years STANDARD_DEVIATION 8.96 | 62.2 years STANDARD_DEVIATION 10.03 | 63.2 years STANDARD_DEVIATION 10.89 | 57.5 years STANDARD_DEVIATION 9.96 | 63.9 years STANDARD_DEVIATION 10.33 | 64.2 years STANDARD_DEVIATION 10.36 | 62.9 years STANDARD_DEVIATION 10.2 |
| LDL-C in mmol/L | 2.957 mmol/L STANDARD_DEVIATION 0.773 | 2.599 mmol/L STANDARD_DEVIATION 0.765 | 2.692 mmol/L STANDARD_DEVIATION 0.905 | 2.813 mmol/L STANDARD_DEVIATION 0.97 | 2.844 mmol/L STANDARD_DEVIATION 1.011 | 2.562 mmol/L STANDARD_DEVIATION 0.756 | 3.016 mmol/L STANDARD_DEVIATION 0.968 | 2.723 mmol/L STANDARD_DEVIATION 0.884 |
| Low density lipoprotein cholesterol (LDL-C) in mg/dL | 100.3 mg/dL STANDARD_DEVIATION 29.8 | 100.4 mg/dL STANDARD_DEVIATION 29.5 | 103.9 mg/dL STANDARD_DEVIATION 34.9 | 108.6 mg/dL STANDARD_DEVIATION 37.5 | 109.8 mg/dL STANDARD_DEVIATION 39 | 98.9 mg/dL STANDARD_DEVIATION 29.2 | 116.4 mg/dL STANDARD_DEVIATION 37.4 | 105.1 mg/dL STANDARD_DEVIATION 34.1 |
| Sex: Female, Male Female | 22 Participants | 24 Participants | 24 Participants | 14 Participants | 13 Participants | 11 Participants | 16 Participants | 124 Participants |
| Sex: Female, Male Male | 35 Participants | 31 Participants | 33 Participants | 33 Participants | 32 Participants | 36 Participants | 31 Participants | 231 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 17 / 57 | 24 / 55 | 15 / 57 | 18 / 47 | 23 / 45 | 12 / 46 | 19 / 47 |
| serious Total, serious adverse events | 2 / 57 | 5 / 55 | 3 / 57 | 4 / 47 | 2 / 45 | 2 / 46 | 1 / 47 |
Outcome results
Primary
Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-treat (ITT) Analysis
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).
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 |
|---|---|---|---|
| Atorvastatin 40 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-treat (ITT) Analysis | -5 percent change | Standard Error 4.6 |
| Ezetimibe 10 mg + Atorvastatin 20 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-treat (ITT) Analysis | -20.5 percent change | Standard Error 4.7 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-treat (ITT) Analysis | -44.1 percent change | Standard Error 4.5 |
| Atorvastatin 80 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-treat (ITT) Analysis | -4.8 percent change | Standard Error 4.2 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-treat (ITT) Analysis | -21.4 percent change | Standard Error 4.2 |
| Ezetimibe 10 mg + Atorvastatin 40 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-treat (ITT) Analysis | -22.6 percent change | Standard Error 4.3 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-treat (ITT) Analysis | -54 percent change | Standard Error 4.3 |
Comparison: Alirocumab group was compared to the corresponding active control group using an appropriate contrast statement.p-value: <0.000199% CI: [-55.9, -22.2]Mixed Models Analysis
Comparison: As described in statistical analysis 1 of the endpoint.p-value: =0.000499% CI: [-40.7, -6.5]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-65, -33.5]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-48.4, -16.9]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-47.4, -15.4]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 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).
Time frame: Up to Week 24
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atorvastatin 40 mg | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis | 16.0 percentage of participants |
| Ezetimibe 10 mg + Atorvastatin 20 mg | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis | 50.3 percentage of participants |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis | 79.2 percentage of participants |
| Atorvastatin 80 mg | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis | 10.2 percentage of participants |
| Rosuvastatin 40 mg | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis | 42.2 percentage of participants |
| Ezetimibe 10 mg + Atorvastatin 40 mg | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis | 54.2 percentage of participants |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis | 77.2 percentage of participants |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant) for atorvastatin 40 mg baseline stratification). Statistical analysis used a multiple imputation approach followed by a Logistic regression model.p-value: <0.000199% CI: [14.7, 927.5]Regression, Logistic
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [2.5, 68.8]Regression, Logistic
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: =0.000499% CI: [1.9, 51.9]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 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 \[whatever atorvastatin, rosuvastatin or ezetimibe\], whichever came first (on-treatment analysis).
