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Phase III Study To Evaluate Alirocumab in Patients With Hypercholesterolemia Not Treated With a Statin (ODYSSEY CHOICE II)

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ClinicalTrials.gov Identifier: NCT02023879
Recruitment Status : Completed
First Posted : December 30, 2013
Results First Posted : March 15, 2017
Last Update Posted : July 27, 2018
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Hypercholesterolemia
Interventions Drug: Alirocumab
Drug: Placebo (for Alirocumab)
Drug: Non-statin LMT
Other: Diet Alone
Enrollment 233
Recruitment Details The study was conducted at 43 centers in 8 countries. A total of 402 participants were screened between December-2013 and May-2014, of whom 233 were randomized for double-blind (DB) treatment period and 169 were screen failures. Out of 233 randomized for DB period, 205 participants entered the optional open-label (OL) extension period.
Pre-assignment Details Randomization was stratified by statin intolerant status & background therapy (non-statin lipid therapy vs diet). Randomization followed a 1:2:1 ratio for placebo, Alirocumab 75 mg and Alirocumab 150 mg instead of 1:1:2 as initially planned due to systematic error in treatment allocation algorithm discovered after all participants were randomized.
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description

Period 1: Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.

Period 2: Alirocumab 150 mg SC injection every 4 weeks (Q4W) from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and low-density lipoprotein cholesterol (LDL-C) values. Subsequent down titration to 150 mg Q4W was allowed.

Period 1: Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.

Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed.

Period 1: Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.

Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed.

Period Title: Period 1: 24-Week Double-blind Treatment
Started 58 116 59
Treated 58 115 58
Completed 54 107 50
Not Completed 4 9 9
Reason Not Completed
Adverse Event             2             2             5
Poor compliance to protocol             0             2             1
Physician Decision             0             1             0
Consent withdrawn by participant             1             0             1
Randomized but not treated             0             1             1
Other than specified above             1             3             1
Period Title: Extension Open Label Treatment
Started 51 [1] 106 [1] 48 [1]
Completed 46 89 43
Not Completed 5 17 5
Reason Not Completed
Adverse Event             1             7             3
Poor compliance to protocol             1             1             0
Participant moved             1             2             0
Other than specified above             2             7             2
[1]
The open-label extension period was optional for participants who completed the double-blind period.
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) Alirocumab 150 mg Q4W/Up to 150 mg Q2W Total
Hide Arm/Group Description

Period 1: Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.

Period 2: Alirocumab 150 mg SC injection every 4 weeks (Q4W) from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and low-density lipoprotein cholesterol (LDL-C) values. Subsequent down titration to 150 mg Q4W was allowed.

Period 1: Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.

Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed.

Period 1: Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.

Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed.

