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Trial record 1 of 1 for:    NCT01730053
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Study of Alirocumab (REGN727/SAR236553) added-on to Rosuvastatin Versus Other Lipid Modifying Treatments (LMT) (ODYSSEY OPTIONS II)

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ClinicalTrials.gov Identifier: NCT01730053
Recruitment Status : Completed
First Posted : November 21, 2012
Results First Posted : October 28, 2015
Last Update Posted : April 7, 2020
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Hypercholesterolemia
Interventions Drug: Alirocumab
Drug: Rosuvastatin
Drug: Ezetimibe
Drug: Placebo
Enrollment 305
Recruitment Details The study was conducted at 79 sites in 8 countries. Overall, 672 participants were screened between 24 October 2012 and 27 September 2013, 367 of whom were screen failures. Screen failures were mainly due to exclusion criteria met.
Pre-assignment Details Randomization was stratified according to prior history of myocardial infarction or ischemic stroke, and intensity of statin treatment (rosuvastatin 10 or 20 mg). Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System (IVWRS) in a 1:1:1:1:1:1 ratio after confirmation of selection criteria.
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks. Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks. Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history. Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks. Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Period Title: Overall Study
Started 48 48 49 53 53 54
Treated 48 48 49 53 53 54
Completed 43 34 38 45 44 41
Not Completed 5 14 11 8 9 13
Reason Not Completed
Participant moved             0             0             1             0             0             0
Physician Decision             0             0             0             1             0             0
Adverse Event             2             6             3             3             2             2
Poor compliance to protocol             1             2             2             0             0             2
Other than specified             2             6             5             4             7             9
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75/up to 150 + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg Total
Hide Arm/Group Description Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks. Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks. Participants, who were receiving rosuvastatin 10 mg over-encapsulated tablet orally at baseline, received alirocumab 75 mg SC injection Q2W, rosuvastatin 10 mg over-encapsulated tablet orally QD, and placebo for ezetimibe over-encapsulated tablet orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history. Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks. Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history. Total of all reporting groups
Overall Number of Baseline Participants 48 48 49 53 53 54 305
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 48 participants 48 participants 49 participants 53 participants 53 participants 54 participants 305 participants
61.5  (11.15) 60.4  (10.38) 62.2  (11.11) 60.6  (10.11) 63.1  (10.2) 57.9  (8.86) 60.9  (10.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 48 participants 48 participants 49 participants 53 participants 53 participants 54 participants 305 participants
Female
15
  31.3%
22
  45.8%
18
  36.7%
15
  28.3%
22
  41.5%
26
  48.1%
118
  38.7%
Male
33
  68.8%
26
  54.2%
31
  63.3%
38
  71.7%
31
  58.5%
28
  51.9%
187
  61.3%
Low density lipoprotein cholesterol (LDL-C) in mg/dL   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 48 participants 48 participants 49 participants 53 participants 53 participants 54 participants 305 participants
105.9  (36.0) 102.4  (41.9) 107.3  (26.4) 112.9  (43.3) 119.0  (48.0) 118.3  (32.2) 111.3  (39.0)
[1]
Measure Description: Calculated LDL-C from Friedewald formula.
LDL-C in mmol/L   [1] 
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 48 participants 48 participants 49 participants 53 participants 53 participants 54 participants 305 participants
2.743  (0.933) 2.653  (1.085) 2.78  (0.684) 2.924  (1.122) 3.082  (1.243) 3.065  (0.834) 2.882  (1.009)
[1]
Measure Description: Calculated LDL-C from Friedewald formula.
1.Primary Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis
Hide Description Calculated LDL-C values were obtained from Friedewald formula. Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population: all randomized participants with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment.