Time frame: Up to Week 24
Population: mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atorvastatin 40 mg | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis | 20.0 percentage of participants |
| Ezetimibe 10 mg + Atorvastatin 20 mg | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis | 55.1 percentage of participants |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis | 82.3 percentage of participants |
| Atorvastatin 80 mg | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis | 10.5 percentage of participants |
| Rosuvastatin 40 mg | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis | 42.4 percentage of participants |
| Ezetimibe 10 mg + Atorvastatin 40 mg | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis | 55.3 percentage of participants |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis | 83.7 percentage of participants |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant) for atorvastatin 40 mg baseline stratification). Statistical analysis used a multiple imputation approach followed by a Logistic regression model.p-value: <0.000199% CI: [17.3, 1520.5]Regression, Logistic
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [3.1, 126.3]Regression, Logistic
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: =0.000299% CI: [2.2, 88.1]Regression, Logistic
Secondary
Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis
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).
Time frame: Up to Week 24
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atorvastatin 40 mg | Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis | 34.5 percentage of participants |
| Ezetimibe 10 mg + Atorvastatin 20 mg | Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis | 68.4 percentage of participants |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis | 87.2 percentage of participants |
| Atorvastatin 80 mg | Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis | 18.5 percentage of participants |
| Rosuvastatin 40 mg | Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis | 62.2 percentage of participants |
| Ezetimibe 10 mg + Atorvastatin 40 mg | Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis | 65.1 percentage of participants |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg | Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis | 84.6 percentage of participants |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant). Statistical analysis used a multiple imputation approach followed by a Logistic regression model.p-value: <0.000199% CI: [3.9, 71.7]Regression, Logistic
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: =0.028499% CI: [0.8, 14.6]Regression, Logistic
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [11.6, 596.8]Regression, Logistic
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: =0.002599% CI: [1.3, 38.3]Regression, Logistic
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: =0.001199% CI: [1.6, 52.2]Regression, Logistic
Secondary
Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis
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 \[whatever atorvastatin, rosuvastatin or ezetimibe\], whichever came first (on-treatment analysis).
Time frame: Up to Week 24
Population: mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atorvastatin 40 mg | Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis | 37.8 percentage of participants |
| Ezetimibe 10 mg + Atorvastatin 20 mg | Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis | 72.2 percentage of participants |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis | 91.2 percentage of participants |
| Atorvastatin 80 mg | Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis | 18.5 percentage of participants |
| Rosuvastatin 40 mg | Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis | 64.0 percentage of participants |
| Ezetimibe 10 mg + Atorvastatin 40 mg | Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis | 66.2 percentage of participants |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg | Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis | 90.0 percentage of participants |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant) for atorvastatin 40 mg baseline stratification). Statistical analysis used a multiple imputation approach followed by a Logistic regression model.p-value: <0.000199% CI: [14.2, 1157]Regression, Logistic
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: =0.001599% CI: [1.6, 75.4]Regression, Logistic
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: =0.000899% CI: [1.8, 101.1]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 (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin 40 mg | Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis | -0.8 percent change | Standard Error 1.5 |
| Ezetimibe 10 mg + Atorvastatin 20 mg | Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis | 1.7 percent change | Standard Error 1.4 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis | 5.4 percent change | Standard Error 1.4 |
| Atorvastatin 80 mg | Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis | 1.6 percent change | Standard Error 1.7 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis | 5.6 percent change | Standard Error 1.7 |
| Ezetimibe 10 mg + Atorvastatin 40 mg | Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis | 1.6 percent change | Standard Error 1.7 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg | Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis | 9.4 percent change | Standard Error 1.7 |
Secondary
