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Efficacy and Safety Evaluation of Alirocumab in Patients With Heterozygous Familial Hypercholesterolemia or High Cardiovascular Risk Patients With Hypercholesterolemia on Lipid Modifying Therapy (ODYSSEY JAPAN)

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ClinicalTrials.gov Identifier: NCT02107898
Recruitment Status : Completed
First Posted : April 8, 2014
Results First Posted : January 29, 2016
Last Update Posted : October 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: Placebo (for alirocumab)
Drug: Alirocumab
Drug: Lipid-Modifying Therapy (LMT)
Enrollment 216
Recruitment Details The study was conducted at 31 centers in Japan. A total of 319 participants were screened between March 2014 and July 2014, 103 of whom were screen failures. Screen failures were mainly due to exclusion criteria met.
Pre-assignment Details Randomization was stratified according to heterozygous familial hypercholesterolemia (heFH) population. Assignment to treatment arms was done using an Interactive Web Response System in 1:2 (Placebo: Alirocumab) ratio after confirmation of selection criteria. 216 participants were randomized.
Arm/Group Title Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description Placebo (for alirocumab) subcutaneous (SC) injection every two weeks (Q2W) added to stable lipid-modifying therapy (LMT) for 52 weeks. Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Period Title: Overall Study
Started 72 [1] 144 [1]
Treated 72 143
Completed 66 132
Not Completed 6 12
Reason Not Completed
Adverse Event             4             7
Poor compliance to protocol             0             1
Participant moved             0             2
Consent withdrawn by participant             2             1
Randomized but not treated             0             1
[1]
Randomized
Arm/Group Title Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W Total
Hide Arm/Group Description Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks. Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012. Total of all reporting groups
Overall Number of Baseline Participants 72 144 216
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 72 participants 144 participants 216 participants
61.8  (9.0) 60.3  (9.7) 60.8  (9.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 72 participants 144 participants 216 participants
Female
25
  34.7%
60
  41.7%
85
  39.4%
Male
47
  65.3%
84
  58.3%
131
  60.6%
Calculated LDL-C in mg/dL   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 72 participants 144 participants 216 participants
141.6  (26.7) 140.9  (26.8) 141.2  (26.7)
[1]
Measure Description: Calculated LDL-C in mg/dL from Friedewald formula (LDL-C = Total cholesterol - High-density lipoprotein cholesterol [HDL-C] - [Triglyceride/5]).
Calculated LDL-C in mmol/L  
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 72 participants 144 participants 216 participants
3.668  (0.691) 3.650  (0.693) 3.656  (0.691)
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 Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Number of Participants Analyzed 72 143
Least Squares Mean (Standard Error)
Unit of Measure: percent change
1.6  (1.8) -62.5  (1.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg/Up to 150 mg Q2W
Comments Alirocumab group was compared to placebo 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 -64.1
Confidence Interval (2-Sided) 95%
-68.5 to -59.8
Estimation Comments Alirocumab vs. Placebo
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 24 (i.e. up to 21 days after last injection) (on-treatment analysis).
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT (mITT) population: all randomized and treated participants with one baseline and at least one post-baseline calculated LDL-C value on-treatment.
Arm/Group Title Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Number of Participants Analyzed 71 143
Least Squares Mean (Standard Error)
Unit of Measure: percent change
1.7  (1.7) -63.7  (1.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg/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 -65.3
Confidence Interval (2-Sided) 95%
-69.4 to -61.3
Estimation Comments Alirocumab vs. Placebo
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 MMRM model including 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 Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Number of Participants Analyzed 72 143
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-2.7  (1.6) -64.2  (1.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg/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 -61.5
Confidence Interval (2-Sided) 95%
-65.3 to -57.7
Estimation Comments Alirocumab vs. Placebo
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 24 (i.e. up to 21 days after last injection).
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Number of Participants Analyzed 71 143
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-2.8  (1.5) -64.8  (1.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg/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 -62.1
Confidence Interval (2-Sided) 95%
-65.8 to -58.3
Estimation Comments Alirocumab vs. Placebo
5.Secondary Outcome
Title Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame From baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants 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 Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Number of Participants Analyzed 71 141
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-1.6  (1.7) -55.0  (1.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg/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 -53.3
Confidence Interval (2-Sided) 95%
-57.5 to -49.1
Estimation Comments Alirocumab vs. Placebo
6.Secondary Outcome
Title Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis
Hide Description Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).
Time Frame From Baseline to Week 24
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 Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Number of Participants Analyzed 70 140
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-2.1  (1.7) -55.9  (1.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg/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 -53.8
Confidence Interval (2-Sided) 95%
-57.8 to -49.8
Estimation Comments Alirocumab vs. Placebo
7.Secondary Outcome
Title Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants 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 Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Number of Participants Analyzed 72 143
Least Squares Mean (Standard Error)
Unit of Measure: percent change
2.6  (1.6) -54.9  (1.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg/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 -57.5
Confidence Interval (2-Sided) 95%
-61.5 to -53.5
Estimation Comments Alirocumab vs. Placebo
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 24 (i.e. up to 21 days after last injection).
Time Frame From Baseline to Week 24
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 Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Number of Participants Analyzed 71 143
Least Squares Mean (Standard Error)
Unit of Measure: percent change
2.6  (1.6) -56.0  (1.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg/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 -58.6
Confidence Interval (2-Sided) 95%
-62.3 to -54.8
Estimation Comments Alirocumab vs. Placebo
9.Secondary Outcome
Title Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants 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 Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Number of Participants Analyzed 72 143
Least Squares Mean (Standard Error)
Unit of Measure: percent change
2.0  (1.3) -39.5  (0.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg/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 -41.5
Confidence Interval (2-Sided) 95%
-44.6 to -38.4
Estimation Comments Alirocumab vs. Placebo
10.Secondary Outcome
Title Percent Change From Baseline in Apo B at Week 12 - ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Apo B ITT population.
Arm/Group Title Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Number of Participants Analyzed 71 141
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-3.3  (1.5) -54.6  (1.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg/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 -51.2
Confidence Interval (2-Sided) 95%
-54.9 to -47.6
Estimation Comments Alirocumab vs. Placebo
11.Secondary Outcome
Title Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Non-HDL-C ITT population.
Arm/Group Title Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Number of Participants Analyzed 72 143
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-1.7  (1.4) -56.3  (1.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg/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 [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -54.5
Confidence Interval (2-Sided) 95%
-57.9 to -51.1
Estimation Comments Alirocumab vs. Placebo
12.Secondary Outcome
Title Percent Change From Baseline in Total-C at Week 12 - ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Total-C ITT population.
Arm/Group Title Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Number of Participants Analyzed 72 143
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-2.1  (1.1) -41.1  (0.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg/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 -39.0
Confidence Interval (2-Sided) 95%
-41.7 to -36.4
Estimation Comments Alirocumab vs. Placebo
13.Secondary Outcome
Title Percentage of Participants Reaching Calculated LDL-C Goal at Week 24 - ITT Analysis
Hide Description

Calculated LDL-C goal was defined as:

  • <100 mg/dL (2.59 mmol/L) for heFH or non-FH participants who had a history of documented congestive heart disease (CHD), or
  • <120 mg/dL (3.10 mmol/L) for non-FH participants who had a history of documented diseases (ischemic stroke, peripheral artery disease, chronic kidney disease or diabetes) or other risk factors as defined in JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.

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 imputation model.

Time Frame Up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Number of Participants Analyzed 72 143
Measure Type: Number
Unit of Measure: percentage of participants
10.2 96.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg/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 552.1
Confidence Interval (2-Sided) 95%
105.6 to 2886.8
Estimation Comments Alirocumab vs. Placebo
14.Secondary Outcome
Title Percentage of Participants Reaching Calculated LDL-C Goal at Week 24 - On-Treatment Analysis
Hide Description Adjusted percentages at Week 24 were from multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).
Time Frame Up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Number of Participants Analyzed 71 143
Measure Type: Number
Unit of Measure: percentage of participants
10.6 97.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg/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 1367.8
Confidence Interval (2-Sided) 95%
137.8 to 13578.3
Estimation Comments Alirocumab vs. Placebo
15.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 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 From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Number of Participants Analyzed 72 143
Mean (Standard Error)
Unit of Measure: percent change
2.5  (2.5) -39.5  (1.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg/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, Robust
Comments Multiple imputation approach followed by a robust regression model.
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -42.0
Confidence Interval (2-Sided) 95%
-48.0 to -36.0
Estimation Comments Alirocumab vs. Placebo
16.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 Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Number of Participants Analyzed 72 143
Mean (Standard Error)
Unit of Measure: percent change
6.7  (3.7) -15.3  (2.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg/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, Robust
Comments Multiple imputation approach followed by a robust regression model.
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -22.0
Confidence Interval (2-Sided) 95%
-30.9 to -13.1
Estimation Comments Alirocumab vs. Placebo
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 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 Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Number of Participants Analyzed 72 143
Least Squares Mean (Standard Error)
Unit of Measure: percent change
2.1  (1.5) 7.9  (1.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg/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 0.0020
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 5.8
Confidence Interval (2-Sided) 95%
2.1 to 9.4
Estimation Comments Alirocumab vs. Placebo
18.Secondary Outcome
Title Percent Change From Baseline in Apo A1 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 A1 value on- or off-treatment (Apo A1 ITT population).
Arm/Group Title Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Number of Participants Analyzed 71 141
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-2.6  (1.6) 1.4  (1.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg/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 0.0382
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 4.0
Confidence Interval (2-Sided) 95%
0.2 to 7.9
Estimation Comments Alirocumab vs. Placebo
19.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 Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Number of Participants Analyzed 72 143
Mean (Standard Error)
Unit of Measure: percent change
-0.5  (2.4) -41.9  (1.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg/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, Robust
Comments Multiple imputation approach followed by a robust regression model.
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -41.4
Confidence Interval (2-Sided) 95%
-47.0 to -35.7
Estimation Comments Alirocumab vs. Placebo
20.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 Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Number of Participants Analyzed 72 143
Mean (Standard Error)
Unit of Measure: percent change
2.4  (3.7) -13.1  (2.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg/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 0.0007
Comments Threshold for significance ≤ 0.05.
Method Regression, Robust
Comments Multiple imputation approach followed by a robust regression model.
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -15.5
Confidence Interval (2-Sided) 95%
-24.4 to -6.6
Estimation Comments Alirocumab vs. Placebo
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 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 Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Number of Participants Analyzed 72 143
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-1.8  (1.2) 4.7  (0.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg/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 6.5
Confidence Interval (2-Sided) 95%
3.7 to 9.3
Estimation Comments Alirocumab vs. Placebo
22.Secondary Outcome
Title Percent Change From Baseline in Apo A1 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 A1 ITT population.
Arm/Group Title Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Number of Participants Analyzed 71 141
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-4.8  (1.1) 1.5  (0.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg/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 6.3
Confidence Interval (2-Sided) 95%
3.6 to 9.0
Estimation Comments Alirocumab vs. Placebo
23.Other Pre-specified 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 MMRM model including 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 Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Number of Participants Analyzed 72 143
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-3.6  (1.9) -62.5  (1.4)
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 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).
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Placebo Q2W Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Number of Participants Analyzed 71 143
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-3.4  (1.7) -64.6  (1.2)
Time Frame All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the ‘treatment-emergent period’ (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.
 
Arm/Group Title Placebo Q2W Alirocumab 75 mg/ Up to 150 mg Q2W
Hide Arm/Group Description Participants exposed to placebo (for alirocumab) SC injection Q2W added to stable LMT (mean exposition of 50 weeks). Participants exposed to alirocumab 75 mg /up to 150 mg SC injection Q2W added to stable LMT (mean exposition of 50 weeks).
All-Cause Mortality
Placebo Q2W Alirocumab 75 mg/ Up to 150 mg Q2W
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Q2W Alirocumab 75 mg/ Up to 150 mg Q2W
Affected / at Risk (%) Affected / at Risk (%)
Total   9/72 (12.50%)   10/143 (6.99%) 
Cardiac disorders     
Angina pectoris  1  0/72 (0.00%)  1/143 (0.70%) 
Congestive cardiomyopathy  1  0/72 (0.00%)  1/143 (0.70%) 
Myocardial infarction  1  1/72 (1.39%)  1/143 (0.70%) 
Coronary artery stenosis  1  1/72 (1.39%)  0/143 (0.00%) 
Ear and labyrinth disorders     
Sudden hearing loss  1  0/72 (0.00%)  1/143 (0.70%) 
Eye disorders     
Cataract  1  0/72 (0.00%)  1/143 (0.70%) 
Vitreous haemorrhage  1  0/72 (0.00%)  1/143 (0.70%) 
Gastrointestinal disorders     
Intestinal obstruction  1  1/72 (1.39%)  0/143 (0.00%) 
General disorders     
Medical device discomfort  1  1/72 (1.39%)  0/143 (0.00%) 
Infections and infestations     
Cellulitis  1  0/72 (0.00%)  1/143 (0.70%) 
Muscle abscess  1  0/72 (0.00%)  1/143 (0.70%) 
Pyelonephritis acute  1  1/72 (1.39%)  1/143 (0.70%) 
Injury, poisoning and procedural complications     
Road traffic accident  1  0/72 (0.00%)  1/143 (0.70%) 
Traumatic fracture  1  2/72 (2.78%)  1/143 (0.70%) 
Acetabulum fracture  1  0/72 (0.00%)  1/143 (0.70%) 
Clavicle fracture  1  0/72 (0.00%)  1/143 (0.70%) 
Rib fracture  1  0/72 (0.00%)  1/143 (0.70%) 
Scapula fracture  1  0/72 (0.00%)  1/143 (0.70%) 
Musculoskeletal and connective tissue disorders     
Spondylolisthesis  1  1/72 (1.39%)  0/143 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acoustic neuroma  1  0/72 (0.00%)  1/143 (0.70%) 
Pancreatic carcinoma  1  1/72 (1.39%)  0/143 (0.00%) 
Renal and urinary disorders     
Nephrotic syndrome  1  1/72 (1.39%)  0/143 (0.00%) 
Reproductive system and breast disorders     
Prostatitis  1  1/72 (1.39%)  0/143 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Q2W Alirocumab 75 mg/ Up to 150 mg Q2W
Affected / at Risk (%) Affected / at Risk (%)
Total   44/72 (61.11%)   97/143 (67.83%) 
Gastrointestinal disorders     
Dental caries  1  1/72 (1.39%)  9/143 (6.29%) 
Abdominal pain upper  1  4/72 (5.56%)  4/143 (2.80%) 
General disorders     
Injection site reaction  1  3/72 (4.17%)  18/143 (12.59%) 
Immune system disorders     
Seasonal allergy  1  5/72 (6.94%)  1/143 (0.70%) 
Infections and infestations     
Nasopharyngitis  1  26/72 (36.11%)  65/143 (45.45%) 
Pharyngitis  1  4/72 (5.56%)  9/143 (6.29%) 
Influenza  1  6/72 (8.33%)  1/143 (0.70%) 
Injury, poisoning and procedural complications     
Fall  1  5/72 (6.94%)  11/143 (7.69%) 
Contusion  1  3/72 (4.17%)  8/143 (5.59%) 
Metabolism and nutrition disorders     
Diabetes mellitus  1  4/72 (5.56%)  12/143 (8.39%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  4/72 (5.56%)  18/143 (12.59%) 
Arthralgia  1  6/72 (8.33%)  4/143 (2.80%) 
Musculoskeletal stiffness  1  4/72 (5.56%)  1/143 (0.70%) 
Vascular disorders     
Hypertension  1  5/72 (6.94%)  9/143 (6.29%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
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: NCT02107898     History of Changes
Other Study ID Numbers: EFC13672
U1111-1115-7486 ( Other Identifier: UTN )
First Submitted: April 4, 2014
First Posted: April 8, 2014
Results First Submitted: December 23, 2015
Results First Posted: January 29, 2016
Last Update Posted: October 4, 2016