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description:
Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Overall Number of Participants Analyzed 48 47 48 52 50 53
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-16.3  (4.1) -14.4  (4.4) -50.6  (4.2) -15.9  (7.1) -11.0  (7.2) -36.3  (7.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rosuvastatin 20 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Alirocumab group was compared to the corresponding active control group using an appropriate contrast statement.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -34.2
Confidence Interval (2-Sided) 98.75%
-49.2 to -19.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg + Rosuvastatin 10 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments As described in statistical analysis 1 of the endpoint.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -36.1
Confidence Interval (2-Sided) 98.75%
-51.5 to -20.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rosuvastatin 40 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Comments As described in statistical analysis 1 of the endpoint.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0453
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -20.3
Confidence Interval (2-Sided) 98.75%
-45.8 to 5.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg + Rosuvastatin 20 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Comments As described in statistical analysis 1 of the endpoint.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0136
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -25.3
Confidence Interval (2-Sided) 98.75%
-50.9 to 0.3
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis
Hide Description Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (ie. up to 21 days after last injection or 3 days after the last capsule [whatever rosuvastatin or ezetimibe], whichever came first) (on-treatment analysis).
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT (mITT) population: all randomized and treated participants with one baseline and at least one post-baseline calculated LDL-C value on-treatment.
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description:
Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Overall Number of Participants Analyzed 48 46 48 50 50 51
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-18.3  (3.3) -20.3  (3.6) -53.5  (3.5) -17.0  (6.9) -16.5  (6.9) -41.5  (6.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rosuvastatin 20 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 1.25 % level.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -35.2
Confidence Interval (2-Sided) 98.75%
-47.4 to -23.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg + Rosuvastatin 10 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Analysis description as per the statistical analysis 1 of this endpoint.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -33.2
Confidence Interval (2-Sided) 98.75%
-45.9 to -20.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rosuvastatin 40 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Comments Analysis description as per the statistical analysis 1 of this endpoint.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0131
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -24.5
Confidence Interval (2-Sided) 98.75%
-49.2 to 0.2
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
Hide Description Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment (ITT analysis).
Time Frame From Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description:
Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Overall Number of Participants Analyzed 48 47 48 52 50 53
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-17.1  (4.1) -17.4  (4.2) -49.6  (4.1) -22.1  (5.3) -19.3  (5.4) -32.3  (5.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rosuvastatin 20 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification).
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -35.2
Confidence Interval (2-Sided) 98.75%
-47.4 to -17.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg + Rosuvastatin 10 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Analysis description as per the statistical analysis 1 of this endpoint.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -32.2
Confidence Interval (2-Sided) 98.75%
-47 to -17.5
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
Hide Description Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule [whatever rosuvastatin or ezetimibe], whichever came first) (on-treatment analysis).
Time Frame From Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description:
Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Overall Number of Participants Analyzed 48 46 48 50 50 51
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-17.2  (3.6) -20.3  (3.8) -52.6  (3.6) -22.9  (5.2) -21.8  (5.2) -35.1  (5.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rosuvastatin 20 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification).
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -35.3
Confidence Interval (2-Sided) 98.75%
-48.2 to -22.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg + Rosuvastatin 10 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Analysis description as per the statistical analysis 1 of this endpoint.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -32.3
Confidence Interval (2-Sided) 98.75%
-45.6 to -19.0
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline Apo B value on- or off-treatment.
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description:
Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Overall Number of Participants Analyzed 44 44 44 51 48 49
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-7.3  (3.0) -9.7  (3.1) -36.5  (3.1) -9.8  (4.1) -11.2  (4.3) -28.3  (4.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rosuvastatin 20 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification).
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -29.2
Confidence Interval (2-Sided) 98.75%
-40.1 to -18.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg + Rosuvastatin 10 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Analysis description as per the statistical analysis 1 of this endpoint.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -26.8
Confidence Interval (2-Sided) 98.75%
-37.9 to -15.7
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis
Hide Description Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (ie. up to 21 days after last injection or 3 days after the last capsule [whatever rosuvastatin or ezetimibe], whichever came first).