Percent Change From Baseline in 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 analyzed: participants of the ITT population with one baseline and at least one post-baseline Apo A-1 value on- or off-treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin 40 mg | Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis | 1.2 percent change | Standard Error 1.5 |
| Ezetimibe 10 mg + Atorvastatin 20 mg | Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis | 1.0 percent change | Standard Error 1.6 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis | 7.6 percent change | Standard Error 1.5 |
| Atorvastatin 80 mg | Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis | 2.2 percent change | Standard Error 2 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis | 4.7 percent change | Standard Error 1.9 |
| Ezetimibe 10 mg + Atorvastatin 40 mg | Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis | -1.8 percent change | Standard Error 1.9 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg | Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis | 5.8 percent change | Standard Error 2 |
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 |
|---|---|---|---|
| Atorvastatin 40 mg | Percent Change From Baseline in Apo B at Week 12 - ITT Analysis | -6.9 percent change | Standard Error 2.8 |
| Ezetimibe 10 mg + Atorvastatin 20 mg | Percent Change From Baseline in Apo B at Week 12 - ITT Analysis | -13.1 percent change | Standard Error 2.8 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | Percent Change From Baseline in Apo B at Week 12 - ITT Analysis | -38.4 percent change | Standard Error 2.7 |
| Atorvastatin 80 mg | Percent Change From Baseline in Apo B at Week 12 - ITT Analysis | -9.5 percent change | Standard Error 2.5 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Apo B at Week 12 - ITT Analysis | -14.1 percent change | Standard Error 2.5 |
| Ezetimibe 10 mg + Atorvastatin 40 mg | Percent Change From Baseline in Apo B at Week 12 - ITT Analysis | -20.3 percent change | Standard Error 2.5 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg | Percent Change From Baseline in Apo B at Week 12 - ITT Analysis | -36.2 percent change | Standard Error 2.5 |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).p-value: <0.000199% CI: [-41.6, -21.3]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-35.4, -15.2]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-35.9, -17.5]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-31.5, -12.9]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-25.2, -6.6]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 from Week 4 to Week 24 (ie. up to 21 days after last injection or 3 days after the last capsule \[whatever atorvastatin, rosuvastatin or ezetimibe\], whichever came first).
Time frame: From Baseline to Week 24
Population: Participants analyzed: participants of the mITT population with one baseline and at least one post-baseline Apo B value on-treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin 40 mg | Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis | -5.1 percent change | Standard Error 3.3 |
| Ezetimibe 10 mg + Atorvastatin 20 mg | Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis | -12.6 percent change | Standard Error 3.5 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis | -37.7 percent change | Standard Error 3.2 |
| Atorvastatin 80 mg | Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis | -4.4 percent change | Standard Error 3.4 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis | -12.8 percent change | Standard Error 3.4 |
| Ezetimibe 10 mg + Atorvastatin 40 mg | Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis | -16.3 percent change | Standard Error 3.4 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg | Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis | -42.7 percent change | Standard Error 3.5 |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).p-value: <0.000199% CI: [-44.6, -20.6]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-37.3, -12.8]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-51.2, -25.4]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-42.6, -17.1]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-39.4, -13.4]Mixed Models Analysis
Secondary
Percent Change From Baseline in Apolipoprotein (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 analyzed: participants of the ITT population with one baseline and at least one post-baseline Apo B value on- or off-treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin 40 mg | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis | -4.4 percent change | Standard Error 3.5 |
| Ezetimibe 10 mg + Atorvastatin 20 mg | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis | -10.1 percent change | Standard Error 3.6 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis | -33.7 percent change | Standard Error 3.4 |
| Atorvastatin 80 mg | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis | -3.5 percent change | Standard Error 3.3 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis | -10.9 percent change | Standard Error 3.2 |
| Ezetimibe 10 mg + Atorvastatin 40 mg | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis | -14.3 percent change | Standard Error 3.3 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis | -41.9 percent change | Standard Error 3.4 |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).p-value: <0.000199% CI: [-42, -16.6]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-36.6, -10.7]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-50.8, -26]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-43.2, -18.6]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-40.1, -15.1]Mixed Models Analysis
Secondary
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
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 (ITT analysis).
