Long-term Safety and Tolerability of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in High Cardiovascular Risk Patients With Hypercholesterolemia (ODYSSEY Long Term)

• ClinicalTrials.gov Identifier: NCT01507831
• Recruitment Status: Completed
• First Posted: January 11, 2012
• Results First Posted: December 22, 2015
• Last Update Posted: December 22, 2015
• Sponsor: Sanofi
• Collaborator: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Sanofi

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Hypercholesterolemia
• Interventions: Drug: Placebo (for alirocumab); Drug: Alirocumab; Drug: Lipid-Modifying Therapy (LMT)
• Enrollment: 2341

Participant Flow

Recruitment Details	The study was conducted at 320 centers in 27 countries. Overall, 5144 participants were screened between January 2012 and March 2013, 2801 of whom were screen failures. Screen failures were mainly due to exclusion criteria met. In addition 2 participants received study drug but did not undergo randomization. They were excluded from analysis.
Pre-assignment Details	Randomization was stratified as per diagnosis of heterozygous familial hypercholesterolemia (heFH), prior history of myocardial infarction (MI) or ischemic stroke, intensity of statin treatment and geographic region. Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 1:2 ratio (placebo:alirocumab).

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description	Placebo (for alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable lipid modifying therapy (LMT) for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Period Title: Overall Study
Started	788 [1]	1553 [1]
Treated	788	1550
Completed	595	1113
Not Completed	193	440
Reason Not Completed
Randomized but not treated	0	3
Adverse Event	48	113
Death	6	2
Poor compliance to protocol	38	60
Physician Decision	0	4
Participant moved	5	19
Consent withdrawn by participant	34	72
Related to study drug administration	5	14
Last visit outside protocol visit window	51	143
Selection criteria finally not met	0	1
Site closure	0	3
Potential lost to follow-up	3	0
Other	3	6
[1] Randomized

Baseline Characteristics

Arm/Group Title		Placebo Q2W	Alirocumab 150 mg Q2W	Total
Arm/Group Description		Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.	Total of all reporting groups
Overall Number of Baseline Participants		788	1553	2341
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	788 participants	1553 participants	2341 participants
		60.6 (10.4)	60.4 (10.4)	60.5 (10.4)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	788 participants	1553 participants	2341 participants
	Female	314 39.8%	570 36.7%	884 37.8%
	Male	474 60.2%	983 63.3%	1457 62.2%
Calculated LDL-C in mg/dL [1]; Mean (Standard Deviation); Unit of measure: mg/dL
	Number Analyzed	788 participants	1553 participants	2341 participants
		121.9 (41.4)	122.7 (42.6)	122.4 (42.2)
		[1] Measure Description: Calculated LDL-C in mg/dL from Friedewald formula (LDL-C = Total cholesterol - High-density lipoprotein cholesterol - [Triglyceride/5]).
Calculated LDL-C in mmol/L; Mean (Standard Deviation); Unit of measure: mmol/L
	Number Analyzed	788 participants	1553 participants	2341 participants
		3.157 (1.073)	3.178 (1.102)	3.171 (1.092)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Experienced Adverse Events (AEs)
Description	Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Time Frame	Up to 10 weeks after last study drug administration (maximum of 86 weeks)

Outcome Measure Data

Analysis Population Description

Safety population: all randomized participants who received at least one dose or part of a dose of a study drug (treated).

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	788	1550
Measure Type: Number; Unit of Measure: percentage of participants
Any AE	82.5	81.0
Any Serious AE	19.5	18.7
Any AE leading to death	1.3	0.5
Any AE leading to treatment discontinuation	5.8	7.2

2. Secondary Outcome

Title	Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis
Description	Adjusted least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment were used in the model (ITT analysis).
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment.

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	780	1530
Least Squares Mean (Standard Error); Unit of Measure: percent change
	0.8 (1.0)	-61.0 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q2W
	Comments	Alirocumab group was compared to placebo group using an appropriate contrast statement.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-61.9
	Confidence Interval	(2-Sided) 95%; -64.3 to -59.4
	Estimation Comments	Alirocumab vs. Placebo

3. Secondary Outcome

Title	Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis
Description	Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection) (on-treatment analysis).
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Modified ITT (mITT) population: all randomized and treated participants with one baseline and at least one post-baseline calculated LDL-C value on-treatment.

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	777	1523
Least Squares Mean (Standard Error); Unit of Measure: percent change
	0.7 (1.0)	-62.8 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q2W
	Comments	A hierarchial 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 hierarchial testing sequence continued only when previous endpoint was statistically significant at 0.05 level.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-63.5
	Confidence Interval	(2-Sided) 95%; -65.9 to -61.2
	Estimation Comments	Alirocumab vs. Placebo

4. Secondary Outcome

Title	Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	780	1530
Least Squares Mean (Standard Error); Unit of Measure: percent change
	1.5 (1.0)	-63.3 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-64.8
	Confidence Interval	(2-Sided) 95%; -67.2 to -62.4
	Estimation Comments	Alirocumab vs. Placebo

5. Secondary Outcome

Title	Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis
Description	Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection).
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	777	1523
Least Squares Mean (Standard Error); Unit of Measure: percent change
	1.4 (1.0)	-64.2 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-65.5
	Confidence Interval	(2-Sided) 95%; -67.9 to -63.2
	Estimation Comments	Alirocumab vs. Placebo

6. Secondary Outcome

Title	Percent Change From Baseline in Measured LDL-C at Week 24 - ITT Analysis
Description	Measured LDL-C values via beta quantification method. Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Participants of the ITT population with one baseline and at least one post-baseline measured LDL-C value on- or off-treatment.

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	652	1278
Least Squares Mean (Standard Error); Unit of Measure: percent change
	3.5 (1.1)	-57.8 (0.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-61.3
	Confidence Interval	(2-Sided) 95%; -64.0 to -58.5
	Estimation Comments	Alirocumab vs. Placebo

7. Secondary Outcome

Title	Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Participants of the ITT population with one baseline and at least one post-baseline Apo B value on- or off-treatment (Apo B ITT population).

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	753	1468
Least Squares Mean (Standard Error); Unit of Measure: percent change
	1.2 (1.0)	-52.8 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-54.0
	Confidence Interval	(2-Sided) 95%; -56.3 to -51.7
	Estimation Comments	Alirocumab vs. Placebo

8. Secondary Outcome

Title	Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis
Description	Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection).
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Participants of the mITT population with one baseline and at least one post-baseline Apo-B value on-treatment (Apo B mITT population).

