Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    efc11569
Previous Study | Return to List | Next Study

Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Ezetimibe on Top of Statin in High Cardiovascular Risk Patients With Hypercholesterolemia (ODYSSEY COMBO II)

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: NCT01644188
Recruitment Status : Completed
First Posted : July 18, 2012
Results First Posted : November 6, 2015
Last Update Posted : August 4, 2016
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

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: Alirocumab
Drug: Placebo (for alirocumab)
Drug: Ezetimibe
Drug: Placebo (for ezetimibe)
Drug: Lipid Modifying Therapy (LMT)
Enrollment 720
Recruitment Details The study was conducted at 126 centers in 10 countries. Overall, 1112 participants were screened between August 2012 and May 2013, 392 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, intensity of statin treatment and geographical region. Assignment to arms was done centrally using Interactive Voice/Web Response System in 2:1 ratio (alirocumab: ezetimibe) after confirmation of selection criteria. 720 participants were randomized.
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description Subcutaneous injection of alirocumab 75 mg every 2 weeks (Q2W) and oral placebo capsule for ezetimibe daily added to stable Lipid­ Modifying Therapy (LMT) for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when low density lipoprotein cholesterol (LDL-C) level ≥70 mg/dL (1.81 mmol/L) at Week 8. Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Period Title: Overall Study
Started 479 [1] 241 [1]
Treated 479 241
Completed 357 166
Not Completed 122 75
Reason Not Completed
Adverse Event             44             20
Poor compliance to protocol             26             14
Physician Decision             1             3
Participant moved             7             2
Related to auto-injector administration             2             2
Consent withdrawn by participant             14             7
Selection criteria finally not met             2             0
Lost to Follow-up             1             0
Death             4             3
Last visit outside protocol visit window             14             16
Site closure             1             1
Other than specified above             6             7
[1]
Randomized
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg Total
Hide Arm/Group Description Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8. Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks. Total of all reporting groups
Overall Number of Baseline Participants 479 241 720
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 479 participants 241 participants 720 participants
61.7  (9.4) 61.3  (9.2) 61.6  (9.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 479 participants 241 participants 720 participants
Female
119
  24.8%
71
  29.5%
190
  26.4%
Male
360
  75.2%
170
  70.5%
530
  73.6%
Calculated LDL-C in mg/dL   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 479 participants 241 participants 720 participants
108.6  (36.5) 104.6  (34.1) 107.3  (35.7)
[1]
Measure Description: Calculated LDL-C in mg/dL from Friedewald formula (LDL cholesterol = Total cholesterol - HDL cholesterol - [Triglyceride/5]).
Calculated LDL-C in mmol/L  
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 479 participants 241 participants 720 participants
2.812  (0.945) 2.710  (0.884) 2.778  (0.926)
1.Primary Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-treat (ITT) Analysis
Hide Description 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 52 regardless of status on- or off-treatment were used in the model (ITT analysis).
Time Frame From Baseline to Week 52
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 Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 467 240
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-50.6  (1.4) -20.7  (1.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 /up to 150 mg Q2W, Ezetimibe 10 mg
Comments Alirocumab group was compared to ezetimibe 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 -29.8
Confidence Interval (2-Sided) 95%
-34.4 to -25.3
Estimation Comments Alirocumab vs. ezetimibe
2.Secondary Outcome
Title Percent Change From Baseline in Calculated LDL­-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 52 (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 52
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT population (mITT): all randomized and treated participants with one baseline and at least one post-baseline calculated LDL-C value on-treatment.
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 464 235
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-52.4  (1.3) -21.8  (1.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 /up to 150 mg Q2W, Ezetimibe 10 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 0.05 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 -30.6
Confidence Interval (2-Sided) 95%
-34.9 to -26.2
Estimation Comments Alirocumab vs. ezetimibe
3.Secondary Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 12 from a MMRM including all available post-baseline data from week 4 to week 52 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 467 240
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-51.2  (1.3) -21.8  (1.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 /up to 150 mg Q2W, Ezetimibe 10 mg
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was 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 -29.4
Confidence Interval (2-Sided) 95%
-33.7 to -25.1
Estimation Comments Alirocumab vs. ezetimibe
4.Secondary Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
Hide Description Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (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 52
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 464 235
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-52.4  (1.2) -22.7  (1.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 /up to 150 mg Q2W, Ezetimibe 10 mg
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was 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 -29.7
Confidence Interval (2-Sided) 95%
-33.8 to -25.6
Estimation Comments Alirocumab vs. ezetimibe
5.Secondary Outcome
Title Percent Change From Baseline in Apolipoprotein B (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 52 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Participants of the ITT population with one baseline and at least one post-baseline Apo-B value on-or off-treatment (Apo-B ITT population).
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 452 228
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-40.7  (1.1) -18.3  (1.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 /up to 150 mg Q2W, Ezetimibe 10 mg
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was 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 -22.4
Confidence Interval (2-Sided) 95%
-26 to -18.8
Estimation Comments Alirocumab vs. ezetimibe
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 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (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 52
Hide Outcome Measure Data
Hide Analysis Population Description
Participants of the mITT population with one baseline and at least one post-baseline Apo B value on-treatment (Apo-B mITT population).
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 442 221
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-42.1  (1) -19.1  (1.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 /up to 150 mg Q2W, Ezetimibe 10 mg
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was 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 -23
Confidence Interval (2-Sided) 95%
-26.5 to -19.6
Estimation Comments Alirocumab vs. ezetimibe
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 52 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Participants of the ITT population with one baseline and at least one post-baseline non-HDL-C value on- or off-treatment (non-HDL-C ITT population).
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 467 240
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-42.1  (1.2) -19.2  (1.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 /up to 150 mg Q2W, Ezetimibe 10 mg
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was 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 -22.9
Confidence Interval (2-Sided) 95%
-26.9 to -18.9
Estimation Comments Alirocumab vs. ezetimibe
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 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first).
Time Frame From Baseline up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Participants of the mITT population with one baseline and at least one post-baseline non-HDL-C value on-treatment (non-HDL-C mITT population).
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 464 235
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-43.7  (1.1) -20.2  (1.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 /up to 150 mg Q2W, Ezetimibe 10 mg
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was 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 -23.5
Confidence Interval (2-Sided) 95%
-27.2 to -19.7
Estimation Comments Alirocumab vs. ezetimibe
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 52 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Participants of the ITT population with one baseline and at least one post-baseline Total-C value on- or off-treatment (Total-C ITT population).
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 467 240
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-29.3  (0.9) -14.6  (1.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 /up to 150 mg Q2W, Ezetimibe 10 mg
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was 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 -14.7
Confidence Interval (2-Sided) 95%
-17.7 to -11.7
Estimation Comments Alirocumab vs. ezetimibe
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 52 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Apo-B ITT population.
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 452 228
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-39.7  (1) -17.2  (1.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 /up to 150 mg Q2W, Ezetimibe 10 mg
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was 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 -22.5
Confidence Interval (2-Sided) 95%
-25.7 to -19.2
Estimation Comments Alirocumab vs. ezetimibe
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 52 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Non-HDL-C ITT population.
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 467 240
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-42.6  (1.1) -20.6  (1.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 /up to 150 mg Q2W, Ezetimibe 10 mg
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was 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 -22
Confidence Interval (2-Sided) 95%
-25.6 to -18.3
Estimation Comments Alirocumab vs. ezetimibe
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 52 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Total-C ITT population
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 467 240
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-29.4  (0.8) -15.1  (1.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 /up to 150 mg Q2W, Ezetimibe 10 mg
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was 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 -14.3
Confidence Interval (2-Sided) 95%
-17.1 to -11.6
Estimation Comments Alirocumab vs. ezetimibe
13.Secondary Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 52 from a MMRM model including all available post-baseline data from week 4 to week 52 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 467 240
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-49.5  (1.5) -18.3  (2.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 /up to 150 mg Q2W, Ezetimibe 10 mg
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was 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 -31.2
Confidence Interval (2-Sided) 95%
-36.3 to -26.1
Estimation Comments Alirocumab vs. ezetimibe
14.Secondary Outcome
Title Percentage of Participants Achieving 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 multiple imputation approach for handling of missing data. All available post-baseline data from week 4 to week 52 regardless of status on- or off-treatment were included in the imputation model.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 467 240
Measure Type: Number
Unit of Measure: percentage of participants
77 45.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 /up to 150 mg Q2W, Ezetimibe 10 mg
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was 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 Regression, Logistic
Comments Multiple imputation approach followed by Logistic regression model.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.4
Confidence Interval (2-Sided) 95%
3.7 to 7.9
Estimation Comments Alirocumab vs. ezetimibe
15.Secondary Outcome
Title Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis
Hide Description Adjusted percentages at Week 24 from multiple imputation approach including available post-baseline on-treatment data from week 4 to week 52 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first).
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 464 235
Measure Type: Number
Unit of Measure: percentage of participants
78.9 47.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 /up to 150 mg Q2W, Ezetimibe 10 mg
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was 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 Regression, Logistic
Comments Multiple imputation approach followed by logistic regression model
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.9
Confidence Interval (2-Sided) 95%
3.9 to 8.8
Estimation Comments Alirocumab vs. ezetimibe
16.Secondary Outcome
Title Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis
Hide Description Adjusted means and standard errors at Week 24 were obtained from multiple imputation approach followed by robust regression model for handling of missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment were included in the imputation model.
Time Frame From baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 467 240
Mean (Standard Error)
Unit of Measure: percent change
-27.8  (1.4) -6.1  (2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 /up to 150 mg Q2W, Ezetimibe 10 mg
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was 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 Regression, Robust
Comments Multiple imputation approach followed by robust regression model.
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -21.7
Confidence Interval (2-Sided) 95%
-26.4 to -17
Estimation Comments Alirocumab vs. ezetimibe
17.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 52 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Participants of the ITT population with one baseline and at least one post-baseline HDL-C value on- or off-treatment (HDL-C ITT population).
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 467 240
Least Squares Mean (Standard Error)
Unit of Measure: percent change
8.6  (0.8) 0.5  (1.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 /up to 150 mg Q2W, Ezetimibe 10 mg
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was 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 8.1
Confidence Interval (2-Sided) 95%
5.4 to 10.7
Estimation Comments Alirocumab vs. ezetimibe
18.Secondary Outcome
Title Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
Hide Description Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 467 240
Mean (Standard Error)
Unit of Measure: percent change
-13  (1.5) -12.8  (2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 /up to 150 mg Q2W, Ezetimibe 10 mg
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9117
Comments Threshold for significance ≤ 0.05.
Method Regression, Robust
Comments Multiple imputation approach followed by robust regression.
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-5.1 to 4.6
Estimation Comments Alirocumab vs. ezetimibe
19.Secondary Outcome
Title Percent Change From Baseline in Apolipoprotein A-1 (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 52 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Participants of the ITT population with one baseline and at least one post-baseline Apo A-1 value on- or off-treatment (Apo A-1 ITT population).
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 452 228
Least Squares Mean (Standard Error)
Unit of Measure: percent change
5  (0.6) -1.3  (0.8)
20.Secondary Outcome
Title Percent Change From Baseline in Lipoprotein(a) at Week 12 - ITT Analysis
Hide Description Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 467 240
Mean (Standard Error)
Unit of Measure: percent change
-22.1  (1.2) 1.1  (1.7)
21.Secondary Outcome
Title Percent Change From Baseline in 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 52 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
HDL-C ITT population.