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed: participants of the mITT population with one baseline and at least one post-baseline Apo B value on-treatment.
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description:
Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Overall Number of Participants Analyzed 44 42 43 50 47 48
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-8.8  (2.6) -11.2  (2.7) -39.5  (2.6) -12.7  (4.0) -12.6  (4.1) -30.4  (4.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rosuvastatin 20 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification).
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -30.7
Confidence Interval (2-Sided) 98.75%
-40.1 to -21.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg + Rosuvastatin 10 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Analysis description as per the statistical analysis 1 of this endpoint.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -28.3
Confidence Interval (2-Sided) 98.75%
-38.0 to -18.7
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline non-HDL-C value on- or off-treatment.
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description:
Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Overall Number of Participants Analyzed 48 47 48 52 50 53
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-11.3  (3.4) -13.4  (3.7) -42.7  (3.5) -11.2  (5.1) -12.9  (5.2) -31.4  (5.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rosuvastatin 20 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification).
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -31.4
Confidence Interval (2-Sided) 98.75%
-43.9 to -18.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg + Rosuvastatin 10 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Analysis description as per the statistical analysis 1 of this endpoint.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -29.3
Confidence Interval (2-Sided) 98.75%
-42.1 to -16.4
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis
Hide Description Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule [whatever rosuvastatin or ezetimibe], whichever came first).
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed: participants of the mITT population with one baseline and at least one post-baseline Non-HDL-C value on-treatment.
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description:
Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Overall Number of Participants Analyzed 48 46 48 50 50 51
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-12.9  (2.8) -17.5  (3.1) -45.7  (2.9) -14.9  (4.2) -18.2  (4.2) -35.6  (4.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rosuvastatin 20 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification).
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -32.8
Confidence Interval (2-Sided) 98.75%
-43.2 to -22.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg + Rosuvastatin 10 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Analysis description as per the statistical analysis 1 of this endpoint.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -28.2
Confidence Interval (2-Sided) 98.75%
-39.1 to -17.3
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline Total-C value on- or off-treatment.
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description:
Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Overall Number of Participants Analyzed 48 47 48 52 50 53
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-8.3  (2.4) -8.7  (2.6) -28.9  (2.5) -8.5  (3.6) -12.4  (3.6) -20.6  (3.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rosuvastatin 20 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification).
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -20.6
Confidence Interval (2-Sided) 98.75%
-29.4 to -11.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg + Rosuvastatin 10 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Analysis description as per the statistical analysis 1 of this endpoint.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -20.3
Confidence Interval (2-Sided) 98.75%
-29.3 to -11.2
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Percent Change From Baseline in Apo B at Week 12 - ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Apo B ITT population.
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description:
Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Overall Number of Participants Analyzed 44 44 44 51 48 49
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-8.1  (3.2) -12.1  (3.3) -36.1  (3.2) -13.7  (3.3) -14.3  (3.3) -29.0  (3.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rosuvastatin 20 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification).
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -28.1
Confidence Interval (2-Sided) 98.75%
-39.7 to -16.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg + Rosuvastatin 10 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Analysis description as per the statistical analysis 1 of this endpoint.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -24.0
Confidence Interval (2-Sided) 98.75%
-35.7 to -12.3
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Non-HDL-C ITT population.
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description:
Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Overall Number of Participants Analyzed 48 47 48 52 50 53
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-11.7  (3.5) -16.3  (3.6) -41.2  (3.5) -18.0  (3.6) -18.7  (3.7) -29.8  (3.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rosuvastatin 20 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification).
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -29.5
Confidence Interval (2-Sided) 98.75%
-42.1 to -16.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg + Rosuvastatin 10 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Analysis description as per the statistical analysis 1 of this endpoint.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -24.9
Confidence Interval (2-Sided) 98.75%
-37.7 to -12.2
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Percent Change From Baseline in Total-C at Week 12 - ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Total-C ITT population.