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	743	1444
Least Squares Mean (Standard Error); Unit of Measure: percent change
	1.2 (0.9)	-54.3 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-55.5
	Confidence Interval	(2-Sided) 95%; -57.7 to -53.2
	Estimation Comments	Alirocumab vs. Placebo

9. Secondary Outcome

Title	Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Participants of the ITT population with one baseline and at least one post-baseline non-HDL-C value on- or off-treatment (non-HDL-C ITT population).

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	780	1530
Least Squares Mean (Standard Error); Unit of Measure: percent change
	0.7 (0.9)	-51.6 (0.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-52.3
	Confidence Interval	(2-Sided) 95%; -54.4 to -50.2
	Estimation Comments	Alirocumab vs. Placebo

10. Secondary Outcome

Title	Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis
Description	Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection).
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Participants of the mITT population with one baseline and at least one post-baseline non-HDL-C value on-treatment (non-HDL-C mITT population).

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	777	1523
Least Squares Mean (Standard Error); Unit of Measure: percent change
	0.6 (0.9)	-53.1 (0.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-53.7
	Confidence Interval	(2-Sided) 95%; -55.7 to -51.6
	Estimation Comments	Alirocumab vs. Placebo

11. Secondary Outcome

Title	Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Participants of the ITT population with one baseline and at least one post-baseline Total-C value on- or off-treatment (Total-C ITT population).

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	780	1530
Least Squares Mean (Standard Error); Unit of Measure: percent change
	-0.3 (0.7)	-37.8 (0.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-37.5
	Confidence Interval	(2-Sided) 95%; -39.1 to -35.9
	Estimation Comments	Alirocumab vs. Placebo

12. Secondary Outcome

Title	Percent Change From Baseline in Apo B at Week 12 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Apo B ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	753	1468
Least Squares Mean (Standard Error); Unit of Measure: percent change
	0.5 (0.9)	-55.5 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-56.0
	Confidence Interval	(2-Sided) 95%; -58.3 to -53.7
	Estimation Comments	Alirocumab vs. Placebo

13. Secondary Outcome

Title	Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Non-HDL-C ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	780	1530
Least Squares Mean (Standard Error); Unit of Measure: percent change
	0.9 (0.8)	-53.7 (0.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-54.6
	Confidence Interval	(2-Sided) 95%; -56.6 to -52.6
	Estimation Comments	Alirocumab vs. Placebo

14. Secondary Outcome

Title	Percent Change From Baseline in Total-C at Week 12 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Total-C ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	780	1530
Least Squares Mean (Standard Error); Unit of Measure: percent change
	0.2 (0.6)	-38.8 (0.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-39.0
	Confidence Interval	(2-Sided) 95%; -40.4 to -37.5
	Estimation Comments	Alirocumab vs. Placebo

15. Secondary Outcome

Title	Percentage of Very High Cardiovascular (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
Description	Very high CV risk: Heterozygous Familial Hypercholesterolemia (heFH) participants with coronary heart disease (CHD) or CHD risk equivalents or non- Familial Hypercholesterolemia (FH). High CV risk: heFH participants without CHD or CHD risk equivalents. CHD risk equivalent: peripheral arterial disease, ischemic stroke, moderate chronic kidney disease (estimated glomerular filtration rate, 30 to <60 ml/minute/1.73 m^2 of body-surface area), or diabetes mellitus plus 2 or more additional risk factors (hypertension; ankle-brachial index of ≤0.90; microalbuminuria, macroalbuminuria, or a urinary dipstick result of >2+ protein; preproliferative or proliferative retinopathy or laser treatment for retinopathy; or family history of premature CHD). Adjusted percentages at Week 24 were obtained from multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment were included in imputation model.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	780	1530
Measure Type: Number; Unit of Measure: percentage of participants
	8.5	80.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Regression, Logistic
	Comments	Multiple imputation approach followed by logistic regression model.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	71.5
	Confidence Interval	(2-Sided) 95%; 51.6 to 99.1
	Estimation Comments	Alirocumab vs. Placebo

16. 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
Description	Adjusted percentages at Week 24 were from multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection).
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	777	1523
Measure Type: Number; Unit of Measure: percentage of participants
	8.5	82.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Regression, Logistic
	Comments	Multiple imputation approach followed by logistic regression model.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	93.4
	Confidence Interval	(2-Sided) 95%; 66.1 to 132.0
	Estimation Comments	Alirocumab vs. Placebo

17. Secondary Outcome

Title	Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis
Description	Adjusted percentages at Week 24 were obtained from multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment were included in the imputation model.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	780	1530
Measure Type: Number; Unit of Measure: percentage of participants
	8.0	79.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Regression, Logistic
	Comments	Multiple imputation approach followed by logistic regression model.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	74.6
	Confidence Interval	(2-Sided) 95%; 53.3 to 104.4
	Estimation Comments	Alirocumab vs. Placebo

18. Secondary Outcome

Title	Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis
Description	Adjusted percentages at Week 24 from multiple imputation approach model including available post-baseline data from Week 4 to Week 52 (i.e. up to 21 days after last injection).
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	777	1523
Measure Type: Number; Unit of Measure: percentage of participants
	8.0	81.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Regression, Logistic
	Comments	Multiple imputation approach followed by logistic regression model.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	97.3
	Confidence Interval	(2-Sided) 95%; 68.2 to 138.9
	Estimation Comments	Alirocumab vs. Placebo

19. Secondary Outcome

Title	Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis
Description	Adjusted means and standard errors at Week 24 were obtained from multiple imputation approach followed by robust regression model for handling of missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment were included in the imputation model.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	780	1530
Mean (Standard Error); Unit of Measure: percent change
	-3.7 (1.0)	-29.3 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Regression, Robust
	Comments	Multiple imputation approach followed by a robust regression model.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-25.6
	Confidence Interval	(2-Sided) 95%; -28.1 to -23.1
	Estimation Comments	Alirocumab vs. Placebo

20. Secondary Outcome

Title	Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Participants of the ITT population with one baseline and at least one post-baseline HDL-C value on- or off-treatment (HDL-C ITT population).