Total of all reporting groups
Overall Number of Baseline Participants 58 116 59 233
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 58 participants 116 participants 59 participants 233 participants
63.1  (10.7) 62.5  (9.9) 64.2  (10.0) 63.1  (10.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants 116 participants 59 participants 233 participants
Female
27
  46.6%
47
  40.5%
29
  49.2%
103
  44.2%
Male
31
  53.4%
69
  59.5%
30
  50.8%
130
  55.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants 116 participants 59 participants 233 participants
Hispanic or Latino
1
   1.7%
7
   6.0%
4
   6.8%
12
   5.2%
Not Hispanic or Latino
57
  98.3%
109
  94.0%
54
  91.5%
220
  94.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
1
   1.7%
1
   0.4%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants 116 participants 59 participants 233 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   1.7%
4
   3.4%
3
   5.1%
8
   3.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   0.9%
0
   0.0%
1
   0.4%
Black or African American
1
   1.7%
3
   2.6%
1
   1.7%
5
   2.1%
White
56
  96.6%
108
  93.1%
55
  93.2%
219
  94.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Calculated LDL-C in mg/dL   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 58 participants 116 participants 59 participants 233 participants
158.5  (47.3) 154.5  (44.6) 163.9  (69.1) 157.9  (52.4)
[1]
Measure Description: Calculated LDL-C from Friedewald formula (LDL-C = Total cholesterol [Total-C] - High-Density Lipoprotein Cholesterol [HDL-C] - [Triglyceride/5]).
Calculated LDL-C in mmol/L  
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 58 participants 116 participants 59 participants 233 participants
4.106  (1.226) 4.002  (1.154) 4.245  (1.789) 4.089  (1.356)
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 that included 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 Q2W/Up to 150 mg Q2W (Calibrator) Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 57 115 58
Least Squares Mean (Standard Error)
Unit of Measure: percent change
4.7  (2.3) -53.5  (1.6) -51.7  (2.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Comments Alirocumab 150 mg Q4W/up to 150 mg Q2W 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 at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square (LS) mean difference
Estimated Value -56.4
Confidence Interval (2-Sided) 95%
-62.9 to -49.9
Estimation Comments Alirocumab 150 mg Q4W/Up to 150 mg Q2W 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 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 that included 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 Q2W/Up to 150 mg Q2W Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 56 115 57
Least Squares Mean (Standard Error)
Unit of Measure: percent change
5.1  (2.1) -55.3  (1.5) -54.6  (2.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 150 mg Q4W/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 at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -59.7
Confidence Interval (2-Sided) 95%
-65.6 to -53.8
Estimation Comments Alirocumab 150 mg Q4W/Up to 150 mg Q2W 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 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 Q2W/Up to 150 mg Q2W Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 57 115 58
Least Squares Mean (Standard Error)
Unit of Measure: percent change
3.2  (2.5) -50.8  (1.7) -41.7  (2.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 150 mg Q4W/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 at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -44.9
Confidence Interval (2-Sided) 95%
-51.8 to -38.1
Estimation Comments Alirocumab 150 mg Q4W/Up to 150 mg Q2W 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 Q2W/Up to 150 mg Q2W Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 56 115 57
Least Squares Mean (Standard Error)
Unit of Measure: percent change
3.6  (2.3) -51.5  (1.6) -44.8  (2.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 150 mg Q4W/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 at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -48.4
Confidence Interval (2-Sided) 95%
-54.8 to -41.9
Estimation Comments Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo
5.Secondary Outcome
Title Percent Change From Baseline in Calculated LDL-C to Averaged Weeks 9 to 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 and assigning a weight of 0.25 for Week 9, 10, 11 and 12 time points.
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 Q2W/Up to 150 mg Q2W Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 57 115 58
Least Squares Mean (Standard Error)
Unit of Measure: percent change
3.2  (2.0) -53.6  (1.4) -52.3  (2.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 150 mg Q4W/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 at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -55.5
Confidence Interval (2-Sided) 95%
-61.1 to -49.8
Estimation Comments Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo
6.Secondary Outcome
Title Percent Change From Baseline in Calculated LDL-C at Averaged Week 9 to 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) and assigning a weight of 0.25 for Week 9, 10, 11 and 12 time points.
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 Q2W/Up to 150 mg Q2W Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 56 115 57
Least Squares Mean (Standard Error)
Unit of Measure: percent change
3.6  (1.9) -54.1  (1.3) -55.0  (1.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 150 mg Q4W/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 at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -58.6
Confidence Interval (2-Sided) 95%
-63.8 to -53.4
Estimation Comments Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo
7.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 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. Number of participants analyzed = participants of the ITT population with available data at specified time-points.
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 56 112 58
Least Squares Mean (Standard Error)
Unit of Measure: percent change
7.5  (2.1) -39.7  (1.5) -38.9  (2.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 150 mg Q4W/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 at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -46.4
Confidence Interval (2-Sided) 95%
-52.4 to -40.4
Estimation Comments Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo
8.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 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. Number of participants analyzed = participants of the mITT population with available data at specified time-points.
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 54 112 54
Least Squares Mean (Standard Error)
Unit of Measure: percent change
7.7  (2.0) -41.2  (1.4) -40.9  (2.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 150 mg Q4W/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 at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -48.6
Confidence Interval (2-Sided) 95%
-54.3 to -42.8
Estimation Comments Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo
9.Secondary Outcome
Title Percent Change From Baseline in Non-HDL-C at Week 24 - ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 24 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 Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 57 115 58
Least Squares Mean (Standard Error)
Unit of Measure: percent change
4.8  (2.1) -45.3  (1.5) -44.2  (2.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 150 mg Q4W/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 at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -49.0
Confidence Interval (2-Sided) 95%
-54.9 to -43.2
Estimation Comments Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo
10.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
mITT population.
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 56 115 57
Least Squares Mean (Standard Error)
Unit of Measure: percent change
5.0  (1.9) -46.9  (1.3) -46.7  (1.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 150 mg Q4W/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 at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -51.7
Confidence Interval (2-Sided) 95%
-57.1 to -46.4
Estimation Comments Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo
11.Secondary Outcome
Title Percent Change From Baseline in Total-C at Week 24 - ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 24 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 Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 57 115 58
Least Squares Mean (Standard Error)
Unit of Measure: percent change
3.0  (1.6) -34.0  (1.1) -32.3  (1.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 150 mg Q4W/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 at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -35.3
Confidence Interval (2-Sided) 95%
-39.8 to -30.8
Estimation Comments Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo
12.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 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. Number of participants analyzed = participants of the ITT population with available data at specified time-points.
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 56 112 58
Least Squares Mean (Standard Error)
Unit of Measure: percent change
7.0  (2.2) -38.4  (1.6) -31.3  (2.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 150 mg Q4W/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 at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -38.2
Confidence Interval (2-Sided) 95%
-44.3 to -32.1
Estimation Comments Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo
13.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 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 Q2W/Up to 150 mg Q2W Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 57 115 58
Least Squares Mean (Standard Error)
Unit of Measure: percent change
3.0  (2.2) -43.4  (1.5) -34.9  (2.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 150 mg Q4W/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 at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -37.9
Confidence Interval (2-Sided) 95%
-43.9 to -31.8
Estimation Comments Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo
14.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 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 Q2W/Up to 150 mg Q2W Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 57 115 58
Least Squares Mean (Standard Error)
Unit of Measure: percent change
1.8  (1.6) -32.6  (1.2) -24.5  (1.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 150 mg Q4W/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 at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -26.3
Confidence Interval (2-Sided) 95%
-30.9 to -21.7
Estimation Comments Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo
15.Secondary Outcome
Title Percentage of Very High Cardiovascular (CV) Risk Participants Achieving Calculated LDL-C <70 mg/dL (<1.81 mmol/L) or Moderate or High CV Risk Participants Achieving Calculated LDL-C <100 mg/dL (<2.59 mmol/L) at Week 24 - ITT Analysis
Hide Description

