Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Alirocumab (REGN727/SAR236553) in Patients With Primary Hypercholesterolemia and Moderate, High, or Very High Cardiovascular (CV) Risk, Who Are Intolerant to Statins (ODYSSEY ALTERNATIVE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01709513
Recruitment Status : Completed
First Posted : October 18, 2012
Results First Posted : August 28, 2015
Last Update Posted : August 28, 2017
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Hypercholesterolemia
Interventions Drug: Atorvastatin
Drug: Ezetimibe
Drug: Alirocumab
Drug: Placebo
Enrollment 314
Recruitment Details The study was conducted at 67 sites in 8 countries. Overall, 519 participants were screened between 28 September 2012 and 11 August 2013, 158 of whom were screen failures. Screen failures were mainly due to exclusion criteria met. After screening, 361 participants entered into a 4-week single blind placebo run-in period.
Pre-assignment Details At the end of the single blind placebo run-in period, eligible participants were randomized to treatment arms centrally using a 2:2:1 (alirocumab:ezetimibe:atorvastatin) ratio. Randomization was stratified according to prior history of myocardial infarction or ischemic stroke. 314 participants were randomized.
Arm/Group Title Atorvastatin (Statin Rechallenge Arm) Ezetimibe (Active Comparator) Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description Atorvastatin 20 mg over-encapsulated tablets orally once daily (QD) for 24 weeks and placebo (for alirocumab) subcutaneous (SC) injection every two weeks (Q2W) for 24 weeks added to stable LMT. Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT. Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Period Title: Overall Study
Started 63 125 126
Treated 63 124 126
Completed 42 82 96
Not Completed 21 43 30
Reason Not Completed
Randomized but not treated             0             1             0
Adverse Event             16             31             23
Poor compliance to protocol             2             0             0
Other             3             11             7
Arm/Group Title Atorvastatin (Statin Rechallenge Arm) Ezetimibe (Active Comparator) Alirocumab 75 mg/ up to 150 mg Total
Hide Arm/Group Description Atorvastatin 20 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable lipid-modifying therapy (LMT). Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT. Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk. Total of all reporting groups
Overall Number of Baseline Participants 63 125 126 314
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 63 participants 125 participants 126 participants 314 participants
63.4  (9.5) 62.8  (10.1) 64.1  (9.0) 63.4  (9.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 63 participants 125 participants 126 participants 314 participants
Female
28
  44.4%
58
  46.4%
56
  44.4%
142
  45.2%
Male
35
  55.6%
67
  53.6%
70
  55.6%
172
  54.8%
Low Density Lipoprotein Cholesterol (LDL-C) in mg/dL   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 63 participants 125 participants 126 participants 314 participants
187.3  (59.5) 193.5  (70.9) 191.1  (72.7) 191.3  (69.3)
[1]
Measure Description: Calculated LDL-C values were obtained from Friedewald formula.
LDL-C in mmol/L   [1] 
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 63 participants 125 participants 126 participants 314 participants
4.85  (1.54) 5.011  (1.837) 4.951  (1.883) 4.954  (1.796)
[1]
Measure Description: Calculated LDL-C values were obtained from Friedewald formula.
1.Primary Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent--To-Treat (ITT) Analysis
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population: all randomized participants with one baseline and at least one post-baseline calculated LDL-C value on­ or off-treatment.
Arm/Group Title Ezetimibe Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description:
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 122 126
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-14.6  (2.2) -45.0  (2.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe, Alirocumab 75 mg/ up to 150 mg
Comments Alirocumab group was compared to the corresponding active control group using an appropriate contrast statement.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -30.4
Confidence Interval (2-Sided) 95%
-36.6 to -24.2
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 24 - On--Treatment Analysis
Hide Description 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, whichever came first) (on-treatment analysis).
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Ezetimibe Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description:
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 118 123
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-17.1  (2.0) -52.2  (2.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe, Alirocumab 75 mg/ up to 150 mg
Comments 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 5% level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -35.1
Confidence Interval (2-Sided) 95%
-40.7 to -29.5
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percent Change From Baseline in Calculated LDL--C at Week 12 -- ITT Analysis
Hide Description 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.