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	780	1530
Least Squares Mean (Standard Error); Unit of Measure: percent change
	-0.6 (0.5)	4.0 (0.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.6
	Confidence Interval	(2-Sided) 95%; 3.3 to 5.9
	Estimation Comments	Alirocumab vs. Placebo

21. Secondary Outcome

Title	Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
Description	Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	780	1530
Mean (Standard Error); Unit of Measure: percent change
	1.8 (1.2)	-15.6 (0.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Regression, Robust
	Comments	Multiple imputation approach followed by a robust regression model.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-17.3
	Confidence Interval	(2-Sided) 95%; -20.1 to -14.6
	Estimation Comments	Alirocumab vs. Placebo

22. Secondary Outcome

Title	Percent Change From Baseline in Apo A1 at Week 24 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Participants of the ITT population with one baseline and at least one post-baseline Apo A1 value on- or off-treatment (Apo A1 ITT population).

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	753	1468
Least Squares Mean (Standard Error); Unit of Measure: percent change
	1.2 (0.6)	4.0 (0.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.9
	Confidence Interval	(2-Sided) 95%; 1.6 to 4.2
	Estimation Comments	Alirocumab vs. Placebo

23. Secondary Outcome

Title	Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis
Description	Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	780	1530
Mean (Standard Error); Unit of Measure: percent change
	-3.1 (1.0)	-28.2 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Regression, Robust
	Comments	Multiple imputation approach followed by a robust regression model.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-25.1
	Confidence Interval	(2-Sided) 95%; -27.4 to -22.7
	Estimation Comments	Alirocumab vs. Placebo

24. Secondary Outcome

Title	Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

HDL-C ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	780	1530
Least Squares Mean (Standard Error); Unit of Measure: percent change
	0.2 (0.5)	5.8 (0.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	5.6
	Confidence Interval	(2-Sided) 95%; 4.3 to 6.8
	Estimation Comments	Alirocumab vs. Placebo

25. Secondary Outcome

Title	Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis
Description	Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	780	1530
Mean (Standard Error); Unit of Measure: percent change
	1.2 (1.1)	-16.7 (0.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Regression, Robust
	Comments	Multiple imputation approach followed by a robust regression model.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-17.9
	Confidence Interval	(2-Sided) 95%; -20.5 to -15.3
	Estimation Comments	Alirocumab vs. Placebo

26. Secondary Outcome

Title	Percent Change From Baseline in Apo A1 at Week 12 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Apo A1 ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	753	1468
Least Squares Mean (Standard Error); Unit of Measure: percent change
	0.6 (0.5)	4.6 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.0
	Confidence Interval	(2-Sided) 95%; 2.8 to 5.2
	Estimation Comments	Alirocumab vs. Placebo

27. Other Pre-specified Outcome

Title	Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 52 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	780	1530
Least Squares Mean (Standard Error); Unit of Measure: percent change
	4.4 (1.2)	-56.8 (0.8)

28. Other Pre-specified Outcome

Title	Percent Change From Baseline in Calculated LDL-C at Week 52 - On-Treatment Analysis
Description	Adjusted LS means and standard errors at Week 52 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection).
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	777	1523
Least Squares Mean (Standard Error); Unit of Measure: percent change
	4.6 (1.1)	-59.9 (0.8)

29. Other Pre-specified Outcome

Title	Percent Change From Baseline in Calculated LDL-C at Week 78 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 78 from MMRM model including all available post-baseline data from Week 4 to Week 78 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 78

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	780	1530
Least Squares Mean (Standard Error); Unit of Measure: percent change
	3.6 (1.3)	-52.4 (0.9)

30. Other Pre-specified Outcome

Title	Percent Change From Baseline in Calculated LDL-C at Week 78 - On-Treatment Analysis
Description	Adjusted LS means and standard errors at Week 78 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 78 (i.e. up to 21 days after last injection).
Time Frame	From Baseline to Week 78

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	777	1523
Least Squares Mean (Standard Error); Unit of Measure: percent change
	3.9 (1.2)	-58.0 (0.9)

31. Other Pre-specified Outcome

Title	Percentage of Participants Who Experienced Cardiovascular (CV) Events
Description	CV events included coronary heart disease (CHD) death; non-fatal myocardial infarction (MI); fatal and non-fatal ischemic stroke; unstable angina requiring hospitalization; congestive heart failure (CHF) requiring hospitalization; ischemia-driven coronary revascularization procedure. Reported events are CV events as confirmed by an independent Clinical Events Committee (CEC) that occurred during the treatment emergent period ( i.e. from first dose up to the last dose of study drug + 70 days).
Time Frame	Up to 10 weeks after last study drug administration (maximum of 86 weeks)

Outcome Measure Data

Analysis Population Description

Safety population.

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	788	1550
Measure Type: Number; Unit of Measure: percentage of participants
	5.1	4.6

32. Post-Hoc Outcome

Title	Percentage of Participants Who Experienced Major Adverse CV Events
Description	Major adverse CV events were defined as all adverse CV events except Congestive heart failure (CHF) requiring hospitalization; and ischemia-driven coronary revascularization procedure.
Time Frame	Up to 10 weeks after last study drug administration (maximum of 86 weeks)

Outcome Measure Data

Analysis Population Description

Safety population.

Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Number of Participants Analyzed	788	1550
Measure Type: Number; Unit of Measure: percentage of participants
	3.3	1.7