Time frame: From Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin 40 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis | -8.5 percent change | Standard Error 3.9 |
| Ezetimibe 10 mg + Atorvastatin 20 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis | -22.6 percent change | Standard Error 3.9 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis | -48.4 percent change | Standard Error 3.8 |
| Atorvastatin 80 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis | -14.5 percent change | Standard Error 3.2 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis | -23.3 percent change | Standard Error 3.2 |
| Ezetimibe 10 mg + Atorvastatin 40 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis | -29.7 percent change | Standard Error 3.2 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis | -50.5 percent change | Standard Error 3.2 |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).p-value: <0.000199% CI: [-54, -25.6]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-40, -11.6]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-47.7, -24.3]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-39.2, -15.4]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-32.8, -8.9]Mixed Models Analysis
Secondary
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
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 \[whatever atorvastatin, rosuvastatin or ezetimibe\], whichever came first) (on-treatment analysis).
Time frame: From Baseline to Week 24
Population: mITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin 40 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | -9.2 percent change | Standard Error 3.1 |
| Ezetimibe 10 mg + Atorvastatin 20 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | -27.1 percent change | Standard Error 3.1 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | -53.7 percent change | Standard Error 3.1 |
| Atorvastatin 80 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | -14.6 percent change | Standard Error 3.2 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | -23.3 percent change | Standard Error 3.2 |
| Ezetimibe 10 mg + Atorvastatin 40 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | -30.7 percent change | Standard Error 3.2 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | -50.9 percent change | Standard Error 3.2 |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).p-value: <0.000199% CI: [-55.8, -33.1]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-38, -15.2]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-48.1, -24.5]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-39.6, -15.8]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-32.2, -8.2]Mixed Models Analysis
Secondary
Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis
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 \[whatever atorvastatin, rosuvastatin or ezetimibe\], whichever came first) (on-treatment analysis).
Time frame: From Baseline to Week 24
Population: Modified ITT (mITT) population: 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 |
|---|---|---|---|
| Atorvastatin 40 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis | -6.1 percent change | Standard Error 4.6 |
| Ezetimibe 10 mg + Atorvastatin 20 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis | -23.7 percent change | Standard Error 4.7 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis | -48.6 percent change | Standard Error 4.5 |
| Atorvastatin 80 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis | -5.0 percent change | Standard Error 4.4 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis | -22.9 percent change | Standard Error 4.4 |
| Ezetimibe 10 mg + Atorvastatin 40 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis | -24.5 percent change | Standard Error 4.5 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis | -57.8 percent change | Standard Error 4.5 |
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 1% level.p-value: <0.000199% CI: [-59.2, -25.7]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: =0.000299% CI: [-41.9, -7.8]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-69.2, -36.5]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-51.3, -18.6]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-50, -16.8]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 from a 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: From Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin 40 mg | Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis | -4.7 percent change | Standard Error 4.2 |
| Ezetimibe 10 mg + Atorvastatin 20 mg | Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis | 0.5 percent change | Standard Error 4.2 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis | -12.4 percent change | Standard Error 4.2 |
| Atorvastatin 80 mg | Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis | -4.6 percent change | Standard Error 4 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis | -3.7 percent change | Standard Error 4.1 |
| Ezetimibe 10 mg + Atorvastatin 40 mg | Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis | -16.8 percent change | Standard Error 4 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg | Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis | -12.1 percent change | Standard Error 4 |
Secondary
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
Adjusted means and standard errors at Week 24 from from a 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: From Baseline to Week 24
Population: ITT population: all randomized and treated participants with one baseline and at least one post-baseline fasting triglycerides value on- or off-treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin 40 mg | Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis | -6.7 percent change | Standard Error 3.7 |
| Ezetimibe 10 mg + Atorvastatin 20 mg | Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis | -3.3 percent change | Standard Error 4.1 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis | -12.0 percent change | Standard Error 3.7 |
| Atorvastatin 80 mg | Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis | -7.3 percent change | Standard Error 4.1 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis | -0.5 percent change | Standard Error 4 |
| Ezetimibe 10 mg + Atorvastatin 40 mg | Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis | -13.9 percent change | Standard Error 4.1 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg | Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis | -19.1 percent change | Standard Error 4.1 |
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 |