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 467 240
Least Squares Mean (Standard Error)
Unit of Measure: percent change
8.7  (0.7) 2.8  (1)
22.Secondary Outcome
Title Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis
Hide Description Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 467 240
Mean (Standard Error)
Unit of Measure: percent change
-13  (1.5) -12.8  (2.0)
23.Secondary Outcome
Title Percent Change From Baseline in Apo A-1 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 52 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Apo A-1 ITT population.
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 467 240
Least Squares Mean (Standard Error)
Unit of Measure: percent change
1.5  (0.5) -2.9  (0.7)
24.Other Pre-specified Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 52 - On-Treatment Analysis
Hide Description Adjusted LS means and standard errors at Week 52 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (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 52
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 464 235
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-51.8  (1.5) -19.7  (2.1)
25.Other Pre-specified Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 104 - ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 104 from MMRM including all available post-baseline data from Week 4 to Week 104 regardless of status on-or off-treatment.
Time Frame From Baseline to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 467 240
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-44.2  (1.7) -15.2  (2.4)
26.Other Pre-specified Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 104 – On-Treatment Analysis
Hide Description Adjusted LS means and standard errors at Week 104 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 104 (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 104
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Alirocumab 75 /up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description:
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily added to stable LMT for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.
Oral ezetimibe 10 mg capsule daily and subcutaneous placebo injection for alirocumab Q2W added to stable LMT for 104 weeks.
Overall Number of Participants Analyzed 464 235
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-48.9  (1.7) -17.0  (2.4)
Time Frame All Adverse Events (AE) were collected from signature of the informed consent form up to final visit (Week 112) in the study regardless of seriousness or relationship to study drugs.
Adverse Event Reporting Description Reported AEs are treatment emergent that is AEs that developed/worsened during 'the treatment emergent period' (from the first dose of double-blind study drug administration [capsule or injection, whichever came first] up the day of the last double blind injection + 70 days).
 
Arm/Group Title Alirocumab 75/Up to 150 mg Q2W Ezetimibe 10 mg
Hide Arm/Group Description Participants exposed to Alirocumab 75 /up to 150 mg Q2W added to stable LMT (mean exposition of 90 weeks). Participants exposed to Ezetimibe 10 mg added to stable LMT (mean exposition of 90 weeks).
All-Cause Mortality
Alirocumab 75/Up to 150 mg Q2W Ezetimibe 10 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Alirocumab 75/Up to 150 mg Q2W Ezetimibe 10 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   124/479 (25.89%)   60/241 (24.90%) 
Blood and lymphatic system disorders     
Anaemia  1  2/479 (0.42%)  2/241 (0.83%) 
Haemorrhagic anaemia  1  1/479 (0.21%)  0/241 (0.00%) 
Cardiac disorders     
Angina pectoris  1  10/479 (2.09%)  6/241 (2.49%) 
Acute myocardial infarction  1  12/479 (2.51%)  3/241 (1.24%) 
Atrial fibrillation  1  4/479 (0.84%)  2/241 (0.83%) 
Angina unstable  1  9/479 (1.88%)  6/241 (2.49%) 
Cardiac failure congestive  1  4/479 (0.84%)  0/241 (0.00%) 
Cardiac arrest  1  4/479 (0.84%)  0/241 (0.00%) 
Atrioventricular block second degree  1  1/479 (0.21%)  2/241 (0.83%) 
Cardiac failure  1  2/479 (0.42%)  2/241 (0.83%) 
Myocardial infarction  1  3/479 (0.63%)  0/241 (0.00%) 
Ventricular tachycardia  1  2/479 (0.42%)  1/241 (0.41%) 
Atrial flutter  1  2/479 (0.42%)  1/241 (0.41%) 
Atrioventricular block  1  1/479 (0.21%)  0/241 (0.00%) 
Atrioventricular block complete  1  2/479 (0.42%)  1/241 (0.41%) 
Supraventricular tachycardia  1  1/479 (0.21%)  0/241 (0.00%) 
Ventricular extrasystoles  1  0/479 (0.00%)  2/241 (0.83%) 
Acute coronary syndrome  1  1/479 (0.21%)  0/241 (0.00%) 
Arrhythmia  1  0/479 (0.00%)  1/241 (0.41%) 
Arteriosclerosis coronary artery  1  1/479 (0.21%)  0/241 (0.00%) 
Cardiogenic shock  1  1/479 (0.21%)  0/241 (0.00%) 
Congestive cardiomyopathy  1  1/479 (0.21%)  0/241 (0.00%) 
Coronary artery disease  1  1/479 (0.21%)  1/241 (0.41%) 
Myocardial ischaemia  1  1/479 (0.21%)  1/241 (0.41%) 
Silent myocardial infarction  1  1/479 (0.21%)  0/241 (0.00%) 
Ventricular fibrillation  1  1/479 (0.21%)  0/241 (0.00%) 
Defect conduction intraventricular  1  0/479 (0.00%)  1/241 (0.41%) 
Ear and labyrinth disorders     
Cupulolithiasis  1  0/479 (0.00%)  1/241 (0.41%) 
Endocrine disorders     
Goitre  1  1/479 (0.21%)  1/241 (0.41%) 
Eye disorders     
Cataract  1  2/479 (0.42%)  0/241 (0.00%) 
Vision blurred  1  0/479 (0.00%)  1/241 (0.41%) 
Retinal detachment  1  1/479 (0.21%)  0/241 (0.00%) 
Ophthalmoplegia  1  1/479 (0.21%)  0/241 (0.00%) 
Cataract nuclear  1  0/479 (0.00%)  1/241 (0.41%) 
Gastrointestinal disorders     
Constipation  1  0/479 (0.00%)  1/241 (0.41%) 
Gastritis  1  1/479 (0.21%)  1/241 (0.41%) 
Inguinal hernia  1  3/479 (0.63%)  0/241 (0.00%) 
Gastrooesophageal reflux disease  1  0/479 (0.00%)  1/241 (0.41%) 
Large intestine polyp  1  2/479 (0.42%)  0/241 (0.00%) 
Abdominal pain  1  0/479 (0.00%)  1/241 (0.41%) 
Haemorrhoids  1  2/479 (0.42%)  0/241 (0.00%) 
Vomiting  1  2/479 (0.42%)  0/241 (0.00%) 
Abdominal distension  1  1/479 (0.21%)  0/241 (0.00%) 
Gastric ulcer haemorrhage  1  3/479 (0.63%)  0/241 (0.00%) 
Abdominal hernia  1  2/479 (0.42%)  0/241 (0.00%) 
Diverticulum intestinal  1  0/479 (0.00%)  1/241 (0.41%) 
Pancreatitis  1  2/479 (0.42%)  0/241 (0.00%) 
Diverticular perforation  1  1/479 (0.21%)  0/241 (0.00%) 
Gastric haemorrhage  1  1/479 (0.21%)  0/241 (0.00%) 
Gastroduodenitis  1  1/479 (0.21%)  0/241 (0.00%) 
Irritable bowel syndrome  1  0/479 (0.00%)  1/241 (0.41%) 
Rectal haemorrhage  1  0/479 (0.00%)  1/241 (0.41%) 
Gastrointestinal haemorrhage  1  0/479 (0.00%)  1/241 (0.41%) 
General disorders     
Non-cardiac chest pain  1  6/479 (1.25%)  2/241 (0.83%) 
Asthenia  1  1/479 (0.21%)  0/241 (0.00%) 
Chest pain  1  2/479 (0.42%)  0/241 (0.00%) 
Implant site haematoma  1  1/479 (0.21%)  0/241 (0.00%) 
Sudden cardiac death  1  1/479 (0.21%)  1/241 (0.41%) 
Sudden death  1  0/479 (0.00%)  1/241 (0.41%) 
Hepatobiliary disorders     
Cholelithiasis  1  1/479 (0.21%)  0/241 (0.00%) 
Cholecystitis acute  1  1/479 (0.21%)  0/241 (0.00%) 
Immune system disorders     
Hypersensitivity  1  1/479 (0.21%)  0/241 (0.00%) 
Infections and infestations     
Bronchitis  1  1/479 (0.21%)  1/241 (0.41%) 
Pneumonia  1  9/479 (1.88%)  1/241 (0.41%) 
Diverticulitis  1  3/479 (0.63%)  0/241 (0.00%) 
Gastroenteritis viral  1  1/479 (0.21%)  0/241 (0.00%) 
Gastroenteritis  1  1/479 (0.21%)  0/241 (0.00%) 
Arthritis infective  1  1/479 (0.21%)  0/241 (0.00%) 
Bronchopneumonia  1  1/479 (0.21%)  0/241 (0.00%) 
Cellulitis of male external genital organ  1  1/479 (0.21%)  0/241 (0.00%) 
Colonic abscess  1  1/479 (0.21%)  0/241 (0.00%) 
Hepatitis E  1  1/479 (0.21%)  0/241 (0.00%) 
Osteomyelitis chronic  1  1/479 (0.21%)  0/241 (0.00%) 
Peritonitis  1  0/479 (0.00%)  1/241 (0.41%) 
Postoperative wound infection  1  1/479 (0.21%)  0/241 (0.00%) 
Pulmonary tuberculosis  1  1/479 (0.21%)  0/241 (0.00%) 
Pyelonephritis acute  1  1/479 (0.21%)  0/241 (0.00%) 
Scrotal abscess  1  1/479 (0.21%)  0/241 (0.00%) 
Staphylococcal bacteraemia  1  1/479 (0.21%)  0/241 (0.00%) 
Urosepsis  1  1/479 (0.21%)  0/241 (0.00%) 
Wound infection  1  1/479 (0.21%)  0/241 (0.00%) 
Myringitis bullous  1  0/479 (0.00%)  1/241 (0.41%) 
Pneumonia staphylococcal  1  0/479 (0.00%)  1/241 (0.41%) 
Injury, poisoning and procedural complications     
Fall  1  1/479 (0.21%)  0/241 (0.00%) 
Contusion  1  1/479 (0.21%)  0/241 (0.00%) 
Rib fracture  1  0/479 (0.00%)  1/241 (0.41%) 
Wound  1  1/479 (0.21%)  0/241 (0.00%) 
Road traffic accident  1  0/479 (0.00%)  1/241 (0.41%) 
Incisional hernia  1  1/479 (0.21%)  0/241 (0.00%) 
Laceration  1  1/479 (0.21%)  0/241 (0.00%) 
Ankle fracture  1  1/479 (0.21%)  0/241 (0.00%) 
Coronary artery restenosis  1  1/479 (0.21%)  1/241 (0.41%) 
Fibula fracture  1  1/479 (0.21%)  0/241 (0.00%) 
Hand fracture  1  1/479 (0.21%)  0/241 (0.00%) 
Hip fracture  1  1/479 (0.21%)  0/241 (0.00%) 
Meniscus injury  1  1/479 (0.21%)  0/241 (0.00%) 
Multiple fractures  1  1/479 (0.21%)  0/241 (0.00%) 
Patella fracture  1  1/479 (0.21%)  0/241 (0.00%) 
Skeletal injury  1  1/479 (0.21%)  0/241 (0.00%) 
Pubis fracture  1  0/479 (0.00%)  1/241 (0.41%) 
Spinal compression fracture  1  0/479 (0.00%)  1/241 (0.41%) 
Investigations     
International normalised ratio increased  1  1/479 (0.21%)  0/241 (0.00%) 
Bacterial test positive  1  1/479 (0.21%)  0/241 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  2/479 (0.42%)  1/241 (0.41%) 
Osteoarthritis  1  3/479 (0.63%)  0/241 (0.00%) 
Rotator cuff syndrome  1  1/479 (0.21%)  0/241 (0.00%) 
Spinal osteoarthritis  1  0/479 (0.00%)  1/241 (0.41%) 
Flank pain  1  0/479 (0.00%)  1/241 (0.41%) 
Spinal column stenosis  1  1/479 (0.21%)  0/241 (0.00%) 
Compartment syndrome  1  0/479 (0.00%)  1/241 (0.41%) 
Spinal instability  1  0/479 (0.00%)  1/241 (0.41%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Prostate cancer  1  3/479 (0.63%)  1/241 (0.41%) 
Pancreatic carcinoma  1  2/479 (0.42%)  0/241 (0.00%) 
Chronic lymphocytic leukaemia  1  1/479 (0.21%)  0/241 (0.00%) 
Lung adenocarcinoma  1  1/479 (0.21%)  0/241 (0.00%) 
Malignant melanoma  1  1/479 (0.21%)  0/241 (0.00%) 
Oesophageal carcinoma  1  1/479 (0.21%)  0/241 (0.00%) 
Oestrogen receptor positive breast cancer  1  1/479 (0.21%)  0/241 (0.00%) 
Pituitary tumour benign  1  1/479 (0.21%)  0/241 (0.00%) 
Renal neoplasm  1  1/479 (0.21%)  0/241 (0.00%) 
Squamous cell carcinoma of lung  1  1/479 (0.21%)  1/241 (0.41%) 
Squamous cell carcinoma of skin  1  0/479 (0.00%)  1/241 (0.41%) 
Gastrointestinal stromal tumour  1  0/479 (0.00%)  1/241 (0.41%) 
Metastases to central nervous system  1  0/479 (0.00%)  1/241 (0.41%) 
Non-small cell lung cancer  1  0/479 (0.00%)  1/241 (0.41%) 
Non-small cell lung cancer metastatic  1  0/479 (0.00%)  1/241 (0.41%) 
Non-small cell lung cancer stage IIIA  1  0/479 (0.00%)  1/241 (0.41%) 
Nervous system disorders     
Dizziness  1  2/479 (0.42%)  0/241 (0.00%) 
Headache  1  1/479 (0.21%)  0/241 (0.00%) 
Paraesthesia  1  0/479 (0.00%)  1/241 (0.41%) 
Ischaemic stroke  1  3/479 (0.63%)  1/241 (0.41%) 
Syncope  1  2/479 (0.42%)  4/241 (1.66%) 
Transient ischaemic attack  1  3/479 (0.63%)  0/241 (0.00%) 
Carotid artery stenosis  1  2/479 (0.42%)  0/241 (0.00%) 
Presyncope  1  1/479 (0.21%)  0/241 (0.00%) 
Brain injury  1  1/479 (0.21%)  0/241 (0.00%) 
Cerebrosclerosis  1  1/479 (0.21%)  0/241 (0.00%) 
Dementia Alzheimer's type  1  1/479 (0.21%)  0/241 (0.00%) 
Facial paresis  1  1/479 (0.21%)  0/241 (0.00%) 
Hypoxic-ischaemic encephalopathy  1  1/479 (0.21%)  0/241 (0.00%) 
Intracranial aneurysm  1  1/479 (0.21%)  0/241 (0.00%) 
Myelitis transverse  1  1/479 (0.21%)  0/241 (0.00%) 
Sensory disturbance  1  1/479 (0.21%)  0/241 (0.00%) 
Carotid artery disease  1  0/479 (0.00%)  1/241 (0.41%) 
Cerebral haemorrhage  1  0/479 (0.00%)  1/241 (0.41%) 
Loss of consciousness  1  0/479 (0.00%)  1/241 (0.41%) 
Transient global amnesia  1  0/479 (0.00%)  1/241 (0.41%) 
Psychiatric disorders     
Anxiety  1  0/479 (0.00%)  1/241 (0.41%) 
Depression  1  0/479 (0.00%)  1/241 (0.41%) 
Confusional state  1  0/479 (0.00%)  1/241 (0.41%) 
Completed suicide  1  0/479 (0.00%)  1/241 (0.41%) 
Renal and urinary disorders     
Haematuria  1  2/479 (0.42%)  0/241 (0.00%) 
Nephrolithiasis  1  1/479 (0.21%)  0/241 (0.00%) 
Acute kidney injury  1  2/479 (0.42%)  2/241 (0.83%) 
Calculus ureteric  1  1/479 (0.21%)  0/241 (0.00%) 
Renal tubular necrosis  1  0/479 (0.00%)  1/241 (0.41%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  1/479 (0.21%)  0/241 (0.00%) 
Chronic obstructive pulmonary disease  1  4/479 (0.84%)  0/241 (0.00%) 
Pleuritic pain  1  1/479 (0.21%)  0/241 (0.00%) 
Sleep apnoea syndrome  1  1/479 (0.21%)  0/241 (0.00%) 
Pneumonia aspiration  1  1/479 (0.21%)  0/241 (0.00%) 
Vocal cord polyp  1  1/479 (0.21%)  0/241 (0.00%) 
Pulmonary embolism  1  0/479 (0.00%)  1/241 (0.41%) 
Pulmonary oedema  1  0/479 (0.00%)  1/241 (0.41%) 
Skin and subcutaneous tissue disorders     
Urticaria  1  0/479 (0.00%)  1/241 (0.41%) 
Eczema nummular  1  1/479 (0.21%)  0/241 (0.00%) 
Vascular disorders     
Hypertension  1  3/479 (0.63%)  1/241 (0.41%) 
Peripheral arterial occlusive disease  1  2/479 (0.42%)  2/241 (0.83%) 
Peripheral vascular disorder  1  1/479 (0.21%)  0/241 (0.00%) 
Aortic dissection  1  1/479 (0.21%)  0/241 (0.00%) 
Femoral artery occlusion  1  1/479 (0.21%)  0/241 (0.00%) 
Thrombophlebitis superficial  1  1/479 (0.21%)  0/241 (0.00%) 
Venous thrombosis limb  1  1/479 (0.21%)  0/241 (0.00%) 
Peripheral artery aneurysm  1  0/479 (0.00%)  1/241 (0.41%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDra 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Alirocumab 75/Up to 150 mg Q2W Ezetimibe 10 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   185/479 (38.62%)   90/241 (37.34%) 
Infections and infestations     
Upper respiratory tract infection  1  42/479 (8.77%)  17/241 (7.05%) 
Nasopharyngitis  1  23/479 (4.80%)  15/241 (6.22%) 
Influenza  1  22/479 (4.59%)  16/241 (6.64%) 
Injury, poisoning and procedural complications     
Accidental overdose  1  47/479 (9.81%)  19/241 (7.88%) 
Musculoskeletal and connective tissue disorders     
Myalgia  1  25/479 (5.22%)  13/241 (5.39%) 
Nervous system disorders     
Dizziness  1  28/479 (5.85%)  18/241 (7.47%) 
Headache  1  29/479 (6.05%)  13/241 (5.39%) 
Vascular disorders     
Hypertension  1  31/479 (6.47%)  14/241 (5.81%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDra 18.0
Manual reclassification was done by the Sponsor for the "other reasons" of non-completion of study as specified in the electronic case report form (eCRF).
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.
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Results Point of Contact
Name/Title: Trial Transparency Team
Organization: Sanofi
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01644188     History of Changes
Other Study ID Numbers: EFC11569
U1111-1121-4315 ( Other Identifier: UTN )
2011-004130-34 ( EudraCT Number )
First Submitted: July 16, 2012
First Posted: July 18, 2012
Results First Submitted: August 20, 2015
Results First Posted: November 6, 2015
Last Update Posted: August 4, 2016