Adverse Events

Time Frame	All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 86 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description	Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Arm/Group Title	Placebo Q2W	Alirocumab 150 mg Q2W
Arm/Group Description	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
All-Cause Mortality
	Placebo Q2W	Alirocumab 150 mg Q2W
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Placebo Q2W	Alirocumab 150 mg Q2W
	Affected / at Risk (%)	Affected / at Risk (%)
Total	154/788 (19.54%)	290/1550 (18.71%)
Blood and lymphatic system disorders
Iron deficiency anaemia † 1	0/788 (0.00%)	1/1550 (0.06%)
Coagulopathy † 1	0/788 (0.00%)	1/1550 (0.06%)
Spontaneous haematoma † 1	1/788 (0.13%)	0/1550 (0.00%)
Cardiac disorders
Angina unstable † 1	9/788 (1.14%)	29/1550 (1.87%)
Angina pectoris † 1	6/788 (0.76%)	9/1550 (0.58%)
Atrial fibrillation † 1	7/788 (0.89%)	9/1550 (0.58%)
Cardiac failure † 1	3/788 (0.38%)	4/1550 (0.26%)
Coronary artery disease † 1	3/788 (0.38%)	10/1550 (0.65%)
Acute myocardial infarction † 1	11/788 (1.40%)	9/1550 (0.58%)
Bradycardia † 1	0/788 (0.00%)	2/1550 (0.13%)
Myocardial ischaemia † 1	2/788 (0.25%)	3/1550 (0.19%)
Cardiac failure chronic † 1	0/788 (0.00%)	2/1550 (0.13%)
Atrial flutter † 1	1/788 (0.13%)	2/1550 (0.13%)
Cardiac failure congestive † 1	3/788 (0.38%)	4/1550 (0.26%)
Myocardial infarction † 1	4/788 (0.51%)	4/1550 (0.26%)
Ventricular tachycardia † 1	1/788 (0.13%)	2/1550 (0.13%)
Cardiac arrest † 1	0/788 (0.00%)	3/1550 (0.19%)
Ischaemic cardiomyopathy † 1	1/788 (0.13%)	2/1550 (0.13%)
Supraventricular tachycardia † 1	0/788 (0.00%)	1/1550 (0.06%)
Acute coronary syndrome † 1	6/788 (0.76%)	2/1550 (0.13%)
Aortic valve stenosis † 1	1/788 (0.13%)	2/1550 (0.13%)
Arteriosclerosis coronary artery † 1	0/788 (0.00%)	1/1550 (0.06%)
Atrioventricular block second degree † 1	0/788 (0.00%)	1/1550 (0.06%)
Coronary artery stenosis † 1	2/788 (0.25%)	2/1550 (0.13%)
Sinus bradycardia † 1	0/788 (0.00%)	1/1550 (0.06%)
Atrioventricular block † 1	0/788 (0.00%)	1/1550 (0.06%)
Extrasystoles † 1	1/788 (0.13%)	0/1550 (0.00%)
Hypertensive heart disease † 1	0/788 (0.00%)	1/1550 (0.06%)
Sick sinus syndrome † 1	1/788 (0.13%)	1/1550 (0.06%)
Silent myocardial infarction † 1	0/788 (0.00%)	1/1550 (0.06%)
Ventricular fibrillation † 1	2/788 (0.25%)	1/1550 (0.06%)
Cardiogenic shock † 1	1/788 (0.13%)	0/1550 (0.00%)
Coronary artery occlusion † 1	1/788 (0.13%)	0/1550 (0.00%)
Dressler's syndrome † 1	1/788 (0.13%)	0/1550 (0.00%)
Pleuropericarditis † 1	1/788 (0.13%)	0/1550 (0.00%)
Congenital, familial and genetic disorders
Hypertrophic cardiomyopathy † 1	1/788 (0.13%)	0/1550 (0.00%)
Thyroglossal cyst † 1	1/788 (0.13%)	0/1550 (0.00%)
Ear and labyrinth disorders
Vertigo † 1	0/788 (0.00%)	1/1550 (0.06%)
Vertigo positional † 1	1/788 (0.13%)	0/1550 (0.00%)
Endocrine disorders
Thyrotoxic crisis † 1	0/788 (0.00%)	1/1550 (0.06%)
Eye disorders
Cataract † 1	1/788 (0.13%)	1/1550 (0.06%)
Diabetic retinopathy † 1	1/788 (0.13%)	0/1550 (0.00%)
Vitreous detachment † 1	0/788 (0.00%)	1/1550 (0.06%)
Visual impairment † 1	0/788 (0.00%)	1/1550 (0.06%)
Age-related macular degeneration † 1	0/788 (0.00%)	1/1550 (0.06%)
Retinal haemorrhage † 1	0/788 (0.00%)	1/1550 (0.06%)
Endocrine ophthalmopathy † 1	0/788 (0.00%)	1/1550 (0.06%)
Macular hole † 1	0/788 (0.00%)	1/1550 (0.06%)
Open angle glaucoma † 1	0/788 (0.00%)	1/1550 (0.06%)
Retinal vein thrombosis † 1	0/788 (0.00%)	1/1550 (0.06%)
Blepharochalasis † 1	1/788 (0.13%)	0/1550 (0.00%)
Retinal artery occlusion † 1	1/788 (0.13%)	0/1550 (0.00%)
Retinal vein occlusion † 1	2/788 (0.25%)	0/1550 (0.00%)
Gastrointestinal disorders
Diarrhoea † 1	0/788 (0.00%)	1/1550 (0.06%)
Nausea † 1	1/788 (0.13%)	0/1550 (0.00%)
Vomiting † 1	1/788 (0.13%)	0/1550 (0.00%)
Abdominal pain † 1	1/788 (0.13%)	3/1550 (0.19%)
Dyspepsia † 1	1/788 (0.13%)	0/1550 (0.00%)
Gastritis † 1	2/788 (0.25%)	1/1550 (0.06%)
Haemorrhoids † 1	0/788 (0.00%)	1/1550 (0.06%)
Hiatus hernia † 1	0/788 (0.00%)	1/1550 (0.06%)
Large intestine polyp † 1	0/788 (0.00%)	1/1550 (0.06%)
Barrett's oesophagus † 1	1/788 (0.13%)	1/1550 (0.06%)
Abdominal hernia † 1	1/788 (0.13%)	1/1550 (0.06%)