|---|---|---|---|
| Atorvastatin 40 mg | Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis | -3.2 percent change | Standard Error 1.8 |
| Ezetimibe 10 mg + Atorvastatin 20 mg | Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis | -1.7 percent change | Standard Error 1.8 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis | 4.1 percent change | Standard Error 1.8 |
| Atorvastatin 80 mg | Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis | 3.0 percent change | Standard Error 2.6 |
| Rosuvastatin 40 mg | Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis | 4.6 percent change | Standard Error 2.7 |
| Ezetimibe 10 mg + Atorvastatin 40 mg | Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis | 4.6 percent change | Standard Error 2.7 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg | Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis | 8.5 percent change | Standard Error 2.7 |
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 analyzed: participants of the ITT population with one baseline and at least one post-baseline HDL-C value on- or off-treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin 40 mg | Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis | 1.9 percent change | Standard Error 2 |
| Ezetimibe 10 mg + Atorvastatin 20 mg | Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis | -0.1 percent change | Standard Error 2.1 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis | 4.8 percent change | Standard Error 2 |
| Atorvastatin 80 mg | Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis | 4.7 percent change | Standard Error 2.7 |
| Rosuvastatin 40 mg | Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis | 5.7 percent change | Standard Error 2.7 |
| Ezetimibe 10 mg + Atorvastatin 40 mg | Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis | 2.0 percent change | Standard Error 2.7 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg | Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis | 7.7 percent change | Standard Error 2.7 |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant) for atorvastatin 40 mg baseline stratification).p-value: =0.445699% CI: [-7, 12.9]Mixed Models Analysis
Secondary
Percent Change From Baseline in Lipoprotein(a) at Week 12 - ITT Analysis
Adjusted means and standard errors at Week 12 from from a 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: From Baseline to Week 24
Population: Lipoprotein (a) ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin 40 mg | Percent Change From Baseline in Lipoprotein(a) at Week 12 - ITT Analysis | -11.7 percent change | Standard Error 4 |
| Ezetimibe 10 mg + Atorvastatin 20 mg | Percent Change From Baseline in Lipoprotein(a) at Week 12 - ITT Analysis | -5.4 percent change | Standard Error 4 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | Percent Change From Baseline in Lipoprotein(a) at Week 12 - ITT Analysis | -24.0 percent change | Standard Error 4 |
| Atorvastatin 80 mg | Percent Change From Baseline in Lipoprotein(a) at Week 12 - ITT Analysis | -1.6 percent change | Standard Error 4.5 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Lipoprotein(a) at Week 12 - ITT Analysis | 11.5 percent change | Standard Error 4.6 |
| Ezetimibe 10 mg + Atorvastatin 40 mg | Percent Change From Baseline in Lipoprotein(a) at Week 12 - ITT Analysis | 7.9 percent change | Standard Error 4.5 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg | Percent Change From Baseline in Lipoprotein(a) at Week 12 - ITT Analysis | -27.9 percent change | Standard Error 4.5 |
Secondary
Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis
Adjusted means and standard errors at Week 24 from from a 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: From Baseline to Week 24
Population: Participants analyzed: participants of the ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin 40 mg | Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis | -20.2 percent change | Standard Error 4 |
| Ezetimibe 10 mg + Atorvastatin 20 mg | Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis | -10.6 percent change | Standard Error 4.4 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis | -23.6 percent change | Standard Error 4 |
| Atorvastatin 80 mg | Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis | -9.7 percent change | Standard Error 4.1 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis | -4.9 percent change | Standard Error 3.7 |
| Ezetimibe 10 mg + Atorvastatin 40 mg | Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis | 0.2 percent change | Standard Error 3.9 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg | Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis | -30.8 percent change | Standard Error 4.1 |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant) for atorvastatin 40 mg baseline stratification). Statistical analysis used a multiple imputation approach followed by a robust regression model.p-value: =0.000499% CI: [-36.3, -5.9]Regression, Robust
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-40.2, -11.6]Regression, Robust
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-45.6, -16.4]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 |
|---|---|---|---|
| Atorvastatin 40 mg | Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis | -7.1 percent change | Standard Error 3.2 |
| Ezetimibe 10 mg + Atorvastatin 20 mg | Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis | -17.2 percent change | Standard Error 3.2 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis | -40.6 percent change | Standard Error 3.2 |
| Atorvastatin 80 mg | Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis | -13.0 percent change | Standard Error 2.6 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis | -19.8 percent change | Standard Error 2.7 |
| Ezetimibe 10 mg + Atorvastatin 40 mg | Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis | -27.5 percent change | Standard Error 2.7 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg | Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis | -42.3 percent change | Standard Error 2.7 |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).p-value: <0.000199% CI: [-45.3, -21.6]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-35.2, -11.6]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-39, -19.6]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-32.3, -12.7]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-24.7, -4.9]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 from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule \[whatever atorvastatin, rosuvastatin or ezetimibe\], whichever came first).