Moderate CV risk: 10-year fatal cardiovascular disease (CVD) risk Systemic Coronary Risk Evaluation (SCORE) ≥1 and <5%.

High CV risk: 10-year fatal CVD risk SCORE ≥5% or moderate chronic kidney disease or type 1 or type 2 diabetes mellitus without target organ damage or familial hypercholesterolemia.

Very high CV risk: history of documented coronary heart disease, ischemic stroke, peripheral artery disease, transient ischemic attack, abdominal aortic aneurysm, or carotid artery occlusion >50% without symptoms; carotid endarterectomy or carotid artery stent procedure; renal artery stenosis, or renal artery stent procedure; or type 1 or type 2 diabetes mellitus with target organ damage.

Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included.

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 Q2W/Up to 150 mg Q2W Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 57 115 58
Measure Type: Number
Unit of Measure: percentage of participants
1.8 70.3 63.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 150 mg Q4W/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 at 0.05 level.
Method Regression, Logistic
Comments Multiple imputation approach followed by logistic regression model.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 279.8
Confidence Interval (2-Sided) 95%
29.1 to 2690.1
Estimation Comments Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo
16.Secondary Outcome
Title Percentage of Very High CV Risk Participants Achieving Calculated LDL-C< 70 mg/dL (<1.81 mmol/L) or Moderate or High CV Risk Participants Achieving Calculated LDL-C< 100 mg/dL (<2.59 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 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 Q2W/Up to 150 mg Q2W Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 56 115 57
Measure Type: Number
Unit of Measure: percentage of participants
1.8 72.7 67.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 150 mg Q4W/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 at 0.05 level.
Method Regression, Logistic
Comments Multiple imputation approach followed by logistic regression model.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 354.7
Confidence Interval (2-Sided) 95%
36.2 to 3479.5
Estimation Comments Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo
17.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 last observation carried forward (LOCF) approach 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 Q2W/Up to 150 mg Q2W Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 57 115 58
Measure Type: Number
Unit of Measure: percentage of participants
0.0 60.0 50.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 150 mg Q4W/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 at 0.05 level.
Method Regression, Logistic
Comments LOCF approach followed by logistic regression model.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 126.0
Confidence Interval (2-Sided) 95%
20.0 to 9999
Estimation Comments Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo (Confidence interval should be read as 20.0 to >9999)
18.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 LOCF approach 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 Q2W/Up to 150 mg Q2W Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 56 115 57
Measure Type: Number
Unit of Measure: percentage of participants
0.0 61.7 50.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 150 mg Q4W/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 at 0.05 level.
Method Regression, Logistic
Comments LOCF approach followed by logistic regression model.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 141.5
Confidence Interval (2-Sided) 95%
22.2 to 9999
Estimation Comments Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo (Confidence interval should be read as 20.0 to >9999)
19.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 Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 57 115 58
Mean (Standard Error)
Unit of Measure: percent change
4.1  (3.7) -21.8  (2.6) -15.5  (3.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 150 mg Q4W/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 0.0002
Comments Threshold for significance at 0.05 level.
Method Regression, Robust
Comments Multiple imputation approach followed by robust regression model.
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -19.6
Confidence Interval (2-Sided) 95%
-29.8 to -9.4
Estimation Comments Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo
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 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 Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 57 115 58
Mean (Standard Error)
Unit of Measure: percent change
2.2  (3.4) -16.5  (2.4) -5.7  (3.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 150 mg Q4W/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 0.0892
Comments Threshold for significance at 0.05 level.
Method Regression, Robust
Comments Multiple imputation approach followed by robust regression model.
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -7.9
Confidence Interval (2-Sided) 95%
-17.1 to 1.2
Estimation Comments Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo
21.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 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 Q2W/Up to 150 mg Q2W Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 57 115 58
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-2.4  (1.9) 7.4  (1.4) 7.7  (2.0)
22.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 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 Q2W/Up to 150 mg Q2W Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 57 115 58
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-0.8  (1.9) 6.8  (1.3) 8.6  (1.9)
23.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 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 Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 57 115 58
Mean (Standard Error)
Unit of Measure: percent change
1.1  (3.8) -10.6  (2.7) -9.2  (3.9)
24.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 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 Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 57 115 58
Mean (Standard Error)
Unit of Measure: percent change
2.1  (3.9) -11.3  (2.7) -3.0  (3.8)
25.Secondary Outcome
Title Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 24 from MMRM 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. Number of participants analyzed = participants of the ITT population with available data at specified time-points.
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 56 112 58
Least Squares Mean (Standard Error)
Unit of Measure: percent change
3.4  (1.5) 8.2  (1.1) 10.0  (1.5)
26.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 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. Number of participants analyzed = participants of the ITT population with available data at specified time-points.
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed 56 112 58
Least Squares Mean (Standard Error)
Unit of Measure: percent change
2.6  (1.5) 5.9  (1.1) 7.6  (1.5)
27.Other Pre-specified Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase
Hide Description Mean percent changes (and standard deviations) observed during the open-label extension period are provided.
Time Frame Baseline, Week 32, 36, 48, 72, 96, 120, 144 and Week 168
Hide Outcome Measure Data
Hide Analysis Population Description
Open-label extension population included all participants who received at least one dose or part of dose of Alirocumab during the open label extension period. Here, “number analyzed” signifies the number of participants evaluable for each specified time-point.
Arm/Group Title Alirocumab 150 mg Q4W (After Placebo Q2W) Alirocumab 150 mg QW4 (After Alirocumab 75 Q2W/Up 150 Q2W) Alirocumab 150 mg Q4W (After Alirocumab 150 Q4W/Up 150 Q2W)
Hide Arm/Group Description:
Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first, in participants who received placebo (for Alirocumab) Q2W for 24 weeks during the double-blind period. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and low-density lipoprotein cholesterol (LDL-C) values. Subsequent down titration to 150 mg Q4W was allowed.
Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first, in participants who received Alirocumab 75 mg Q2W/Up to 150 mg Q2W for 24 weeks during the double-blind period. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and low-density lipoprotein cholesterol (LDL-C) values. Subsequent down titration to 150 mg Q4W was allowed.
Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first, in participants who received 150 mg Q4W/Up to 150 mg Q2W for 24 weeks during the double-blind period. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and low-density lipoprotein cholesterol (LDL-C) values. Subsequent down titration to 150 mg Q4W was allowed.
Overall Number of Participants Analyzed 51 106 48
Mean (Standard Deviation)
Unit of Measure: percent change
Week 32 Number Analyzed 48 participants 98 participants 45 participants
-37.3  (18.8) -41.1  (21.2) -46.9  (13.3)
Week 36 Number Analyzed 48 participants 96 participants 46 participants
-36.1  (22.0) -39.2  (21.2) -43.1  (13.7)
Week 48 Number Analyzed 47 participants 91 participants 44 participants
-46.5  (24.2) -49.2  (18.7) -48.7  (21.7)
Week 72 Number Analyzed 50 participants 94 participants 47 participants
-50.8  (20.6) -53.7  (19.5) -52.3  (21.3)
Week 96 Number Analyzed 48 participants 90 participants 44 participants
-49.8  (20.4) -52.8  (19.6) -46.8  (22.0)
Week 120 Number Analyzed 46 participants 81 participants 37 participants
-50.6  (20.9) -53.7  (18.7) -51.8  (24.1)
Week 144 Number Analyzed 38 participants 72 participants 29 participants
-52.7  (17.6) -48.7  (23.7) -49.4  (20.9)
Week 168 Number Analyzed 4 participants 13 participants 4 participants
-47.8  (24.2) -66.2  (17.1) -60.0  (4.6)
Time Frame All Adverse Events (AE) were collected from signature of informed consent form up to study completion (up to 176 weeks) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description Reported AEs/deaths are treatment-emergent ie; AEs that developed/worsened and deaths that occurred ‘on treatment’; from 1st dose up to last dose (active/placebo depending on Q2W/Q4W dosing) in DB period+70 days, truncated at the day before 1st dose in OL period for participants entering in OL period; from 1st dose up to last dose in OL period+70 days.
 
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up150 mg Q2W Alirocumab 150 mg Q4W/Up150 mg Q2W Alirocumab 150 mg Q4W (After Placebo Q2W) Alirocumab 150 mg Q4W (After Alirocumab 75 Q2W/Up150 Q2W) Alirocumab 150 mg Q4W (After Alirocumab 150 Q4W/Up150 Q2W)
Hide Arm/Group Description Participants exposed to placebo SC injection Q2W added to stable non-statin LMT or diet alone (mean exposure of 23 weeks). Participants exposed to alirocumab 75 mg Q2W/up to 150 mg Q2W SC injection added to stable non-statin LMT or diet alone (mean exposure of 23 weeks). Participants exposed to alirocumab 150 mg Q4W/up to 150 mg Q2W SC injection added to stable non-statin LMT or diet alone (mean exposure of 22 weeks). Participants exposed to alirocumab 150 mg Q4W SC injection added to stable non-statin LMT or diet alone (mean exposure of 128 weeks) after having received Placebo Q2W for 24 weeks. Participants exposed to alirocumab 150 mg Q4W SC injection added to stable non-statin LMT or diet alone (mean exposure of 117 weeks) after having received Alirocumab 75 mg Q2W/Up to 150 mg Q2W for 24 weeks. Participants exposed to alirocumab 150 mg Q4W SC injection added to stable non-statin LMT or diet alone (mean exposure of 119 weeks) after having received Alirocumab 150 mg Q4W/Up to 150 mg Q2W for 24 weeks.
All-Cause Mortality
Placebo Q2W Alirocumab 75 mg Q2W/Up150 mg Q2W Alirocumab 150 mg Q4W/Up150 mg Q2W Alirocumab 150 mg Q4W (After Placebo Q2W) Alirocumab 150 mg Q4W (After Alirocumab 75 Q2W/Up150 Q2W) Alirocumab 150 mg Q4W (After Alirocumab 150 Q4W/Up150 Q2W)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/58 (0.00%)   0/115 (0.00%)   0/58 (0.00%)   0/51 (0.00%)   2/106 (1.89%)   1/48 (2.08%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Q2W Alirocumab 75 mg Q2W/Up150 mg Q2W Alirocumab 150 mg Q4W/Up150 mg Q2W Alirocumab 150 mg Q4W (After Placebo Q2W) Alirocumab 150 mg Q4W (After Alirocumab 75 Q2W/Up150 Q2W) Alirocumab 150 mg Q4W (After Alirocumab 150 Q4W/Up150 Q2W)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/58 (6.90%)   7/115 (6.09%)   7/58 (12.07%)   15/51 (29.41%)   28/106 (26.42%)   14/48 (29.17%) 
Blood and lymphatic system disorders             
Anaemia  1  1/58 (1.72%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  0/106 (0.00%)  0/48 (0.00%) 
Haemorrhagic anaemia  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  1/51 (1.96%)  1/106 (0.94%)  0/48 (0.00%) 
Cardiac disorders             
Acute coronary syndrome  1  0/58 (0.00%)  1/115 (0.87%)  0/58 (0.00%)  0/51 (0.00%)  0/106 (0.00%)  0/48 (0.00%) 
Acute myocardial infarction  1  0/58 (0.00%)  0/115 (0.00%)  1/58 (1.72%)  0/51 (0.00%)  3/106 (2.83%)  0/48 (0.00%) 
Angina pectoris  1  0/58 (0.00%)  1/115 (0.87%)  0/58 (0.00%)  1/51 (1.96%)  0/106 (0.00%)  0/48 (0.00%) 
Angina unstable  1  0/58 (0.00%)  0/115 (0.00%)  1/58 (1.72%)  0/51 (0.00%)  0/106 (0.00%)  0/48 (0.00%) 
Aortic valve stenosis  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Atrial fibrillation  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  1/51 (1.96%)  0/106 (0.00%)  1/48 (2.08%) 
Cardiac failure congestive  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  1/51 (1.96%)  2/106 (1.89%)  0/48 (0.00%) 
Cardio-respiratory arrest  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  0/106 (0.00%)  1/48 (2.08%) 
Cardiomyopathy  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  1/51 (1.96%)  0/106 (0.00%)  0/48 (0.00%) 
Coronary artery disease  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  2/106 (1.89%)  1/48 (2.08%) 
Mitral valve incompetence  1  1/58 (1.72%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  0/106 (0.00%)  0/48 (0.00%) 
Myocardial infarction  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Ear and labyrinth disorders             
Vertigo  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Endocrine disorders             
Basedow's disease  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Eye disorders             
Retinal detachment  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Gastrointestinal disorders             
Abdominal pain  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Abdominal pain upper  1  0/58 (0.00%)  1/115 (0.87%)  0/58 (0.00%)  0/51 (0.00%)  0/106 (0.00%)  0/48 (0.00%) 