Umbilical hernia † 1	0/788 (0.00%)	1/1550 (0.06%)
Abdominal adhesions † 1	0/788 (0.00%)	1/1550 (0.06%)
Colitis † 1	3/788 (0.38%)	1/1550 (0.06%)
Diverticulum intestinal † 1	1/788 (0.13%)	0/1550 (0.00%)
Duodenal ulcer haemorrhage † 1	1/788 (0.13%)	1/1550 (0.06%)
Gastroduodenal haemorrhage † 1	0/788 (0.00%)	1/1550 (0.06%)
Intestinal obstruction † 1	0/788 (0.00%)	1/1550 (0.06%)
Intestinal perforation † 1	0/788 (0.00%)	1/1550 (0.06%)
Pancreatitis † 1	0/788 (0.00%)	1/1550 (0.06%)
Pancreatitis acute † 1	0/788 (0.00%)	1/1550 (0.06%)
Pancreatitis relapsing † 1	0/788 (0.00%)	1/1550 (0.06%)
Peptic ulcer haemorrhage † 1	0/788 (0.00%)	1/1550 (0.06%)
Abdominal hernia obstructive † 1	1/788 (0.13%)	0/1550 (0.00%)
Alcoholic pancreatitis † 1	1/788 (0.13%)	0/1550 (0.00%)
Intussusception † 1	1/788 (0.13%)	0/1550 (0.00%)
Pancreatitis chronic † 1	1/788 (0.13%)	0/1550 (0.00%)
Upper gastrointestinal haemorrhage † 1	1/788 (0.13%)	0/1550 (0.00%)
General disorders
Non-cardiac chest pain † 1	2/788 (0.25%)	13/1550 (0.84%)
Chest pain † 1	1/788 (0.13%)	0/1550 (0.00%)
Coronary artery restenosis † 1	1/788 (0.13%)	1/1550 (0.06%)
Device failure † 1	0/788 (0.00%)	1/1550 (0.06%)
Multi-organ failure † 1	4/788 (0.51%)	1/1550 (0.06%)
Peripheral artery restenosis † 1	0/788 (0.00%)	1/1550 (0.06%)
Death † 1	1/788 (0.13%)	0/1550 (0.00%)
Device malfunction † 1	1/788 (0.13%)	0/1550 (0.00%)
Hepatobiliary disorders
Cholelithiasis † 1	0/788 (0.00%)	3/1550 (0.19%)
Hepatic steatosis † 1	1/788 (0.13%)	0/1550 (0.00%)
Cholecystitis † 1	1/788 (0.13%)	1/1550 (0.06%)
Cholecystitis acute † 1	0/788 (0.00%)	2/1550 (0.13%)
Bile duct stone † 1	0/788 (0.00%)	1/1550 (0.06%)
Drug-induced liver injury † 1	1/788 (0.13%)	0/1550 (0.00%)
Hepatocellular injury † 1	0/788 (0.00%)	1/1550 (0.06%)
Cholangitis † 1	1/788 (0.13%)	0/1550 (0.00%)
Immune system disorders
Drug hypersensitivity † 1	0/788 (0.00%)	1/1550 (0.06%)
Hypersensitivity † 1	0/788 (0.00%)	1/1550 (0.06%)
Cytokine release syndrome † 1	1/788 (0.13%)	0/1550 (0.00%)
Infections and infestations
Upper respiratory tract infection † 1	0/788 (0.00%)	1/1550 (0.06%)
Urinary tract infection † 1	0/788 (0.00%)	3/1550 (0.19%)
Influenza † 1	2/788 (0.25%)	0/1550 (0.00%)
Bronchitis † 1	1/788 (0.13%)	0/1550 (0.00%)
Lower respiratory tract infection † 1	1/788 (0.13%)	2/1550 (0.13%)
Gastroenteritis † 1	2/788 (0.25%)	5/1550 (0.32%)
Pneumonia † 1	7/788 (0.89%)	6/1550 (0.39%)
Cellulitis † 1	1/788 (0.13%)	3/1550 (0.19%)
Gastroenteritis viral † 1	0/788 (0.00%)	2/1550 (0.13%)
Pyelonephritis † 1	0/788 (0.00%)	3/1550 (0.19%)
Diverticulitis † 1	0/788 (0.00%)	4/1550 (0.26%)
Sepsis † 1	1/788 (0.13%)	5/1550 (0.32%)
Gastrointestinal viral infection † 1	1/788 (0.13%)	0/1550 (0.00%)
Labyrinthitis † 1	0/788 (0.00%)	1/1550 (0.06%)
Postoperative wound infection † 1	1/788 (0.13%)	0/1550 (0.00%)
Bronchopneumonia † 1	0/788 (0.00%)	1/1550 (0.06%)
Groin abscess † 1	0/788 (0.00%)	1/1550 (0.06%)
Infective exacerbation of chronic obstructive airways disease † 1	0/788 (0.00%)	1/1550 (0.06%)
Osteomyelitis † 1	1/788 (0.13%)	1/1550 (0.06%)
Pneumonia pneumococcal † 1	0/788 (0.00%)	1/1550 (0.06%)
Pyelonephritis acute † 1	0/788 (0.00%)	1/1550 (0.06%)
Device related infection † 1	0/788 (0.00%)	1/1550 (0.06%)
Incision site infection † 1	0/788 (0.00%)	1/1550 (0.06%)
Lobar pneumonia † 1	0/788 (0.00%)	1/1550 (0.06%)
Lyme disease † 1	0/788 (0.00%)	1/1550 (0.06%)
Pneumonia staphylococcal † 1	0/788 (0.00%)	1/1550 (0.06%)
Urinary tract infection pseudomonal † 1	0/788 (0.00%)	1/1550 (0.06%)
Wound abscess † 1	0/788 (0.00%)	1/1550 (0.06%)
Clostridium difficile colitis † 1	1/788 (0.13%)	0/1550 (0.00%)
Cystitis viral † 1	1/788 (0.13%)	0/1550 (0.00%)
Diabetic foot infection † 1	1/788 (0.13%)	0/1550 (0.00%)
Helicobacter gastritis † 1	1/788 (0.13%)	0/1550 (0.00%)
Neutropenic sepsis † 1	1/788 (0.13%)	0/1550 (0.00%)
Post procedural sepsis † 1	1/788 (0.13%)	0/1550 (0.00%)
Septic shock † 1	1/788 (0.13%)	0/1550 (0.00%)
Urosepsis † 1	1/788 (0.13%)	0/1550 (0.00%)
Injury, poisoning and procedural complications
Contusion † 1	0/788 (0.00%)	1/1550 (0.06%)
Laceration † 1	0/788 (0.00%)	1/1550 (0.06%)
Accidental overdose † 1	1/788 (0.13%)	0/1550 (0.00%)