Time frame: From Baseline to Week 24
Population: Participants analyzed: participants of the mITT population with one baseline and at least one post-baseline Non-HDL-C value on-treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin 40 mg | Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis | -7.5 percent change | Standard Error 3.8 |
| Ezetimibe 10 mg + Atorvastatin 20 mg | Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis | -18.1 percent change | Standard Error 4 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis | -40.5 percent change | Standard Error 3.7 |
| Atorvastatin 80 mg | Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis | -7.0 percent change | Standard Error 3.7 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis | -18.4 percent change | Standard Error 3.7 |
| Ezetimibe 10 mg + Atorvastatin 40 mg | Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis | -23.3 percent change | Standard Error 3.8 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg | Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis | -50.5 percent change | Standard Error 3.8 |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).p-value: <0.000199% CI: [-47, -19]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-36.6, -8.1]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-57.4, -29.7]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-46, -18.3]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-41.4, -13.2]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 analyzed: participants of the ITT population with one baseline and at least one post-baseline non-HDL-C value on- or off-treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin 40 mg | Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis | -6.3 percent change | Standard Error 3.9 |
| Ezetimibe 10 mg + Atorvastatin 20 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 4 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis | -36.7 percent change | Standard Error 3.9 |
| Atorvastatin 80 mg | Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis | -6.5 percent change | Standard Error 3.6 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis | -17.4 percent change | Standard Error 3.6 |
| Ezetimibe 10 mg + Atorvastatin 40 mg | Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis | -21.0 percent change | Standard Error 3.7 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg | Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis | -47.6 percent change | Standard Error 3.7 |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).p-value: <0.000199% CI: [-44.7, -16.1]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: =0.000299% CI: [-36.1, -7.1]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-54.7, -27.5]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-43.7, -16.6]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-40.3, -12.8]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 |
|---|---|---|---|
| Atorvastatin 40 mg | Percent Change From Baseline in Total-C at Week 12 - ITT Analysis | -6.5 percent change | Standard Error 2.4 |
| Ezetimibe 10 mg + Atorvastatin 20 mg | Percent Change From Baseline in Total-C at Week 12 - ITT Analysis | -13.2 percent change | Standard Error 2.4 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | Percent Change From Baseline in Total-C at Week 12 - ITT Analysis | -29.0 percent change | Standard Error 2.4 |
| Atorvastatin 80 mg | Percent Change From Baseline in Total-C at Week 12 - ITT Analysis | -9.9 percent change | Standard Error 2.1 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Total-C at Week 12 - ITT Analysis | -13.5 percent change | Standard Error 2.1 |
| Ezetimibe 10 mg + Atorvastatin 40 mg | Percent Change From Baseline in Total-C at Week 12 - ITT Analysis | -19.2 percent change | Standard Error 2.1 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg | Percent Change From Baseline in Total-C at Week 12 - ITT Analysis | -29.0 percent change | Standard Error 2.1 |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).p-value: <0.000199% CI: [-31.4, -13.8]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-24.6, -7]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-26.9, -11.4]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-23.3, -7.6]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: =0.001599% CI: [-17.7, -1.9]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 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 analyzed: participants of the ITT population with one baseline and at least one post-baseline Total-C value on- or off-treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin 40 mg | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis | -4.0 percent change | Standard Error 2.7 |
| Ezetimibe 10 mg + Atorvastatin 20 mg | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis | -11.2 percent change | Standard Error 2.8 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis | -27.1 percent change | Standard Error 2.7 |
| Atorvastatin 80 mg | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis | -4.8 percent change | Standard Error 2.8 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis | -11.7 percent change | Standard Error 2.8 |
| Ezetimibe 10 mg + Atorvastatin 40 mg | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis | -15.2 percent change | Standard Error 2.9 |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis | -33.6 percent change | Standard Error 2.9 |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).p-value: <0.000199% CI: [-32.9, -13.2]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-25.8, -5.8]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-39.4, -18.4]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-32.4, -11.4]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000199% CI: [-29.1, -7.7]Mixed Models Analysis