Abdominal wall haematoma  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Constipation  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  1/51 (1.96%)  0/106 (0.00%)  0/48 (0.00%) 
Faecaloma  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  0/106 (0.00%)  1/48 (2.08%) 
Gastrointestinal haemorrhage  1  1/58 (1.72%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Retroperitoneal haematoma  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Small intestinal obstruction  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  1/48 (2.08%) 
Volvulus  1  0/58 (0.00%)  0/115 (0.00%)  1/58 (1.72%)  0/51 (0.00%)  0/106 (0.00%)  0/48 (0.00%) 
General disorders             
Chest pain  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Non-cardiac chest pain  1  0/58 (0.00%)  1/115 (0.87%)  0/58 (0.00%)  0/51 (0.00%)  2/106 (1.89%)  0/48 (0.00%) 
Hepatobiliary disorders             
Biliary colic  1  0/58 (0.00%)  1/115 (0.87%)  0/58 (0.00%)  0/51 (0.00%)  0/106 (0.00%)  0/48 (0.00%) 
Cholelithiasis  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Infections and infestations             
Appendicitis  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  1/51 (1.96%)  0/106 (0.00%)  0/48 (0.00%) 
Arthritis bacterial  1  0/58 (0.00%)  1/115 (0.87%)  0/58 (0.00%)  0/51 (0.00%)  0/106 (0.00%)  0/48 (0.00%) 
Cellulitis  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  0/106 (0.00%)  1/48 (2.08%) 
Device related infection  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Hepatitis E  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  1/51 (1.96%)  0/106 (0.00%)  0/48 (0.00%) 
Pneumonia  1  0/58 (0.00%)  1/115 (0.87%)  0/58 (0.00%)  1/51 (1.96%)  1/106 (0.94%)  2/48 (4.17%) 
Urinary tract infection  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  1/51 (1.96%)  0/106 (0.00%)  0/48 (0.00%) 
Injury, poisoning and procedural complications             
Craniocerebral injury  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  1/51 (1.96%)  0/106 (0.00%)  0/48 (0.00%) 
Fall  1  1/58 (1.72%)  0/115 (0.00%)  0/58 (0.00%)  2/51 (3.92%)  1/106 (0.94%)  0/48 (0.00%) 
Femur fracture  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Humerus fracture  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  1/51 (1.96%)  0/106 (0.00%)  0/48 (0.00%) 
Intentional overdose  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Jaw fracture  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  0/106 (0.00%)  1/48 (2.08%) 
Multiple fractures  1  1/58 (1.72%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  0/106 (0.00%)  0/48 (0.00%) 
Post procedural haematoma  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Radius fracture  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  1/51 (1.96%)  0/106 (0.00%)  0/48 (0.00%) 
Rib fracture  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  1/51 (1.96%)  0/106 (0.00%)  0/48 (0.00%) 
Road traffic accident  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  1/51 (1.96%)  0/106 (0.00%)  0/48 (0.00%) 
Spinal fracture  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  1/51 (1.96%)  0/106 (0.00%)  0/48 (0.00%) 
Subdural haematoma  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  1/51 (1.96%)  1/106 (0.94%)  0/48 (0.00%) 
Traumatic haemothorax  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  1/51 (1.96%)  0/106 (0.00%)  0/48 (0.00%) 
Traumatic renal injury  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  1/51 (1.96%)  0/106 (0.00%)  0/48 (0.00%) 
Vascular pseudoaneurysm  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Musculoskeletal and connective tissue disorders             
Arthritis  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  0/106 (0.00%)  1/48 (2.08%) 
Lumbar spinal stenosis  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  0/106 (0.00%)  1/48 (2.08%) 
Musculoskeletal chest pain  1  1/58 (1.72%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  0/106 (0.00%)  1/48 (2.08%) 
Myalgia  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  0/106 (0.00%)  1/48 (2.08%) 
Osteoarthritis  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  1/48 (2.08%) 
Rhabdomyolysis  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  0/106 (0.00%)  1/48 (2.08%) 
Rheumatoid arthritis  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  1/51 (1.96%)  0/106 (0.00%)  0/48 (0.00%) 
Spinal osteoarthritis  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Adenocarcinoma of colon  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  1/51 (1.96%)  0/106 (0.00%)  0/48 (0.00%) 
Basal cell carcinoma  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  1/51 (1.96%)  2/106 (1.89%)  1/48 (2.08%) 
Benign fallopian tube neoplasm  1  0/58 (0.00%)  1/115 (0.87%)  0/58 (0.00%)  0/51 (0.00%)  0/106 (0.00%)  0/48 (0.00%) 
Bladder transitional cell carcinoma  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Breast cancer  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  0/106 (0.00%)  1/48 (2.08%) 
Meningioma  1  0/58 (0.00%)  0/115 (0.00%)  1/58 (1.72%)  0/51 (0.00%)  0/106 (0.00%)  0/48 (0.00%) 
Oesophageal squamous cell carcinoma  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  1/51 (1.96%)  0/106 (0.00%)  0/48 (0.00%) 
Prostate cancer  1  1/58 (1.72%)  1/115 (0.87%)  0/58 (0.00%)  1/51 (1.96%)  2/106 (1.89%)  0/48 (0.00%) 
Skin cancer  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Uterine leiomyoma  1  0/58 (0.00%)  1/115 (0.87%)  0/58 (0.00%)  0/51 (0.00%)  0/106 (0.00%)  0/48 (0.00%) 
Nervous system disorders             
Arachnoiditis  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Cerebellar infarction  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  0/106 (0.00%)  1/48 (2.08%) 
Cerebrovascular accident  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Essential tremor  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  1/51 (1.96%)  0/106 (0.00%)  0/48 (0.00%) 
Hypoxic-ischaemic encephalopathy  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  0/106 (0.00%)  1/48 (2.08%) 
Multiple sclerosis relapse  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Presyncope  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  2/106 (1.89%)  0/48 (0.00%) 
Syncope  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  3/106 (2.83%)  2/48 (4.17%) 
Transient ischaemic attack  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Psychiatric disorders             
Depression  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Mental disorder  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  0/106 (0.00%)  1/48 (2.08%) 
Suicide attempt  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Renal and urinary disorders             
Acute kidney injury  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  1/51 (1.96%)  0/106 (0.00%)  0/48 (0.00%) 
Nephrolithiasis  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  1/51 (1.96%)  0/106 (0.00%)  0/48 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Chronic obstructive pulmonary disease  1  0/58 (0.00%)  0/115 (0.00%)  1/58 (1.72%)  0/51 (0.00%)  0/106 (0.00%)  1/48 (2.08%) 
Epistaxis  1  0/58 (0.00%)  1/115 (0.87%)  0/58 (0.00%)  0/51 (0.00%)  0/106 (0.00%)  0/48 (0.00%) 
Pulmonary embolism  1  0/58 (0.00%)  0/115 (0.00%)  1/58 (1.72%)  0/51 (0.00%)  0/106 (0.00%)  0/48 (0.00%) 
Vascular disorders             
Haematoma  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Hypertensive crisis  1  0/58 (0.00%)  1/115 (0.87%)  0/58 (0.00%)  0/51 (0.00%)  0/106 (0.00%)  0/48 (0.00%) 
Hypotension  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  2/106 (1.89%)  0/48 (0.00%) 
Hypovolaemic shock  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
Peripheral artery occlusion  1  0/58 (0.00%)  0/115 (0.00%)  1/58 (1.72%)  0/51 (0.00%)  0/106 (0.00%)  0/48 (0.00%) 
Peripheral artery stenosis  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  0/106 (0.00%)  1/48 (2.08%) 
Peripheral ischaemia  1  0/58 (0.00%)  0/115 (0.00%)  0/58 (0.00%)  0/51 (0.00%)  1/106 (0.94%)  0/48 (0.00%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
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 Q2W/Up150 mg Q2W Alirocumab 150 mg Q4W/Up150 mg Q2W Alirocumab 150 mg Q4W (After Placebo Q2W) Alirocumab 150 mg Q4W (After Alirocumab 75 Q2W/Up150 Q2W) Alirocumab 150 mg Q4W (After Alirocumab 150 Q4W/Up150 Q2W)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   28/58 (48.28%)   61/115 (53.04%)   29/58 (50.00%)   42/51 (82.35%)   71/106 (66.98%)   31/48 (64.58%) 
Gastrointestinal disorders             
Diarrhoea  1  2/58 (3.45%)  5/115 (4.35%)  1/58 (1.72%)  3/51 (5.88%)  11/106 (10.38%)  2/48 (4.17%) 
Nausea  1  2/58 (3.45%)  6/115 (5.22%)  3/58 (5.17%)  1/51 (1.96%)  3/106 (2.83%)  3/48 (6.25%) 
General disorders             
Fatigue  1  0/58 (0.00%)  5/115 (4.35%)  4/58 (6.90%)  3/51 (5.88%)  7/106 (6.60%)  3/48 (6.25%) 
Injection site reaction  1  0/58 (0.00%)  4/115 (3.48%)  8/58 (13.79%)  1/51 (1.96%)  7/106 (6.60%)  7/48 (14.58%) 
Non-cardiac chest pain  1  3/58 (5.17%)  3/115 (2.61%)  0/58 (0.00%)  6/51 (11.76%)  5/106 (4.72%)  1/48 (2.08%) 
Oedema peripheral  1  4/58 (6.90%)  3/115 (2.61%)  0/58 (0.00%)  4/51 (7.84%)  5/106 (4.72%)  5/48 (10.42%) 
Infections and infestations             
Bronchitis  1  0/58 (0.00%)  1/115 (0.87%)  1/58 (1.72%)  3/51 (5.88%)  4/106 (3.77%)  5/48 (10.42%) 
Influenza  1  0/58 (0.00%)  3/115 (2.61%)  1/58 (1.72%)  3/51 (5.88%)  9/106 (8.49%)  4/48 (8.33%) 
Pharyngitis  1  0/58 (0.00%)  1/115 (0.87%)  0/58 (0.00%)  3/51 (5.88%)  1/106 (0.94%)  0/48 (0.00%) 
Sinusitis  1  1/58 (1.72%)  1/115 (0.87%)  0/58 (0.00%)  3/51 (5.88%)  3/106 (2.83%)  1/48 (2.08%) 
Upper respiratory tract infection  1  4/58 (6.90%)  4/115 (3.48%)  3/58 (5.17%)  7/51 (13.73%)  8/106 (7.55%)  4/48 (8.33%) 
Urinary tract infection  1  1/58 (1.72%)  4/115 (3.48%)  4/58 (6.90%)  4/51 (7.84%)  7/106 (6.60%)  5/48 (10.42%) 
Viral upper respiratory tract infection  1  3/58 (5.17%)  10/115 (8.70%)  5/58 (8.62%)  5/51 (9.80%)  16/106 (15.09%)  9/48 (18.75%) 
Injury, poisoning and procedural complications             
Fall  1  1/58 (1.72%)  6/115 (5.22%)  0/58 (0.00%)  6/51 (11.76%)  14/106 (13.21%)  2/48 (4.17%) 
Laceration  1  0/58 (0.00%)  0/115 (0.00%)  1/58 (1.72%)  3/51 (5.88%)  3/106 (2.83%)  0/48 (0.00%) 
Metabolism and nutrition disorders             
Gout  1  0/58 (0.00%)  0/115 (0.00%)  1/58 (1.72%)  5/51 (9.80%)  5/106 (4.72%)  1/48 (2.08%) 
Hyperkalaemia  1  1/58 (1.72%)  0/115 (0.00%)  0/58 (0.00%)  1/51 (1.96%)  1/106 (0.94%)  3/48 (6.25%) 
Musculoskeletal and connective tissue disorders             
Arthralgia  1  4/58 (6.90%)  8/115 (6.96%)  7/58 (12.07%)  8/51 (15.69%)  7/106 (6.60%)  3/48 (6.25%) 
Back pain  1  0/58 (0.00%)  5/115 (4.35%)  2/58 (3.45%)  4/51 (7.84%)  10/106 (9.43%)  7/48 (14.58%) 
Muscle spasms  1  0/58 (0.00%)  9/115 (7.83%)  3/58 (5.17%)  4/51 (7.84%)  4/106 (3.77%)  1/48 (2.08%) 
Musculoskeletal pain  1  1/58 (1.72%)  3/115 (2.61%)  0/58 (0.00%)  1/51 (1.96%)  6/106 (5.66%)  2/48 (4.17%) 
Myalgia  1  3/58 (5.17%)  7/115 (6.09%)  3/58 (5.17%)  7/51 (13.73%)  6/106 (5.66%)  1/48 (2.08%) 
Neck pain  1  0/58 (0.00%)  2/115 (1.74%)  0/58 (0.00%)  3/51 (5.88%)  0/106 (0.00%)  0/48 (0.00%) 
Osteoarthritis  1  2/58 (3.45%)  0/115 (0.00%)  0/58 (0.00%)  8/51 (15.69%)  7/106 (6.60%)  3/48 (6.25%) 
Pain in extremity  1  2/58 (3.45%)  4/115 (3.48%)  3/58 (5.17%)  2/51 (3.92%)  3/106 (2.83%)  1/48 (2.08%) 
Nervous system disorders             
Dizziness  1  4/58 (6.90%)  1/115 (0.87%)  4/58 (6.90%)  4/51 (7.84%)  5/106 (4.72%)  4/48 (8.33%) 
Headache  1  4/58 (6.90%)  10/115 (8.70%)  5/58 (8.62%)  3/51 (5.88%)  6/106 (5.66%)  4/48 (8.33%) 
Psychiatric disorders             
Depression  1  0/58 (0.00%)  2/115 (1.74%)  1/58 (1.72%)  1/51 (1.96%)  7/106 (6.60%)  0/48 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Cough  1  0/58 (0.00%)  3/115 (2.61%)  1/58 (1.72%)  9/51 (17.65%)  9/106 (8.49%)  1/48 (2.08%) 
Skin and subcutaneous tissue disorders             
Dry skin  1  1/58 (1.72%)  0/115 (0.00%)  1/58 (1.72%)  3/51 (5.88%)  0/106 (0.00%)  0/48 (0.00%) 
Rash  1  0/58 (0.00%)  1/115 (0.87%)  3/58 (5.17%)  0/51 (0.00%)  3/106 (2.83%)  1/48 (2.08%) 
Vascular disorders             
Hypertension  1  2/58 (3.45%)  1/115 (0.87%)  2/58 (3.45%)  2/51 (3.92%)  8/106 (7.55%)  2/48 (4.17%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
The systematic randomization error was not anticipated to have an impact on the power of the study. The sample size to detect a difference in efficacy endpoints was reached (it was increased to obtain additional safety data) and blind was maintained.
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: NCT02023879     History of Changes
Other Study ID Numbers: EFC13786
2013-002659-14 ( EudraCT Number )
U1111-1146-3517 ( Other Identifier: UTN )
First Submitted: December 6, 2013
First Posted: December 30, 2013
Results First Submitted: January 24, 2017
Results First Posted: March 15, 2017
Last Update Posted: July 27, 2018