Time Frame From Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Ezetimibe Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description:
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 122 126
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-15.6  (2.0) -47.0  (1.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe, Alirocumab 75 mg/ up to 150 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -31.5
Confidence Interval (2-Sided) 95%
-36.9 to -26.1
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 12 - On--Treatment Analysis
Hide Description 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, whichever came first) (on-treatment analysis).
Time Frame From Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Ezetimibe Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description:
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 118 123
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-18.0  (1.8) -51.2  (1.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe, Alirocumab 75 mg/ up to 150 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -33.1
Confidence Interval (2-Sided) 95%
-38.0 to -28.2
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 -- ITT Analysis
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline Apo B value on- or off-treatment.
Arm/Group Title Ezetimibe Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description:
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 116 122
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-11.2  (1.7) -36.3  (1.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe, Alirocumab 75 mg/ up to 150 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -25.1
Confidence Interval (2-Sided) 95%
-29.8 to -20.4
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percent Change From Baseline in Apo B at Week 24 -- On--Treatment Analysis
Hide Description 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, whichever came first).
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed: participants of the mITT population with one baseline and at least one post-baseline Apo B value on-treatment.
Arm/Group Title Ezetimibe Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description:
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 95 109
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-14.4  (1.4) -42.6  (1.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe, Alirocumab 75 mg/ up to 150 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -28.2
Confidence Interval (2-Sided) 95%
-32.1 to -24.4
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percent Change From Baseline in Non--High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 -- ITT Analysis
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Ezetimibe Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description:
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 122 126
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-14.6  (1.7) -40.2  (1.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe, Alirocumab 75 mg/ up to 150 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -25.6
Confidence Interval (2-Sided) 95%
-30.4 to -20.8
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Percent Change From Baseline in Non--HDL-C at Week 24 -- On--Treatment Analysis
Hide Description 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, whichever came first).
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed: participants of the mITT population with one baseline and at least one post-baseline Non-HDL-C value on-treatment.
Arm/Group Title Ezetimibe Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description:
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 118 123
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-17.1  (1.5) -46.9  (1.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe, Alirocumab 75 mg/ up to 150 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -29.8
Confidence Interval (2-Sided) 95%
-33.9 to -25.8
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Percent Change From Baseline in Total Cholesterol (Total--C) at Week 24 - ITT Analysis
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline total-C value on- or off-treatment.
Arm/Group Title Ezetimibe Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description:
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 122 126
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-10.9  (1.4) -31.8  (1.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe, Alirocumab 75 mg/ up to 150 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -20.8
Confidence Interval (2-Sided) 95%
-24.7 to -17.0
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Percent Change From Baseline in Apo B at Week 12 -- ITT Analysis
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Apo B ITT population.
Arm/Group Title Ezetimibe Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description:
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 116 122
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-11.6  (1.5) -36.1  (1.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe, Alirocumab 75 mg/ up to 150 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -24.5
Confidence Interval (2-Sided) 95%
-28.7 to -20.4
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Non-HDL-C ITT population.
Arm/Group Title Ezetimibe Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description:
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 122 126
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-15.8  (1.5) -41.5  (1.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe, Alirocumab 75 mg/ up to 150 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -25.7
Confidence Interval (2-Sided) 95%
-29.9 to -21.5
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Percent Change From Baseline in Total-C at Week 12 - ITT Analysis
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Total-C ITT population.
Arm/Group Title Ezetimibe Alirocumab 75/ up to 150
Hide Arm/Group Description:
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 122 126
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-11.6  (1.2) -32.7  (1.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe, Alirocumab 75/ up to 150
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -21.1
Confidence Interval (2-Sided) 95%
-24.5 to -17.7
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Ezetimibe Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description:
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 122 126
Measure Type: Number
Unit of Measure: percentage of participants
4.4 41.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe, Alirocumab 75 mg/ up to 150 mg
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 19.5
Confidence Interval (2-Sided) 95%
6.9 to 55.2
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis
Hide Description 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, whichever came first (on-treatment analysis).
Time Frame Up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Ezetimibe Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description:
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 118 123
Measure Type: Number
Unit of Measure: percentage of participants
5.6 51.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe, Alirocumab 75 mg/ up to 150 mg
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 24.9
Confidence Interval (2-Sided) 95%
8.6 to 71.9
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Ezetimibe Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description:
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 122 126
Measure Type: Number
Unit of Measure: percentage of participants
0.8 32.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe, Alirocumab 75 mg/ up to 150 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant). Statistical analysis used a last observation carried forward (LOCF) approach followed by Exact conditional logistic regression model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Regression, Exact Conditional Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 71.5
Confidence Interval (2-Sided) 95%
11.1 to 3022.1
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis
Hide Description 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, whichever came first (on-treatment analysis).
Time Frame Up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Ezetimibe Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description:
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 118 123
Measure Type: Number
Unit of Measure: percentage of participants
0.8 39.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe, Alirocumab 75 mg/ up to 150 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant). Statistical analysis used a LOCF approach followed by Exact conditional logistic regression model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Regression, Exact Conditional Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 109.8
Confidence Interval (2-Sided) 95%
16.5 to 4759.3
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis
Hide Description Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed: participants of the ITT population.
Arm/Group Title Ezetimibe Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description:
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 122 126
Mean (Standard Error)
Unit of Measure: percent change
-7.3  (2.5) -25.9  (2.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe, Alirocumab 75 mg/ up to 150 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant). Statistical analysis used a multiple imputation approach followed by a robust regression model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Regression, Robust
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -18.7
Confidence Interval (2-Sided) 95%
-25.5 to -11.8
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline HDL-C value on- or off-treatment.
Arm/Group Title Ezetimibe Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description:
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 122 126
Least Squares Mean (Standard Error)
Unit of Measure: percent change
6.8  (1.7) 7.7  (1.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe, Alirocumab 75 mg/ up to 150 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.6997
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.9
Confidence Interval (2-Sided) 95%
-3.8 to 5.6
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
Hide Description Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed: participants of the ITT population
Arm/Group Title Ezetimibe Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description:
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 122 126
Mean (Standard Error)
Unit of Measure: percent change
-3.6  (2.8) -9.3  (2.7)
20.Secondary Outcome
Title Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Ezetimibe Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description:
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 116 122
Least Squares Mean (Standard Error)
Unit of Measure: percent change
2.9  (1.2) 4.8  (1.2)
21.Secondary Outcome
Title Percent Change From Baseline in Lipoprotein(a) at Week 12 -- ITT Analysis
Hide Description Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression 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
Hide Outcome Measure Data
Hide Analysis Population Description
Lipoprotein(a) ITT population.
Arm/Group Title Ezetimibe Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description:
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 122 126
Mean (Standard Error)
Unit of Measure: percent change
-4.5  (2.3) -21.7  (2.2)
22.Secondary Outcome
Title Percent Change in HDL-C From Baseline to Week 12 -- ITT Analysis
Hide Description Least-squares (LS) means and standard errors (SE) taken from MMRM (mixed-effect model with repeated measures) analysis
Time Frame From Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
HDL-C ITT population.
Arm/Group Title Ezetimibe Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description:
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 122 126
Least Squares Mean (Standard Error)
Unit of Measure: percent change
7.6  (1.2) 9.0  (1.2)
23.Secondary Outcome
Title Percent Change in Fasting Triglycerides From Baseline to Week 12 -- ITT Analysis
Hide Description Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression 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
Hide Outcome Measure Data
Hide Analysis Population Description
Fasting Triglycerides ITT population.
Arm/Group Title Ezetimibe Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description:
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 122 126
Mean (Standard Error)
Unit of Measure: percent change
-9.4  (2.6) -8.0  (2.5)
24.Secondary Outcome
Title Percent Change From Baseline in Apo A--1 at Week 12 -- ITT Analysis
Hide Description Least squares (LS) means and standard errors (SE) taken from MMRM (mixed effect model with repeated measures) analysis.
Time Frame From Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Apo A-1 ITT population.
Arm/Group Title Ezetimibe Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description:
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 116 122
Least Squares Mean (Standard Error)
Unit of Measure: percent change
3.9  (1.0) 5.5  (1.0)
25.Other Pre-specified Outcome
Title Percentage of Participants Who Experienced Skeletal Muscle-related Adverse Event (AE)
Hide Description Skeletal muscle-related adverse events were a predefined category including myalgia, muscle spasms, muscular weakness, musculoskeletal stiffness and muscle fatigue. Events that developed during treatment emergent adverse events period (the time from the first double-blindstudy treatment [injection or capsules, whichever came first] up to the day of the last double-blind injection + 70 days ) are reported.
Time Frame From Baseline up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Atorvastatin (Statin Rechallenge Arm) Ezetimibe (Active Comparator) Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description:
Atorvastatin 20 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 63 124 126
Measure Type: Number
Unit of Measure: participants
Any skeletal muscle-related AE 46.0 41.1 32.5
Leading to treatment discontinuation 22.2 20.2 15.9
26.Other Pre-specified Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 24 Versus Atorvastatin - Raw Data Description - Intent-To-Treat (ITT) Analysis
Hide Description [Not Specified]
Time Frame From Baseline up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Atorvastatin (Statin Rechallenge Arm) Ezetimibe (Active Comparator) Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description:
Atorvastatin 20 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
Overall Number of Participants Analyzed 54 106 112
Mean (Standard Deviation)
Unit of Measure: percent change
-31.9  (25.1) -15.2  (22.4) -47.3  (22.7)
Time Frame From Baseline up to the Last Double-Blind Injection Date + 70 Days
Adverse Event Reporting Description Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment [injection or capsules, whichever came first] up to the day of the last double-blind injection + 70 days ) are reported.
 
Arm/Group Title Atorvastatin Ezetimibe Alirocumab 75 mg/ up to 150 mg
Hide Arm/Group Description Atorvastatin 20 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 22 weeks added to stable LMT. Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo for alirocumab SC injection Q2W for 22 weeks added to stable LMT. Alirocumab 75 mg SC injection Q2W for 22 weeks and placebo for atorvastatin/ezetimibe over-encapsulated tablets orally QD for 24 weeks added to stable LMT. 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 cardiovascular risk.
All-Cause Mortality
Atorvastatin Ezetimibe Alirocumab 75 mg/ up to 150 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Hide Serious Adverse Events
Atorvastatin Ezetimibe Alirocumab 75 mg/ up to 150 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/63 (11.11%)      10/124 (8.06%)      12/126 (9.52%)    
Cardiac disorders       
Acute myocardial infarction  1  0/63 (0.00%)  0/124 (0.00%)  1/126 (0.79%) 
Angina unstable  1  1/63 (1.59%)  0/124 (0.00%)  1/126 (0.79%) 
Aortic valve incompetence  1  0/63 (0.00%)  1/124 (0.81%)  0/126 (0.00%) 
Atrial fibrillation  1  0/63 (0.00%)  1/124 (0.81%)  1/126 (0.79%) 
Cardiovascular disorder  1  0/63 (0.00%)  1/124 (0.81%)  0/126 (0.00%) 
Coronary artery disease  1  0/63 (0.00%)  0/124 (0.00%)  1/126 (0.79%) 
Gastrointestinal disorders       
Nausea  1  1/63 (1.59%)  0/124 (0.00%)  0/126 (0.00%) 
Peritoneal haemorrhage  1  0/63 (0.00%)  0/124 (0.00%)  1/126 (0.79%) 
Small intestinal obstruction  1  1/63 (1.59%)  0/124 (0.00%)  0/126 (0.00%) 
Vomiting  1  1/63 (1.59%)  0/124 (0.00%)  0/126 (0.00%) 
General disorders       
Non-Cardiac chest pain  1  1/63 (1.59%)  4/124 (3.23%)  0/126 (0.00%) 
Immune system disorders       
Hypersensitivity  1  0/63 (0.00%)  1/124 (0.81%)  0/126 (0.00%) 
Infections and infestations       
Appendicitis  1  0/63 (0.00%)  0/124 (0.00%)  1/126 (0.79%) 
Pyelonephritis  1  0/63 (0.00%)  1/124 (0.81%)  0/126 (0.00%) 
Wound infection  1  0/63 (0.00%)  0/124 (0.00%)  1/126 (0.79%) 
Injury, poisoning and procedural complications       
Hip fracture  1  0/63 (0.00%)  0/124 (0.00%)  1/126 (0.79%) 
Post procedural haematoma  1  0/63 (0.00%)  0/124 (0.00%)  1/126 (0.79%) 
Traumatic arthritis  1  0/63 (0.00%)  0/124 (0.00%)  1/126 (0.79%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  0/63 (0.00%)  0/124 (0.00%)  1/126 (0.79%) 
Haemarthrosis  1  0/63 (0.00%)  0/124 (0.00%)  1/126 (0.79%) 
Osteoarthritis  1  1/63 (1.59%)  0/124 (0.00%)  0/126 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Clear cell renal cell carcinoma  1  0/63 (0.00%)  0/124 (0.00%)  1/126 (0.79%) 
Colon cancer  1  1/63 (1.59%)  0/124 (0.00%)  0/126 (0.00%) 
Malignant melanoma  1  0/63 (0.00%)  0/124 (0.00%)  1/126 (0.79%) 
Ovarian epithelial cancer  1  1/63 (1.59%)  0/124 (0.00%)  0/126 (0.00%) 
Nervous system disorders       
Loss of consciousness  1  0/63 (0.00%)  0/124 (0.00%)  1/126 (0.79%) 
Transient ischaemic attack  1  1/63 (1.59%)  0/124 (0.00%)  0/126 (0.00%) 
Psychiatric disorders       
Depression  1  0/63 (0.00%)  0/124 (0.00%)  1/126 (0.79%) 
Vascular disorders       
Aortic aneurysm  1  1/63 (1.59%)  0/124 (0.00%)  0/126 (0.00%) 
Hypertensive crisis  1  0/63 (0.00%)  1/124 (0.81%)  0/126 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, meddra (17.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Atorvastatin Ezetimibe Alirocumab 75 mg/ up to 150 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   35/63 (55.56%)      63/124 (50.81%)      57/126 (45.24%)    
Gastrointestinal disorders       
Diarrhoea  1  3/63 (4.76%)  10/124 (8.06%)  7/126 (5.56%) 
General disorders       
Fatigue  1  5/63 (7.94%)  4/124 (3.23%)  6/126 (4.76%) 
Infections and infestations       
Nasopharyngitis  1  2/63 (3.17%)  10/124 (8.06%)  8/126 (6.35%) 
Upper respiratory tract infection  1  2/63 (3.17%)  5/124 (4.03%)  7/126 (5.56%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  5/63 (7.94%)  9/124 (7.26%)  6/126 (4.76%) 
Back pain  1  5/63 (7.94%)  7/124 (5.65%)  5/126 (3.97%) 
Muscle spasms  1  7/63 (11.11%)  9/124 (7.26%)  5/126 (3.97%) 
Muscular weakness  1  4/63 (6.35%)  4 2/124 (1.61%)  2 1/126 (0.79%)  1
Myalgia  1  17/63 (26.98%)  29/124 (23.39%)  31/126 (24.60%) 
Nervous system disorders       
Headache  1  6/63 (9.52%)  7/124 (5.65%)  6/126 (4.76%) 
Paraesthesia  1  4/63 (6.35%)  0/124 (0.00%)  4/126 (3.17%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, meddra (17.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Not less than 45 days prior to submission for publication or presentation, the Institution shall, or cause the Principal Investigator to, provide the Sponsor with a copy of the Manuscript. The Institution shall consider in good faith any comments from the Sponsor regarding the content, and shall delete Confidential Information upon written request of the Sponsor. At the Sponsor's request, the Institution shall delay publication for an additional 60 days to allow patent applications to be filed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Trial Management
Organization: Regeneron Pharmaceuticals, Inc
EMail: clinicaltrials@regeneron.com
Layout table for additonal information
Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01709513    
Other Study ID Numbers: R727-CL-1119
First Submitted: October 8, 2012
First Posted: October 18, 2012
Results First Submitted: July 29, 2015
Results First Posted: August 28, 2015
Last Update Posted: August 28, 2017