Muscle strain † 1	1/788 (0.13%)	0/1550 (0.00%)
Tendon rupture † 1	0/788 (0.00%)	2/1550 (0.13%)
Joint injury † 1	0/788 (0.00%)	1/1550 (0.06%)
Rib fracture † 1	0/788 (0.00%)	1/1550 (0.06%)
Ankle fracture † 1	0/788 (0.00%)	2/1550 (0.13%)
Hand fracture † 1	0/788 (0.00%)	1/1550 (0.06%)
Traumatic haematoma † 1	0/788 (0.00%)	1/1550 (0.06%)
Wrist fracture † 1	1/788 (0.13%)	0/1550 (0.00%)
Clavicle fracture † 1	1/788 (0.13%)	1/1550 (0.06%)
Intentional overdose † 1	1/788 (0.13%)	2/1550 (0.13%)
Post procedural haematoma † 1	0/788 (0.00%)	1/1550 (0.06%)
Humerus fracture † 1	0/788 (0.00%)	1/1550 (0.06%)
Ligament rupture † 1	2/788 (0.25%)	0/1550 (0.00%)
Abdominal injury † 1	0/788 (0.00%)	1/1550 (0.06%)
Femoral neck fracture † 1	1/788 (0.13%)	1/1550 (0.06%)
Femur fracture † 1	0/788 (0.00%)	1/1550 (0.06%)
Fibula fracture † 1	0/788 (0.00%)	1/1550 (0.06%)
Hip fracture † 1	1/788 (0.13%)	0/1550 (0.00%)
Muscle rupture † 1	1/788 (0.13%)	0/1550 (0.00%)
Post procedural haematuria † 1	0/788 (0.00%)	1/1550 (0.06%)
Tibia fracture † 1	0/788 (0.00%)	1/1550 (0.06%)
Traumatic intracranial haemorrhage † 1	0/788 (0.00%)	1/1550 (0.06%)
Vascular pseudoaneurysm † 1	0/788 (0.00%)	1/1550 (0.06%)
Arterial injury † 1	1/788 (0.13%)	0/1550 (0.00%)
Postoperative respiratory failure † 1	1/788 (0.13%)	0/1550 (0.00%)
Spinal cord injury † 1	1/788 (0.13%)	0/1550 (0.00%)
Investigations
Blood creatine phosphokinase increased † 1	0/788 (0.00%)	1/1550 (0.06%)
Electrocardiogram QT prolonged † 1	1/788 (0.13%)	0/1550 (0.00%)
Troponin increased † 1	1/788 (0.13%)	1/1550 (0.06%)
Electrocardiogram ST segment depression † 1	0/788 (0.00%)	1/1550 (0.06%)
Metabolism and nutrition disorders
Diabetes mellitus † 1	2/788 (0.25%)	2/1550 (0.13%)
Type 2 diabetes mellitus † 1	0/788 (0.00%)	1/1550 (0.06%)
Hypokalaemia † 1	0/788 (0.00%)	1/1550 (0.06%)
Hypoglycaemia † 1	1/788 (0.13%)	3/1550 (0.19%)
Hyperglycaemia † 1	1/788 (0.13%)	2/1550 (0.13%)
Dehydration † 1	0/788 (0.00%)	1/1550 (0.06%)
Hyperkalaemia † 1	0/788 (0.00%)	1/1550 (0.06%)
Lipomatosis † 1	0/788 (0.00%)	1/1550 (0.06%)
Diabetic ketoacidosis † 1	1/788 (0.13%)	0/1550 (0.00%)
Lactic acidosis † 1	1/788 (0.13%)	0/1550 (0.00%)
Tumour lysis syndrome † 1	1/788 (0.13%)	0/1550 (0.00%)
Musculoskeletal and connective tissue disorders
Back pain † 1	1/788 (0.13%)	1/1550 (0.06%)
Arthralgia † 1	0/788 (0.00%)	2/1550 (0.13%)
Osteoarthritis † 1	3/788 (0.38%)	8/1550 (0.52%)
Intervertebral disc protrusion † 1	0/788 (0.00%)	4/1550 (0.26%)
Arthritis † 1	0/788 (0.00%)	2/1550 (0.13%)
Musculoskeletal chest pain † 1	3/788 (0.38%)	2/1550 (0.13%)
Spinal osteoarthritis † 1	1/788 (0.13%)	0/1550 (0.00%)
Rotator cuff syndrome † 1	1/788 (0.13%)	0/1550 (0.00%)
Intervertebral disc degeneration † 1	1/788 (0.13%)	1/1550 (0.06%)
Lumbar spinal stenosis † 1	2/788 (0.25%)	0/1550 (0.00%)
Myositis † 1	0/788 (0.00%)	2/1550 (0.13%)
Osteonecrosis † 1	0/788 (0.00%)	1/1550 (0.06%)
Polymyalgia rheumatica † 1	1/788 (0.13%)	0/1550 (0.00%)
Rhabdomyolysis † 1	0/788 (0.00%)	1/1550 (0.06%)
Spinal column stenosis † 1	0/788 (0.00%)	1/1550 (0.06%)
Vertebral foraminal stenosis † 1	0/788 (0.00%)	1/1550 (0.06%)
Ankylosing spondylitis † 1	1/788 (0.13%)	0/1550 (0.00%)
Osteochondrosis † 1	1/788 (0.13%)	0/1550 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma † 1	2/788 (0.25%)	8/1550 (0.52%)
Prostate cancer † 1	3/788 (0.38%)	3/1550 (0.19%)
Squamous cell carcinoma of skin † 1	0/788 (0.00%)	3/1550 (0.19%)
Colon cancer † 1	0/788 (0.00%)	2/1550 (0.13%)
Squamous cell carcinoma † 1	0/788 (0.00%)	1/1550 (0.06%)
B-cell lymphoma † 1	0/788 (0.00%)	1/1550 (0.06%)
Benign ovarian tumour † 1	0/788 (0.00%)	1/1550 (0.06%)
Breast cancer † 1	1/788 (0.13%)	1/1550 (0.06%)
Laryngeal squamous cell carcinoma † 1	0/788 (0.00%)	1/1550 (0.06%)
Neuroendocrine carcinoma metastatic † 1	0/788 (0.00%)	1/1550 (0.06%)
Non-Hodgkin's lymphoma metastatic † 1	0/788 (0.00%)	1/1550 (0.06%)
Pleomorphic liposarcoma † 1	0/788 (0.00%)	1/1550 (0.06%)
Prostate cancer metastatic † 1	0/788 (0.00%)	1/1550 (0.06%)
Rectal adenocarcinoma † 1	0/788 (0.00%)	1/1550 (0.06%)
Renal cancer † 1	0/788 (0.00%)	1/1550 (0.06%)
Skin cancer † 1	0/788 (0.00%)	1/1550 (0.06%)
