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Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Ezetimibe in Patients With Hypercholesterolemia (ODYSSEY MONO)

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ClinicalTrials.gov Identifier: NCT01644474
Recruitment Status : Completed
First Posted : July 19, 2012
Results First Posted : November 6, 2015
Last Update Posted : November 6, 2015
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: Ezetimibe
Drug: Placebo (for Alirocumab)
Drug: Placebo (for Ezetimibe)
Enrollment 103
Recruitment Details The study was conducted at 8 centers in 4 countries. A total of 204 participants were screened between July 2012 and November 2012, 101 of whom were screen failures. Screen failures were mainly due to exclusion criteria met.
Pre-assignment Details Randomization was stratified according to the diabetes mellitus status. Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 1:1 ratio ( alirocumab:ezetimibe) after confirmation of selection criteria. 103 participants were randomized.
Arm/Group Title Ezetimibe 10 mg Alirocumab 75/Up to 150 mg Q2W
Hide Arm/Group Description Oral ezetimibe 10 mg capsule daily and subcutaneous (SC) placebo injection for alirocumab every 2 weeks (Q2W) for 24 weeks. SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when low density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Period Title: Overall Study
Started 51 [1] 52 [1]
Treated 51 52
Completed 44 44
Not Completed 7 8
Reason Not Completed
Poor compliance to protocol             1             0
Consent withdrawn by participant             0             1
Participant moved             0             1
Adverse Event             4             5
Site scheduling error             1             1
Protocol Violation             1             0
[1]
Randomized
Arm/Group Title Ezetimibe 10 mg Alirocumab 75/Up to 150 mg Q2W Total
Hide Arm/Group Description Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks. SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8. Total of all reporting groups
Overall Number of Baseline Participants 51 52 103
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 51 participants 52 participants 103 participants
59.6  (5.3) 60.8  (4.6) 60.2  (5.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 52 participants 103 participants
Female
24
  47.1%
24
  46.2%
48
  46.6%
Male
27
  52.9%
28
  53.8%
55
  53.4%
Calculated LDL-C in mmol/L   [1] 
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 51 participants 52 participants 103 participants
3.58  (0.6) 3.65  (0.7) 3.62  (0.7)
[1]
Measure Description: Calculated LDL-C in mmol/L from Friedewald formula (LDL cholesterol = Total cholesterol - HDL cholesterol - [Triglyceride/2.2]).
Calculated LDL-C in mg/dL   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 51 participants 52 participants 103 participants
138.3  (24.5) 141.1  (27.1) 139.7  (25.8)
[1]
Measure Description: Calculated LDL-C in mg/dL from Friedewald formula (LDL cholesterol = Total cholesterol - HDL cholesterol - [Triglyceride/5]).
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 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 10 mg Alirocumab 75/Up to 150 mg Q2W
Hide Arm/Group Description:
Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.
SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 51 52
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-15.6  (3.1) -47.2  (3.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg, Alirocumab 75/Up to 150 mg Q2W
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 -31.6
Confidence Interval (2-Sided) 95%
-40.2 to -23.0
Estimation Comments Alirocumab vs Ezetimibe
2.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 MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on­ or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Ezetimibe 10 mg Alirocumab 75/Up to 150 mg Q2W
Hide Arm/Group Description:
Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.
SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 51 52
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-19.6  (2.6) -48.1  (2.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg, Alirocumab 75/Up to 150 mg Q2W
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 -28.5
Confidence Interval (2-Sided) 95%
-35.7 to -21.2
Estimation Comments Alirocumab vs Ezetimibe
3.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 24 regardless of status on­ or off-treatment.
Time Frame From Baseline to Week 24
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 Ezetimibe 10 mg Alirocumab 75/Up to 150 mg Q2W
Hide Arm/Group Description:
Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.
SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 46 48
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-11.0  (2.4) -36.7  (2.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg, Alirocumab 75/Up to 150 mg Q2W
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 -25.8
Confidence Interval (2-Sided) 95%
-32.3 to -19.2
Estimation Comments Alirocumab vs Ezetimibe
4.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 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 Ezetimibe 10 mg Alirocumab 75/Up to 150 mg Q2W
Hide Arm/Group Description:
Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.
SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 51 52
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-15.1  (2.9) -40.6  (2.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg, Alirocumab 75/Up to 150 mg Q2W
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 -25.5
Confidence Interval (2-Sided) 95%
-33.5 to -17.4
Estimation Comments Alirocumab vs Ezetimibe
5.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 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 Ezetimibe 10 mg Alirocumab 75/Up to 150 mg Q2W
Hide Arm/Group Description:
Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.
SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 51 52
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-10.9  (2.2) -29.6  (2.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg, Alirocumab 75/Up to 150 mg Q2W
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 -18.7
Confidence Interval (2-Sided) 95%
-24.7 to -12.7
Estimation Comments Alirocumab vs Ezetimibe
6.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 24
Hide Outcome Measure Data
Hide Analysis Population Description
Apo-B ITT population.
Arm/Group Title Ezetimibe 10 mg Alirocumab 75/Up to 150 mg Q2W
Hide Arm/Group Description:
Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.
SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 46 48
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-11.7  (2.1) -37.3  (2.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg, Alirocumab 75/Up to 150 mg Q2W
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 -25.7
Confidence Interval (2-Sided) 95%
-31.5 to -19.8
Estimation Comments Alirocumab vs Ezetimibe
7.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 24
Hide Outcome Measure Data
Hide Analysis Population Description
non-HDL-C ITT population.
Arm/Group Title Ezetimibe 10 mg Alirocumab 75/Up to 150 mg Q2W
Hide Arm/Group Description:
Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.
SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 51 52
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-16.7  (2.4) -42.5  (2.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg, Alirocumab 75/Up to 150 mg Q2W
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 -25.8
Confidence Interval (2-Sided) 95%
-32.4 to -19.2
Estimation Comments Alirocumab vs Ezetimibe
8.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 24
Hide Outcome Measure Data
Hide Analysis Population Description
Total-C ITT population.
Arm/Group Title Ezetimibe 10 mg Alirocumab 75/Up to 150 mg Q2W
Hide Arm/Group Description:
Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.
SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 51 52
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-12.0  (1.7) -30.3  (1.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg, Alirocumab 75/Up to 150 mg Q2W
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 -18.3
Confidence Interval (2-Sided) 95%
-23.1 to -13.5
Estimation Comments Alirocumab vs Ezetimibe
9.Secondary Outcome
Title Percentage of Participants Achieving 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 multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on­ or off-treatment were included in the imputation model.
Time Frame Up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Ezetimibe 10 mg Alirocumab 75/Up to 150 mg Q2W
Hide Arm/Group Description:
Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.
SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 51 52
Measure Type: Number
Unit of Measure: percentage of participants
32.2 88.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg, Alirocumab 75/Up to 150 mg Q2W
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 34.8
Confidence Interval (2-Sided) 95%
8.7 to 139.0
Estimation Comments Alirocumab vs Ezetimibe
10.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 from multiple imputation approach model including all available post-baseline data from Week 4 to Week 24 regardless of status on­ or off-treatment.
Time Frame Up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Ezetimibe 10 mg Alirocumab 75/Up to 150 mg Q2W
Hide Arm/Group Description:
Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.
SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 51 52
Measure Type: Number
Unit of Measure: percentage of participants
2.4 59.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg, Alirocumab 75/Up to 150 mg Q2W
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 was ≤ 0.05.
Method Regression, Logistic
Comments Multiple imputation approach followed by logistic regression model.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 69.8
Confidence Interval (2-Sided) 95%
8.8 to 556.0
Estimation Comments Alirocumab vs Ezetimibe
11.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 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on­ or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Ezetimibe 10 mg Alirocumab 75/Up to 150 mg Q2W
Hide Arm/Group Description:
Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.
SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 51 52
Mean (Standard Error)
Unit of Measure: percent change
-12.3  (3.8) -16.7  (3.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg, Alirocumab 75/Up to 150 mg Q2W
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 0.4013
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 -4.4
Confidence Interval (2-Sided) 95%
-14.8 to 5.9
Estimation Comments Alirocumab vs Ezetimibe
12.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 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 Ezetimibe 10 mg Alirocumab 75/Up to 150 mg Q2W
Hide Arm/Group Description:
Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.
SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 51 52
Least Squares Mean (Standard Error)
Unit of Measure: percent change
1.6  (1.9) 6.0  (1.9)
13.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 24 regardless of status on­ or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
HDL-C ITT population.
Arm/Group Title Ezetimibe 10 mg Alirocumab 75/Up to 150 mg Q2W
Hide Arm/Group Description:
Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.
SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 51 52
Least Squares Mean (Standard Error)
Unit of Measure: percent change
1.6  (2.0) 9.0  (2.0)
14.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 24 regardless of status on­ or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Ezetimibe 10 mg Alirocumab 75/Up to 150 mg Q2W
Hide Arm/Group Description:
Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.
SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 51 52
Mean (Standard Error)
Unit of Measure: percent change
-14.2  (3.7) -17.2  (3.7)
15.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 24 regardless of status on­ or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Ezetimibe 10 mg Alirocumab 75/Up to 150 mg Q2W
Hide Arm/Group Description:
Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.
SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 51 52
Mean (Standard Error)
Unit of Measure: percent change
-10.8  (4.3) -11.9  (4.2)
16.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 24 regardless of status on­ or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Ezetimibe 10 mg Alirocumab 75/Up to 150 mg Q2W
Hide Arm/Group Description:
Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.
SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 51 52
Mean (Standard Error)
Unit of Measure: percent change
-2.3  (3.5) -12.2  (3.4)
17.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 24 regardless of status on­ or off-treatment.
Time Frame From Baseline to Week 24
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 Ezetimibe 10 mg Alirocumab 75/Up to 150 mg Q2W
Hide Arm/Group Description:
Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.
SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 46 48
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-0.6  (1.6) 4.7  (1.6)
18.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 24 regardless of status on­ or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Apo A-1 ITT population.
Arm/Group Title Ezetimibe 10 mg Alirocumab 75/Up to 150 mg Q2W
Hide Arm/Group Description:
Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.
SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 46 48
Mean (Standard Error)
Unit of Measure: percent change
-2.2  (1.4) 2.3  (1.4)
Time Frame All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to study drug.
Adverse Event Reporting Description Reported adverse events are treatment-emergent adverse events 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 to the day of the last double-blind injection + 70 days).
 
Arm/Group Title Ezetimibe 10 mg Alirocumab 75/Up150 mg Q2W
Hide Arm/Group Description Participants exposed to Ezetimibe 10 mg (mean exposure of 22 weeks). Participants exposed to Alirocumab 75 mg/Up to 150 mg Q2W (mean exposure of 22 weeks).
All-Cause Mortality
Ezetimibe 10 mg Alirocumab 75/Up150 mg Q2W
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Ezetimibe 10 mg Alirocumab 75/Up150 mg Q2W
Affected / at Risk (%) Affected / at Risk (%)
Total   1/51 (1.96%)   1/52 (1.92%) 
Musculoskeletal and connective tissue disorders     
Bone erosion  1  1/51 (1.96%)  0/52 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism  1  0/51 (0.00%)  1/52 (1.92%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDra 16.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ezetimibe 10 mg Alirocumab 75/Up150 mg Q2W
Affected / at Risk (%) Affected / at Risk (%)
Total   27/51 (52.94%)   25/52 (48.08%) 
Gastrointestinal disorders     
Diarrhoea  1  2/51 (3.92%)  6/52 (11.54%) 
Nausea  1  3/51 (5.88%)  3/52 (5.77%) 
Infections and infestations     
Nasopharyngitis  1  8/51 (15.69%)  12/52 (23.08%) 
Influenza  1  3/51 (5.88%)  6/52 (11.54%) 
Upper respiratory tract infection  1  5/51 (9.80%)  2/52 (3.85%) 
Urinary tract infection  1  3/51 (5.88%)  0/52 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  2/51 (3.92%)  3/52 (5.77%) 
Back pain  1  3/51 (5.88%)  1/52 (1.92%) 
Nervous system disorders     
Headache  1  2/51 (3.92%)  3/52 (5.77%) 
Dizziness  1  3/51 (5.88%)  1/52 (1.92%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDra 16.0
Due to administrative error in the automated process (which was detected after database lock), planned dose up­titration criteria for LDL­C levels was changed from ≥100 mg/dL to ≥70 mg/dL.
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: NCT01644474     History of Changes
Other Study ID Numbers: EFC11716
U1111-1124-1167 ( Other Identifier: UTN )
2011-001424-38 ( EudraCT Number )
First Submitted: July 17, 2012
First Posted: July 19, 2012
Results First Submitted: August 20, 2015
Results First Posted: November 6, 2015
Last Update Posted: November 6, 2015