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/ up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description:
Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants, who were receiving rosuvastatin 20 mg over-encapsulated tablet orally at baseline, received alirocumab 75 mg Q2W SC injection, rosuvastatin 20 mg over-encapsulated tablet orally QD, and placebo for ezetimibe over-encapsulated tablet orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Overall Number of Participants Analyzed 48 47 48 52 50 53
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-8.9  (2.6) -11.8  (2.7) -29.0  (2.6) -13.8  (2.8) -13.9  (2.8) -19.4  (2.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rosuvastatin 20 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification).
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -20.1
Confidence Interval (2-Sided) 98.75%
-29.4 to -10.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg + Rosuvastatin 10 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Analysis description as per the statistical analysis 1 of this endpoint.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -17.2
Confidence Interval (2-Sided) 98.75%
-26.7 to -7.7
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis
Hide Description Calculated LDL-C values were obtained from Friedewald formula. Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to week 24 regardless of status on- or off-treatment were included in the imputation model (ITT analysis).
Time Frame Up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description:
Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Overall Number of Participants Analyzed 48 47 48 52 50 53
Measure Type: Number
Unit of Measure: percentage of participants
45.0 57.2 84.9 40.1 52.2 66.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rosuvastatin 20 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification). Statistical analysis used a multiple imputation approach followed by a Logistic regression model.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 12.4
Confidence Interval (2-Sided) 98.75%
2.6 to 59.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg + Rosuvastatin 10 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Analysis description as per the statistical analysis 1 of this endpoint.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0007
Comments Threshold for significance ≤ 0.0125.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 8.4
Confidence Interval (2-Sided) 98.75%
1.8 to 40.5
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis
Hide Description Calculated LDL-C values were obtained from Friedewald formula. Adjusted percentages at Week 24 were obtained from a multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 i.e. up to 21 days after last injection or 3 days after the last capsule [whatever rosuvastatin or ezetimibe], whichever came first (on-treatment analysis).
Time Frame Up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description:
Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Overall Number of Participants Analyzed 48 46 48 50 50 51
Measure Type: Number
Unit of Measure: percentage of participants
47.0 60.5 86.4 41.3 54.8 70.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rosuvastatin 20 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification). Statistical analysis used a multiple imputation approach followed by a Logistic regression model.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 15.6
Confidence Interval (2-Sided) 98.75%
2.58 to 88.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg + Rosuvastatin 10 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Analysis description as per the statistical analysis 1 of this endpoint.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.001
Comments Threshold for significance ≤ 0.0125.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 9.9
Confidence Interval (2-Sided) 98.75%
1.7 to 56.7
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis
Hide Description Calculated LDL-C values were obtained from Friedewald formula. Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to week 24 regardless of status on- or off-treatment were included in the imputation model (ITT analysis).
Time Frame Up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description:
Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Overall Number of Participants Analyzed 48 47 48 52 50 53
Measure Type: Number
Unit of Measure: percentage of participants
31.3 43.1 77.8 29.9 43.6 60.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rosuvastatin 20 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification). Statistical analysis used a multiple imputation approach followed by a Logistic regression model.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 18.6
Confidence Interval (2-Sided) 98.75%
3.6 to 96.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg + Rosuvastatin 10 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Analysis description as per the statistical analysis 1 of this endpoint.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 11.6
Confidence Interval (2-Sided) 98.75%
2.5 to 53.1
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis
Hide Description Calculated LDL-C values were obtained from Friedewald formula. Adjusted percentages at Week 24 were obtained from a multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 i.e. up to 21 days after last injection or 3 days after the last capsule [whatever rosuvastatin or ezetimibe], whichever came first (on-treatment analysis).
Time Frame Up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description:
Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Overall Number of Participants Analyzed 48 46 48 50 50 51
Measure Type: Number
Unit of Measure: percentage of participants
34.8 46.7 76.5 30.6 45.1 66.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rosuvastatin 20 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification). Statistical analysis used a multiple imputation approach followed by a Logistic regression model.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 20.3
Confidence Interval (2-Sided) 98.75%
2.4 to 67.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg + Rosuvastatin 10 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Analysis description as per the statistical analysis 1 of this endpoint.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0002
Comments Threshold for significance ≤ 0.0125.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 12.7
Confidence Interval (2-Sided) 98.75%
2.4 to 67.7
Estimation Comments [Not Specified]
17.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 model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed: participants of the ITT population.
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/ up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description:
Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants, who were receiving rosuvastatin 20 mg over-encapsulated tablet orally at baseline, received alirocumab 75 mg Q2W SC injection, rosuvastatin 20 mg over-encapsulated tablet orally QD, and placebo for ezetimibe over-encapsulated tablet orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Overall Number of Participants Analyzed 48 47 48 52 50 53
Mean (Standard Error)
Unit of Measure: percent change
-4.0  (4.3) -4.3  (4.5) -27.9  (4.1) -5.2  (4.8) -5.8  (4.6) -22.7  (5.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rosuvastatin 20 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification). Statistical analysis used a multiple imputation approach followed by a robust regression model.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.0125.
Method Regression, Robust
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -23.9
Confidence Interval (2-Sided) 98.75%
-38.6 to -9.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ezetimibe 10 mg + Rosuvastatin 10 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Analysis description as per the statistical analysis 1 of this endpoint.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0001
Comments Threshold for significance ≤ 0.0125.
Method Regression, Robust
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -23.6
Confidence Interval (2-Sided) 98.75%
-39.0 to -8.2
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline HDL-C value on- or off-treatment.
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description:
Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Overall Number of Participants Analyzed 48 47 48 52 50 53
Least Squares Mean (Standard Error)
Unit of Measure: percent change
1.7  (2.4) 4.0  (2.5) 9.1  (2.4) 1.5  (2.3) -1.8  (2.3) 7.2  (2.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rosuvastatin 20 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
Comments Testing according to the hierarchical testing procedure (previous endpoints were statistically significant for rosuvastatin 10 mg baseline stratification). Statistical analysis used a multiple imputation approach followed by a robust regression model.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0311
Comments Threshold for significance ≤ 0.0125.
Method Regression, Robust
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 7.4
Confidence Interval (2-Sided) 98.75%
-1.2 to 16.1
Estimation Comments [Not Specified]
19.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 model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed: participants of the ITT population.
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description:
Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Overall Number of Participants Analyzed 48 47 48 52 50 53
Mean (Standard Error)
Unit of Measure: percent change
-1.8  (4.5) -8.3  (4.8) -11.2  (4.6) -9.9  (4.1) -11.1  (4.3) -8.7  (4.5)
20.Secondary Outcome
Title Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline Apo A-1 value on- or off-treatment.
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description:
Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Overall Number of Participants Analyzed 44 44 44 51 48 49
Least Squares Mean (Standard Error)
Unit of Measure: percent change
5.4  (1.9) 5.0  (1.9) 6.7  (1.9) 2.9  (1.9) -0.9  (1.9) 6.7  (2.0)
21.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 model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Lipoprotein (a) ITT population.
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description:
Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Overall Number of Participants Analyzed 48 47 48 52 50 53
Mean (Standard Error)
Unit of Measure: percent change
-0.7  (3.5) -3.9  (3.6) -20.7  (3.5) 3.5  (4.2) 7.9  (4.1) -16.0  (4.2)
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 model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
HDL-C ITT population.
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description:
Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Overall Number of Participants Analyzed 48 47 48 52 50 53
Least Squares Mean (Standard Error)
Unit of Measure: percent change
0.7  (2.1) 0.2  (2.2) 5.9  (2.1) 0.6  (2.5) 3.1  (2.5) 8.0  (2.5)
23.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 model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Fasting triglycerides ITT population.
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description:
Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Overall Number of Participants Analyzed 48 47 48 52 50 53
Mean (Standard Error)
Unit of Measure: percent change
8.1  (4.1) -8.2  (4.2) -14  (4.1) -2.7  (4.0) -12.4  (4.0) -10.1  (4.0)
24.Secondary Outcome
Title Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Apo A-1 ITT population.
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description:
Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks.
Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Overall Number of Participants Analyzed 44 44 44 51 48 49
Least Squares Mean (Standard Error)
Unit of Measure: percent change
4.0  (1.6) 2.6  (1.6) 4.3  (1.6) 0.9  (1.8) 1.8  (1.8) 9.1  (1.8)
Time Frame From Baseline to Week 32
Adverse Event Reporting Description Treatment emergent adverse events that developed during on-treatment period (the time period from the first double-blind injection of study drug up to the day of last injection + 70 days) are reported.
 
Arm/Group Title Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Hide Arm/Group Description Participants who were receiving rosuvastatin 10 mg at baseline, received rosuvastatin 20 mg once daily (QD), placebo for alirocumab every 2 weeks (Q2W), and placebo for ezetimibe QD added to stable lipid-modifying therapy (LMT) for 24 weeks. Participants who were receiving rosuvastatin 10 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 10 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks. Participants who were receiving rosuvastatin 10 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 10 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history. Participants who were receiving rosuvastatin 20 mg at baseline, received rosuvastatin 40 mg QD, placebo for alirocumab Q2W, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Participants who were receiving rosuvastatin 20 mg at baseline, received ezetimibe 10 mg QD, rosuvastatin 20 mg QD, and placebo for alirocumab Q2W added to stable LMT for 24 weeks. Participants who were receiving rosuvastatin 20 mg at baseline, received alirocumab 75 mg Q2W, rosuvastatin 20 mg QD, and placebo for ezetimibe QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
All-Cause Mortality
Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--    
Hide Serious Adverse Events
Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/48 (8.33%)      5/48 (10.42%)      2/49 (4.08%)      4/53 (7.55%)      3/53 (5.66%)      4/54 (7.41%)    
Blood and lymphatic system disorders             
Iron deficiency anaemia  1  0/48 (0.00%)  0 0/48 (0.00%)  0 0/49 (0.00%)  0 1/53 (1.89%)  1 0/53 (0.00%)  0 0/54 (0.00%)  0
Thrombotic thrombocytopenic purpura  1  0/48 (0.00%)  0 0/48 (0.00%)  0 0/49 (0.00%)  0 1/53 (1.89%)  1 0/53 (0.00%)  0 0/54 (0.00%)  0
Cardiac disorders             
Acute myocardial infarction  1  0/48 (0.00%)  0 0/48 (0.00%)  0 0/49 (0.00%)  0 0/53 (0.00%)  0 1/53 (1.89%)  1 0/54 (0.00%)  0
Angina unstable  1  0/48 (0.00%)  0 0/48 (0.00%)  0 0/49 (0.00%)  0 0/53 (0.00%)  0 0/53 (0.00%)  0 1/54 (1.85%)  1
Arrhythmia  1  0/48 (0.00%)  0 0/48 (0.00%)  0 0/49 (0.00%)  0 0/53 (0.00%)  0 0/53 (0.00%)  0 1/54 (1.85%)  1
Atrioventricular block second degree  1  0/48 (0.00%)  0 0/48 (0.00%)  0 0/49 (0.00%)  0 1/53 (1.89%)  1 0/53 (0.00%)  0 0/54 (0.00%)  0
Cardiac failure congestive  1  1/48 (2.08%)  1 0/48 (0.00%)  0 0/49 (0.00%)  0 0/53 (0.00%)  0 0/53 (0.00%)  0 0/54 (0.00%)  0
Gastrointestinal disorders             
Upper gastrointestinal haemorrhage  1  0/48 (0.00%)  0 0/48 (0.00%)  0 0/49 (0.00%)  0 0/53 (0.00%)  0 1/53 (1.89%)  1 0/54 (0.00%)  0
General disorders             
Non-Cardiac chest pain  1  0/48 (0.00%)  0 0/48 (0.00%)  0 0/49 (0.00%)  0 1/53 (1.89%)  1 0/53 (0.00%)  0 0/54 (0.00%)  0
Infections and infestations             
Spinal cord infection  1  0/48 (0.00%)  0 1/48 (2.08%)  1 0/49 (0.00%)  0 0/53 (0.00%)  0 0/53 (0.00%)  0 0/54 (0.00%)  0
Urosepsis  1  0/48 (0.00%)  0 0/48 (0.00%)  0 1/49 (2.04%)  1 0/53 (0.00%)  0 0/53 (0.00%)  0 0/54 (0.00%)  0
Viral infection  1  0/48 (0.00%)  0 0/48 (0.00%)  0 1/49 (2.04%)  1 0/53 (0.00%)  0 0/53 (0.00%)  0 0/54 (0.00%)  0
Injury, poisoning and procedural complications             
Accidental overdose  1  0/48 (0.00%)  0 0/48 (0.00%)  0 1/49 (2.04%)  1 0/53 (0.00%)  0 0/53 (0.00%)  0 0/54 (0.00%)  0
Subdural haematoma  1  0/48 (0.00%)  0 0/48 (0.00%)  0 0/49 (0.00%)  0 0/53 (0.00%)  0 1/53 (1.89%)  1 0/54 (0.00%)  0
Toxicity to various agents  1  0/48 (0.00%)  0 0/48 (0.00%)  0 1/49 (2.04%)  1 0/53 (0.00%)  0 0/53 (0.00%)  0 0/54 (0.00%)  0
Metabolism and nutrition disorders             
Obesity  1  1/48 (2.08%)  1 0/48 (0.00%)  0 0/49 (0.00%)  0 0/53 (0.00%)  0 0/53 (0.00%)  0 0/54 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Non-Small cell lung cancer metastatic  1  0/48 (0.00%)  0 1/48 (2.08%)  1 0/49 (0.00%)  0 0/53 (0.00%)  0 0/53 (0.00%)  0 0/54 (0.00%)  0
Prostate cancer  1  1/48 (2.08%)  1 0/48 (0.00%)  0 0/49 (0.00%)  0 0/53 (0.00%)  0 0/53 (0.00%)  0 0/54 (0.00%)  0
Renal cell carcinoma  1  1/48 (2.08%)  1 0/48 (0.00%)  0 0/49 (0.00%)  0 0/53 (0.00%)  0 0/53 (0.00%)  0 0/54 (0.00%)  0
Nervous system disorders             
Haemorrhagic stroke  1  0/48 (0.00%)  0 0/48 (0.00%)  0 0/49 (0.00%)  0 0/53 (0.00%)  0 1/53 (1.89%)  1 0/54 (0.00%)  0
Paraesthesia  1  0/48 (0.00%)  0 1/48 (2.08%)  1 0/49 (0.00%)  0 0/53 (0.00%)  0 0/53 (0.00%)  0 0/54 (0.00%)  0
Subarachnoid haemorrhage  1  0/48 (0.00%)  0 0/48 (0.00%)  0 0/49 (0.00%)  0 0/53 (0.00%)  0 1/53 (1.89%)  1 0/54 (0.00%)  0
Syncope  1  0/48 (0.00%)  0 1/48 (2.08%)  1 0/49 (0.00%)  0 0/53 (0.00%)  0 0/53 (0.00%)  0 1/54 (1.85%)  1
Psychiatric disorders             
Psychotic disorder  1  0/48 (0.00%)  0 0/48 (0.00%)  0 0/49 (0.00%)  0 0/53 (0.00%)  0 0/53 (0.00%)  0 1/54 (1.85%)  1
Renal and urinary disorders             
Haematuria  1  0/48 (0.00%)  0 1/48 (2.08%)  1 0/49 (0.00%)  0 0/53 (0.00%)  0 0/53 (0.00%)  0 0/54 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Rosuvastatin 20 mg Ezetimibe 10 mg + Rosuvastatin 10 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg Rosuvastatin 40 mg Ezetimibe 10 mg + Rosuvastatin 20 mg Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   11/48 (22.92%)      11/48 (22.92%)      11/49 (22.45%)      20/53 (37.74%)      12/53 (22.64%)      15/54 (27.78%)    
Gastrointestinal disorders             
Nausea  1  1/48 (2.08%)  1 1/48 (2.08%)  3 3/49 (6.12%)  3 1/53 (1.89%)  1 1/53 (1.89%)  1 0/54 (0.00%)  0
Diarrhoea  1  0/48 (0.00%)  0 2/48 (4.17%)  2 0/49 (0.00%)  0 3/53 (5.66%)  3 0/53 (0.00%)  0 2/54 (3.70%)  2
General disorders             
Injection site reaction  1  2/48 (4.17%)  3 0/48 (0.00%)  0 1/49 (2.04%)  1 0/53 (0.00%)  0 0/53 (0.00%)  0 3/54 (5.56%)  5
Infections and infestations             
Nasopharyngitis  1  1/48 (2.08%)  1 2/48 (4.17%)  2 2/49 (4.08%)  2 6/53 (11.32%)  6 3/53 (5.66%)  3 2/54 (3.70%)  2
Upper respiratory tract infection  1  3/48 (6.25%)  3 0/48 (0.00%)  0 2/49 (4.08%)  2 6/53 (11.32%)  7 4/53 (7.55%)  4 4/54 (7.41%)  4
Musculoskeletal and connective tissue disorders             
Arthralgia  1  1/48 (2.08%)  1 0/48 (0.00%)  0 4/49 (8.16%)  4 2/53 (3.77%)  2 1/53 (1.89%)  1 0/54 (0.00%)  0
Myalgia  1  1/48 (2.08%)  2 3/48 (6.25%)  3 0/49 (0.00%)  0 1/53 (1.89%)  1 1/53 (1.89%)  1 4/54 (7.41%)  5
Osteoarthritis  1  1/48 (2.08%)  1 3/48 (6.25%)  3 1/49 (2.04%)  1 0/53 (0.00%)  0 0/53 (0.00%)  0 0/54 (0.00%)  0
Pain in extremity  1  3/48 (6.25%)  3 1/48 (2.08%)  1 2/49 (4.08%)  2 5/53 (9.43%)  5 2/53 (3.77%)  2 0/54 (0.00%)  0
Nervous system disorders             
Dizziness  1  3/48 (6.25%)  4 1/48 (2.08%)  1 1/49 (2.04%)  1 2/53 (3.77%)  2 1/53 (1.89%)  1 2/54 (3.70%)  2
Headache  1  0/48 (0.00%)  0 1/48 (2.08%)  1 0/49 (0.00%)  0 3/53 (5.66%)  4 0/53 (0.00%)  0 0/54 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Not less than 45 days prior to submission for publication or presentation, the Institution shall, or cause the Principal Investigator to, provide the Sponsor with a copy of the Manuscript. The Institution shall consider in good faith any comments from the Sponsor regarding the content, and shall delete Confidential Information upon written request of the Sponsor. At the Sponsor's request, the Institution shall delay publication for an additional 60 days to allow patent applications to be filed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Trial Management
Organization: Regeneron Pharmaceuticals
EMail: clinicaltrials@regeneron.com
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Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01730053    
Other Study ID Numbers: R727-CL-1118
First Submitted: November 9, 2012
First Posted: November 21, 2012
Results First Submitted: July 29, 2015
Results First Posted: October 28, 2015
Last Update Posted: April 7, 2020