Squamous cell carcinoma of the oral cavity † 1	0/788 (0.00%)	1/1550 (0.06%)
Acute myeloid leukaemia † 1	1/788 (0.13%)	0/1550 (0.00%)
Adenocarcinoma of colon † 1	1/788 (0.13%)	0/1550 (0.00%)
Bladder cancer † 1	1/788 (0.13%)	0/1550 (0.00%)
Choroid melanoma † 1	1/788 (0.13%)	0/1550 (0.00%)
Chronic lymphocytic leukaemia † 1	1/788 (0.13%)	0/1550 (0.00%)
Ductal adenocarcinoma of pancreas † 1	1/788 (0.13%)	0/1550 (0.00%)
Endometrial cancer † 1	1/788 (0.13%)	0/1550 (0.00%)
Endometrial cancer stage I † 1	1/788 (0.13%)	0/1550 (0.00%)
Lentigo maligna † 1	1/788 (0.13%)	0/1550 (0.00%)
Lip squamous cell carcinoma † 1	1/788 (0.13%)	0/1550 (0.00%)
Malignant melanoma † 1	1/788 (0.13%)	0/1550 (0.00%)
Oesophageal carcinoma † 1	1/788 (0.13%)	0/1550 (0.00%)
Pancreatic carcinoma † 1	1/788 (0.13%)	0/1550 (0.00%)
Pancreatic carcinoma metastatic † 1	1/788 (0.13%)	0/1550 (0.00%)
Prostate cancer recurrent † 1	1/788 (0.13%)	0/1550 (0.00%)
Squamous cell carcinoma of lung † 1	1/788 (0.13%)	0/1550 (0.00%)
Tongue cancer metastatic † 1	1/788 (0.13%)	0/1550 (0.00%)
Nervous system disorders
Headache † 1	1/788 (0.13%)	2/1550 (0.13%)
Syncope † 1	6/788 (0.76%)	11/1550 (0.71%)
Hypoaesthesia † 1	2/788 (0.25%)	0/1550 (0.00%)
Carpal tunnel syndrome † 1	0/788 (0.00%)	2/1550 (0.13%)
Transient ischaemic attack † 1	0/788 (0.00%)	7/1550 (0.45%)
Presyncope † 1	1/788 (0.13%)	1/1550 (0.06%)
Ischaemic stroke † 1	1/788 (0.13%)	5/1550 (0.32%)
Migraine † 1	1/788 (0.13%)	0/1550 (0.00%)
Carotid artery stenosis † 1	1/788 (0.13%)	2/1550 (0.13%)
Loss of consciousness † 1	0/788 (0.00%)	3/1550 (0.19%)
Carotid arteriosclerosis † 1	1/788 (0.13%)	2/1550 (0.13%)
Cerebrovascular accident † 1	0/788 (0.00%)	2/1550 (0.13%)
Dysarthria † 1	0/788 (0.00%)	1/1550 (0.06%)
Lacunar infarction † 1	0/788 (0.00%)	3/1550 (0.19%)
Haemorrhagic stroke † 1	0/788 (0.00%)	2/1550 (0.13%)
Nerve root compression † 1	0/788 (0.00%)	1/1550 (0.06%)
Ataxia † 1	0/788 (0.00%)	1/1550 (0.06%)
Brain stem infarction † 1	0/788 (0.00%)	1/1550 (0.06%)
Cerebellar infarction † 1	0/788 (0.00%)	1/1550 (0.06%)
Convulsion † 1	0/788 (0.00%)	1/1550 (0.06%)
Dementia † 1	1/788 (0.13%)	1/1550 (0.06%)
Demyelination † 1	0/788 (0.00%)	1/1550 (0.06%)
Frontotemporal dementia † 1	0/788 (0.00%)	1/1550 (0.06%)
Hypoglycaemic coma † 1	0/788 (0.00%)	1/1550 (0.06%)
Miller Fisher syndrome † 1	0/788 (0.00%)	1/1550 (0.06%)
Optic neuritis † 1	0/788 (0.00%)	1/1550 (0.06%)
Parkinson's disease † 1	1/788 (0.13%)	0/1550 (0.00%)
Altered state of consciousness † 1	1/788 (0.13%)	0/1550 (0.00%)
Cerebral haemorrhage † 1	1/788 (0.13%)	0/1550 (0.00%)
Cerebral infarction † 1	1/788 (0.13%)	0/1550 (0.00%)
Generalised tonic-clonic seizure † 1	1/788 (0.13%)	0/1550 (0.00%)
Myoclonic epilepsy † 1	1/788 (0.13%)	0/1550 (0.00%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous † 1	1/788 (0.13%)	0/1550 (0.00%)
Psychiatric disorders
Depression † 1	2/788 (0.25%)	2/1550 (0.13%)
Confusional state † 1	0/788 (0.00%)	1/1550 (0.06%)
Alcohol abuse † 1	1/788 (0.13%)	0/1550 (0.00%)
Panic attack † 1	0/788 (0.00%)	1/1550 (0.06%)
Bipolar disorder † 1	0/788 (0.00%)	2/1550 (0.13%)
Suicidal ideation † 1	0/788 (0.00%)	1/1550 (0.06%)
Suicide attempt † 1	1/788 (0.13%)	2/1550 (0.13%)
Major depression † 1	1/788 (0.13%)	1/1550 (0.06%)
Depression suicidal † 1	1/788 (0.13%)	0/1550 (0.00%)
Mental disorder due to a general medical condition † 1	1/788 (0.13%)	0/1550 (0.00%)
Mental status changes † 1	2/788 (0.25%)	0/1550 (0.00%)
Renal and urinary disorders
Haematuria † 1	1/788 (0.13%)	2/1550 (0.13%)
Nephrolithiasis † 1	1/788 (0.13%)	3/1550 (0.19%)
Renal failure acute † 1	3/788 (0.38%)	2/1550 (0.13%)
Renal failure chronic † 1	0/788 (0.00%)	1/1550 (0.06%)
Renal impairment † 1	1/788 (0.13%)	0/1550 (0.00%)
Urinary retention † 1	1/788 (0.13%)	1/1550 (0.06%)
Calculus ureteric † 1	0/788 (0.00%)	1/1550 (0.06%)
Diabetic nephropathy † 1	0/788 (0.00%)	1/1550 (0.06%)
Renal pain † 1	0/788 (0.00%)	1/1550 (0.06%)
Urethral stenosis † 1	0/788 (0.00%)	2/1550 (0.13%)
Calculus urinary † 1	0/788 (0.00%)	1/1550 (0.06%)
Hypertonic bladder † 1	1/788 (0.13%)	0/1550 (0.00%)
Bladder spasm † 1	0/788 (0.00%)	1/1550 (0.06%)
Cystitis interstitial † 1	0/788 (0.00%)	1/1550 (0.06%)
Renal artery stenosis † 1	0/788 (0.00%)	1/1550 (0.06%)
Ureteric stenosis † 1	0/788 (0.00%)	1/1550 (0.06%)
Reproductive system and breast disorders
Menorrhagia † 1	0/788 (0.00%)	1/1550 (0.06%)
Metrorrhagia † 1	0/788 (0.00%)	1/1550 (0.06%)
Galactorrhoea † 1	0/788 (0.00%)	1/1550 (0.06%)
Ovarian cyst † 1	0/788 (0.00%)	1/1550 (0.06%)
Prostatomegaly † 1	1/788 (0.13%)	0/1550 (0.00%)
Uterine haemorrhage † 1	0/788 (0.00%)	1/1550 (0.06%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease † 1	6/788 (0.76%)	4/1550 (0.26%)
Asthma † 1	1/788 (0.13%)	3/1550 (0.19%)
Dyspnoea † 1	0/788 (0.00%)	1/1550 (0.06%)
Epistaxis † 1	0/788 (0.00%)	1/1550 (0.06%)
Pulmonary embolism † 1	1/788 (0.13%)	6/1550 (0.39%)
Pleural effusion † 1	2/788 (0.25%)	1/1550 (0.06%)
Bronchitis chronic † 1	0/788 (0.00%)	1/1550 (0.06%)
Acute respiratory distress syndrome † 1	0/788 (0.00%)	1/1550 (0.06%)
Laryngeal oedema † 1	0/788 (0.00%)	1/1550 (0.06%)
Pneumonia aspiration † 1	1/788 (0.13%)	1/1550 (0.06%)
Pulmonary hypertension † 1	0/788 (0.00%)	1/1550 (0.06%)
Acute respiratory failure † 1	1/788 (0.13%)	0/1550 (0.00%)
Pulmonary oedema † 1	1/788 (0.13%)	0/1550 (0.00%)
Skin and subcutaneous tissue disorders
Rash † 1	0/788 (0.00%)	1/1550 (0.06%)
Dermatitis allergic † 1	0/788 (0.00%)	1/1550 (0.06%)
Angioedema † 1	0/788 (0.00%)	1/1550 (0.06%)
Hypersensitivity vasculitis † 1	0/788 (0.00%)	1/1550 (0.06%)
Vascular disorders
Hypertension † 1	2/788 (0.25%)	0/1550 (0.00%)
Hypotension † 1	1/788 (0.13%)	1/1550 (0.06%)
Deep vein thrombosis † 1	0/788 (0.00%)	2/1550 (0.13%)
Peripheral arterial occlusive disease † 1	1/788 (0.13%)	4/1550 (0.26%)
Peripheral vascular disorder † 1	1/788 (0.13%)	1/1550 (0.06%)
Thrombophlebitis † 1	1/788 (0.13%)	0/1550 (0.00%)
Aortic aneurysm † 1	1/788 (0.13%)	0/1550 (0.00%)
Iliac artery occlusion † 1	0/788 (0.00%)	2/1550 (0.13%)
Peripheral artery stenosis † 1	0/788 (0.00%)	1/1550 (0.06%)
Subclavian artery stenosis † 1	1/788 (0.13%)	1/1550 (0.06%)
Aortic aneurysm rupture † 1	0/788 (0.00%)	1/1550 (0.06%)
Aortic dissection † 1	0/788 (0.00%)	1/1550 (0.06%)
Extremity necrosis † 1	1/788 (0.13%)	1/1550 (0.06%)
Femoral artery aneurysm † 1	0/788 (0.00%)	1/1550 (0.06%)
Hypertensive crisis † 1	1/788 (0.13%)	0/1550 (0.00%)
Peripheral ischaemia † 1	2/788 (0.25%)	1/1550 (0.06%)
Hypovolaemic shock † 1	1/788 (0.13%)	0/1550 (0.00%)
Lymphocele † 1	1/788 (0.13%)	0/1550 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 17.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo Q2W	Alirocumab 150 mg Q2W
	Affected / at Risk (%)	Affected / at Risk (%)
Total	366/788 (46.45%)	707/1550 (45.61%)
Gastrointestinal disorders
Diarrhoea † 1	45/788 (5.71%)	89/1550 (5.74%)
General disorders
Injection site reaction † 1	33/788 (4.19%)	91/1550 (5.87%)
Infections and infestations
Nasopharyngitis † 1	103/788 (13.07%)	209/1550 (13.48%)
Upper respiratory tract infection † 1	68/788 (8.63%)	114/1550 (7.35%)
Urinary tract infection † 1	54/788 (6.85%)	87/1550 (5.61%)
Influenza † 1	43/788 (5.46%)	88/1550 (5.68%)
Bronchitis † 1	40/788 (5.08%)	83/1550 (5.35%)
Musculoskeletal and connective tissue disorders
Back pain † 1	52/788 (6.60%)	84/1550 (5.42%)
Myalgia † 1	23/788 (2.92%)	84/1550 (5.42%)
Arthralgia † 1	52/788 (6.60%)	80/1550 (5.16%)
Nervous system disorders
Headache † 1	44/788 (5.58%)	76/1550 (4.90%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 17.1

Limitations and Caveats

Manual reclassification was done by the Sponsor for the "other reasons" of non-completion of study as specified in the electronic case report (eCRF) form.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.

Results Point of Contact

• Name/Title: Trial Transparency Team
• Organization: Sanofi
• EMail: Contact-US@sanofi.com

Publications of Results:

Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, Stroes ES, Langslet G, Raal FJ, El Shahawy M, Koren MJ, Lepor NE, Lorenzato C, Pordy R, Chaudhari U, Kastelein JJ; ODYSSEY LONG TERM Investigators. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015 Apr 16;372(16):1489-99. doi: 10.1056/NEJMoa1501031. Epub 2015 Mar 15.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Mahmood T, Minnier J, Ito MK, Li QH, Koren A, