Hypercholesterolemia
Conditions
Brief summary
To evaluate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab (REGN727/SAR236553) as an add-on therapy to other LMT in patients with hypercholesterolemia at high cardiovascular (CV) risk.
Interventions
DRUGEzetimibe
Ezetimibe over-encapsulated tablets orally.
DRUGAlirocumab
Alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.
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 LDL-C greater than or equal to 70 mg/dL at the screening visit and who are not adequately controlled with a stable daily dose of rosuvastatin, with or without other LMT. OR 2. Patients with screening LDL-C greater than or equal to 100 mg/dL who are not adequately controlled with a stable daily dose of rosuvastatin before the screening visit, with or without other LMT.
Exclusion criteria
1. LDL-C less than 70 mg/dL at the screening visit in patients with history of documented cardiovascular disease (CVD) 2. LDL-C less than 100 mg/dL at the screening visit in patients without history of documented coronary heart disease (CHD) or non-CHD CVD, but with other risk factors 3. Homozygous familial hypercholesterolemia (FH) (clinically or previous genotyping) 4. Recent (within 3 months prior to the screening visit) myocardial infarction (MI), unstable angina leading to hospitalization, percutaneous coronary intervention (PCI), coronary bypass graft surgery (CABG), uncontrolled cardiac arrhythmia, stroke, transient ischemic attack, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease 5. Newly diagnosed (within 3 months prior to randomization visit) or poorly controlled diabetes 6. Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins (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 12 | 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 12 | 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 \[whatever rosuvastatin or ezetimibe\], 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 \[whatever rosuvastatin or ezetimibe\], 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 \[whatever rosuvastatin or ezetimibe\], 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 12 | 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 12 | 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 12 | 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 | Calculated LDL-C values were obtained from Friedewald formula. 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 (ie. up to 21 days after last injection or 3 days after the last capsule \[whatever rosuvastatin or ezetimibe\], 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 | Calculated LDL-C values were obtained from Friedewald formula. 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 | Calculated LDL-C values were obtained from Friedewald formula. 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 \[whatever rosuvastatin or ezetimibe\], 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 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 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 12 | Adjusted means and standard errors at Week 12 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 12 | 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 12 | Adjusted means and standard errors at Week 12 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 12 | 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 | Calculated LDL-C values were obtained from Friedewald formula. 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 \[whatever rosuvastatin or ezetimibe\], 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 79 sites in 8 countries. Overall, 672 participants were screened between 24 October 2012 and 27 September 2013, 367 of whom were screen failures. Screen failures were mainly due to exclusion criteria met.
Pre-assignment details
Randomization was stratified according to prior history of myocardial infarction or ischemic stroke, and intensity of statin treatment (rosuvastatin 10 or 20 mg). Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System (IVWRS) in a 1:1:1:1:1:1 ratio after confirmation of selection criteria.
Participants by arm
| Arm | Count |
|---|---|
| Rosuvastatin 20 mg Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks. | 48 |
| Ezetimibe 10 mg + Rosuvastatin 10 mg Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks. | 48 |
| Alirocumab 75/up to 150 + Rosuvastatin 10 mg Participants, who were receiving rosuvastatin 10 mg over-encapsulated tablet orally at baseline, received alirocumab 75 mg SC injection Q2W, rosuvastatin 10 mg over-encapsulated tablet orally QD, and placebo for ezetimibe over-encapsulated tablet 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. | 49 |
| Rosuvastatin 40 mg Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks. | 53 |
| Ezetimibe 10 mg + Rosuvastatin 20 mg Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks. | 53 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe 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. | 54 |
| Total | 305 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 6 | 3 | 3 | 2 | 2 |
| Overall Study | Other than specified | 2 | 6 | 5 | 4 | 7 | 9 |
| Overall Study | Participant moved | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Poor compliance to protocol | 1 | 2 | 2 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Rosuvastatin 20 mg | Ezetimibe 10 mg + Rosuvastatin 10 mg | Alirocumab 75/up to 150 + Rosuvastatin 10 mg | Rosuvastatin 40 mg | Ezetimibe 10 mg + Rosuvastatin 20 mg | Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 61.5 years STANDARD_DEVIATION 11.15 | 60.4 years STANDARD_DEVIATION 10.38 | 62.2 years STANDARD_DEVIATION 11.11 | 60.6 years STANDARD_DEVIATION 10.11 | 63.1 years STANDARD_DEVIATION 10.2 | 57.9 years STANDARD_DEVIATION 8.86 | 60.9 years STANDARD_DEVIATION 10.4 |
| LDL-C in mmol/L | 2.743 mmol/L STANDARD_DEVIATION 0.933 | 2.653 mmol/L STANDARD_DEVIATION 1.085 | 2.78 mmol/L STANDARD_DEVIATION 0.684 | 2.924 mmol/L STANDARD_DEVIATION 1.122 | 3.082 mmol/L STANDARD_DEVIATION 1.243 | 3.065 mmol/L STANDARD_DEVIATION 0.834 | 2.882 mmol/L STANDARD_DEVIATION 1.009 |
| Low density lipoprotein cholesterol (LDL-C) in mg/dL | 105.9 mg/dL STANDARD_DEVIATION 36 | 102.4 mg/dL STANDARD_DEVIATION 41.9 | 107.3 mg/dL STANDARD_DEVIATION 26.4 | 112.9 mg/dL STANDARD_DEVIATION 43.3 | 119.0 mg/dL STANDARD_DEVIATION 48 | 118.3 mg/dL STANDARD_DEVIATION 32.2 | 111.3 mg/dL STANDARD_DEVIATION 39 |
| Sex: Female, Male Female | 15 Participants | 22 Participants | 18 Participants | 15 Participants | 22 Participants | 26 Participants | 118 Participants |
| Sex: Female, Male Male | 33 Participants | 26 Participants | 31 Participants | 38 Participants | 31 Participants | 28 Participants | 187 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 48 | 11 / 48 | 11 / 49 | 20 / 53 | 12 / 53 | 15 / 54 |
| serious Total, serious adverse events | 4 / 48 | 5 / 48 | 2 / 49 | 4 / 53 | 3 / 53 | 4 / 54 |
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 |
|---|---|---|---|
| Rosuvastatin 20 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis | -16.3 percent change | Standard Error 4.1 |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis | -14.4 percent change | Standard Error 4.4 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis | -50.6 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 | -15.9 percent change | Standard Error 7.1 |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis | -11.0 percent change | Standard Error 7.2 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis | -36.3 percent change | Standard Error 7.1 |
Comparison: Alirocumab group was compared to the corresponding active control group using an appropriate contrast statement.p-value: <0.000198.75% CI: [-49.2, -19.3]Mixed Models Analysis
Comparison: As described in statistical analysis 1 of the endpoint.p-value: <0.000198.75% CI: [-51.5, -20.7]Mixed Models Analysis
Comparison: As described in statistical analysis 1 of the endpoint.p-value: =0.045398.75% CI: [-45.8, 5.1]Mixed Models Analysis
Comparison: As described in statistical analysis 1 of the endpoint.p-value: =0.013698.75% CI: [-50.9, 0.3]Mixed Models Analysis
Secondary
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis
Calculated LDL-C values were obtained from Friedewald formula. 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) |
|---|---|---|
| Rosuvastatin 20 mg | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis | 31.3 percentage of participants |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis | 43.1 percentage of participants |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis | 77.8 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 | 29.9 percentage of participants |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis | 43.6 percentage of participants |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis | 60.1 percentage of participants |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification). Statistical analysis used a multiple imputation approach followed by a Logistic regression model.p-value: <0.000198.75% CI: [3.6, 96.2]Regression, Logistic
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000198.75% CI: [2.5, 53.1]Regression, Logistic
Secondary
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis
Calculated LDL-C values were obtained from Friedewald formula. 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 \[whatever rosuvastatin or ezetimibe\], whichever came first (on-treatment analysis).
Time frame: Up to Week 24
Population: mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rosuvastatin 20 mg | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis | 34.8 percentage of participants |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis | 46.7 percentage of participants |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis | 76.5 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 | 30.6 percentage of participants |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis | 45.1 percentage of participants |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis | 66.1 percentage of participants |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification). Statistical analysis used a multiple imputation approach followed by a Logistic regression model.p-value: <0.000198.75% CI: [2.4, 67.7]Regression, Logistic
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: =0.000298.75% CI: [2.4, 67.7]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
Calculated LDL-C values were obtained from Friedewald formula. 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) |
|---|---|---|
| Rosuvastatin 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 | 45.0 percentage of participants |
| Ezetimibe 10 mg + Rosuvastatin 10 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 | 57.2 percentage of participants |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 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 | 84.9 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 | 40.1 percentage of participants |
| Ezetimibe 10 mg + Rosuvastatin 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 | 52.2 percentage of participants |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 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 | 66.7 percentage of participants |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification). Statistical analysis used a multiple imputation approach followed by a Logistic regression model.p-value: <0.000198.75% CI: [2.6, 59.5]Regression, Logistic
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: =0.000798.75% CI: [1.8, 40.5]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
Calculated LDL-C values were obtained from Friedewald formula. 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 \[whatever rosuvastatin or ezetimibe\], whichever came first (on-treatment analysis).
Time frame: Up to Week 24
Population: mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rosuvastatin 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 | 47.0 percentage of participants |
| Ezetimibe 10 mg + Rosuvastatin 10 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 | 60.5 percentage of participants |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 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 | 86.4 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 | 41.3 percentage of participants |
| Ezetimibe 10 mg + Rosuvastatin 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 | 54.8 percentage of participants |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 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 | 70.4 percentage of participants |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification). Statistical analysis used a multiple imputation approach followed by a Logistic regression model.p-value: <0.000198.75% CI: [2.58, 88.2]Regression, Logistic
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: =0.00198.75% CI: [1.7, 56.7]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 12
Population: Apo A-1 ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin 20 mg | Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis | 4.0 percent change | Standard Error 1.6 |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis | 2.6 percent change | Standard Error 1.6 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis | 4.3 percent change | Standard Error 1.6 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis | 0.9 percent change | Standard Error 1.8 |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis | 1.8 percent change | Standard Error 1.8 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis | 9.1 percent change | Standard Error 1.8 |
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 |
|---|---|---|---|
| Rosuvastatin 20 mg | Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis | 5.4 percent change | Standard Error 1.9 |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis | 5.0 percent change | Standard Error 1.9 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis | 6.7 percent change | Standard Error 1.9 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis | 2.9 percent change | Standard Error 1.9 |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis | -0.9 percent change | Standard Error 1.9 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis | 6.7 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 12
Population: Apo B ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin 20 mg | Percent Change From Baseline in Apo B at Week 12 - ITT Analysis | -8.1 percent change | Standard Error 3.2 |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Apo B at Week 12 - ITT Analysis | -12.1 percent change | Standard Error 3.3 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Apo B at Week 12 - ITT Analysis | -36.1 percent change | Standard Error 3.2 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Apo B at Week 12 - ITT Analysis | -13.7 percent change | Standard Error 3.3 |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Apo B at Week 12 - ITT Analysis | -14.3 percent change | Standard Error 3.3 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Apo B at Week 12 - ITT Analysis | -29.0 percent change | Standard Error 3.3 |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification).p-value: <0.000198.75% CI: [-39.7, -16.5]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000198.75% CI: [-35.7, -12.3]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 \[whatever rosuvastatin or ezetimibe\], 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 |
|---|---|---|---|
| Rosuvastatin 20 mg | Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis | -8.8 percent change | Standard Error 2.6 |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis | -11.2 percent change | Standard Error 2.7 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis | -39.5 percent change | Standard Error 2.6 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis | -12.7 percent change | Standard Error 4 |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis | -12.6 percent change | Standard Error 4.1 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis | -30.4 percent change | Standard Error 4.2 |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification).p-value: <0.000198.75% CI: [-40.1, -21.3]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000198.75% CI: [-38, -18.7]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 |
|---|---|---|---|
| Rosuvastatin 20 mg | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis | -7.3 percent change | Standard Error 3 |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis | -9.7 percent change | Standard Error 3.1 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis | -36.5 percent change | Standard Error 3.1 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis | -9.8 percent change | Standard Error 4.1 |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis | -11.2 percent change | Standard Error 4.3 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis | -28.3 percent change | Standard Error 4.3 |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification).p-value: <0.000198.75% CI: [-40.1, -18.3]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000198.75% CI: [-37.9, -15.7]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 12
Population: ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin 20 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis | -17.1 percent change | Standard Error 4.1 |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis | -17.4 percent change | Standard Error 4.2 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis | -49.6 percent change | Standard Error 4.1 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis | -22.1 percent change | Standard Error 5.3 |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis | -19.3 percent change | Standard Error 5.4 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis | -32.3 percent change | Standard Error 5.2 |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification).p-value: <0.000198.75% CI: [-47.4, -17.9]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000198.75% CI: [-47, -17.5]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 \[whatever rosuvastatin or ezetimibe\], whichever came first) (on-treatment analysis).
Time frame: From Baseline to Week 12
Population: mITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin 20 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | -17.2 percent change | Standard Error 3.6 |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | -20.3 percent change | Standard Error 3.8 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | -52.6 percent change | Standard Error 3.6 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | -22.9 percent change | Standard Error 5.2 |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | -21.8 percent change | Standard Error 5.2 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | -35.1 percent change | Standard Error 5.2 |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification).p-value: <0.000198.75% CI: [-48.2, -22.5]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000198.75% CI: [-45.6, -19]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 (ie. up to 21 days after last injection or 3 days after the last capsule \[whatever rosuvastatin or ezetimibe\], 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 |
|---|---|---|---|
| Rosuvastatin 20 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis | -18.3 percent change | Standard Error 3.3 |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis | -20.3 percent change | Standard Error 3.6 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis | -53.5 percent change | Standard Error 3.5 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis | -17.0 percent change | Standard Error 6.9 |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis | -16.5 percent change | Standard Error 6.9 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis | -41.5 percent change | Standard Error 6.9 |
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 1.25 % level.p-value: <0.000198.75% CI: [-47.4, -23]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000198.75% CI: [-45.9, -20.5]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: =0.013198.75% CI: [-49.2, 0.2]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 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 12
Population: Fasting triglycerides ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin 20 mg | Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis | 8.1 percent change | Standard Error 4.1 |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis | -8.2 percent change | Standard Error 4.2 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis | -14 percent change | Standard Error 4.1 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis | -2.7 percent change | Standard Error 4 |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis | -12.4 percent change | Standard Error 4 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis | -10.1 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 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 |
|---|---|---|---|
| Rosuvastatin 20 mg | Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis | -1.8 percent change | Standard Error 4.5 |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis | -8.3 percent change | Standard Error 4.8 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis | -11.2 percent change | Standard Error 4.6 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis | -9.9 percent change | Standard Error 4.1 |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis | -11.1 percent change | Standard Error 4.3 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis | -8.7 percent change | Standard Error 4.5 |
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 12
Population: HDL-C ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin 20 mg | Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis | 0.7 percent change | Standard Error 2.1 |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis | 0.2 percent change | Standard Error 2.2 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis | 5.9 percent change | Standard Error 2.1 |
| Rosuvastatin 40 mg | Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis | 0.6 percent change | Standard Error 2.5 |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis | 3.1 percent change | Standard Error 2.5 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg | Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis | 8.0 percent change | Standard Error 2.5 |
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 |
|---|---|---|---|
| Rosuvastatin 20 mg | Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis | 1.7 percent change | Standard Error 2.4 |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis | 4.0 percent change | Standard Error 2.5 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis | 9.1 percent change | Standard Error 2.4 |
| Rosuvastatin 40 mg | Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis | 1.5 percent change | Standard Error 2.3 |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis | -1.8 percent change | Standard Error 2.3 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg | Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis | 7.2 percent change | Standard Error 2.3 |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification). Statistical analysis used a multiple imputation approach followed by a robust regression model.p-value: =0.031198.75% CI: [-1.2, 16.1]Regression, Robust
Secondary
Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis
Adjusted means and standard errors at Week 12 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 12
Population: Lipoprotein (a) ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin 20 mg | Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis | -0.7 percent change | Standard Error 3.5 |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis | -3.9 percent change | Standard Error 3.6 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis | -20.7 percent change | Standard Error 3.5 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis | 3.5 percent change | Standard Error 4.2 |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis | 7.9 percent change | Standard Error 4.1 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis | -16.0 percent change | Standard Error 4.2 |
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 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 |
|---|---|---|---|
| Rosuvastatin 20 mg | Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis | -4.0 percent change | Standard Error 4.3 |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis | -4.3 percent change | Standard Error 4.5 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis | -27.9 percent change | Standard Error 4.1 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis | -5.2 percent change | Standard Error 4.8 |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis | -5.8 percent change | Standard Error 4.6 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis | -22.7 percent change | Standard Error 5.1 |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification). Statistical analysis used a multiple imputation approach followed by a robust regression model.p-value: <0.000198.75% CI: [-38.6, -9.1]Regression, Robust
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: =0.000198.75% CI: [-39, -8.2]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 12
Population: Non-HDL-C ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin 20 mg | Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis | -11.7 percent change | Standard Error 3.5 |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis | -16.3 percent change | Standard Error 3.6 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis | -41.2 percent change | Standard Error 3.5 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis | -18.0 percent change | Standard Error 3.6 |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis | -18.7 percent change | Standard Error 3.7 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis | -29.8 percent change | Standard Error 3.6 |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification).p-value: <0.000198.75% CI: [-42.1, -16.9]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000198.75% CI: [-37.7, -12.2]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 \[whatever rosuvastatin or ezetimibe\], 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 |
|---|---|---|---|
| Rosuvastatin 20 mg | Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis | -12.9 percent change | Standard Error 2.8 |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis | -17.5 percent change | Standard Error 3.1 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis | -45.7 percent change | Standard Error 2.9 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis | -14.9 percent change | Standard Error 4.2 |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis | -18.2 percent change | Standard Error 4.2 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis | -35.6 percent change | Standard Error 4.3 |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification).p-value: <0.000198.75% CI: [-43.2, -22.4]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000198.75% CI: [-39.1, -17.3]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 |
|---|---|---|---|
| Rosuvastatin 20 mg | Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis | -11.3 percent change | Standard Error 3.4 |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis | -13.4 percent change | Standard Error 3.7 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis | -42.7 percent change | Standard Error 3.5 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis | -11.2 percent change | Standard Error 5.1 |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis | -12.9 percent change | Standard Error 5.2 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis | -31.4 percent change | Standard Error 5.2 |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification).p-value: <0.000198.75% CI: [-43.9, -18.9]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000198.75% CI: [-42.1, -16.4]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 12
Population: Total-C ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin 20 mg | Percent Change From Baseline in Total-C at Week 12 - ITT Analysis | -8.9 percent change | Standard Error 2.6 |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Total-C at Week 12 - ITT Analysis | -11.8 percent change | Standard Error 2.7 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Total-C at Week 12 - ITT Analysis | -29.0 percent change | Standard Error 2.6 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Total-C at Week 12 - ITT Analysis | -13.8 percent change | Standard Error 2.8 |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Total-C at Week 12 - ITT Analysis | -13.9 percent change | Standard Error 2.8 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Total-C at Week 12 - ITT Analysis | -19.4 percent change | Standard Error 2.7 |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification).p-value: <0.000198.75% CI: [-29.4, -10.7]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000198.75% CI: [-26.7, -7.7]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 |
|---|---|---|---|
| Rosuvastatin 20 mg | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis | -8.3 percent change | Standard Error 2.4 |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis | -8.7 percent change | Standard Error 2.6 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis | -28.9 percent change | Standard Error 2.5 |
| Rosuvastatin 40 mg | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis | -8.5 percent change | Standard Error 3.6 |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis | -12.4 percent change | Standard Error 3.6 |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis | -20.6 percent change | Standard Error 3.6 |
Comparison: Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification).p-value: <0.000198.75% CI: [-29.4, -11.8]Mixed Models Analysis
Comparison: Analysis description as per the statistical analysis 1 of this endpoint.p-value: <0.000198.75% CI: [-29.3, -11.2]Mixed Models Analysis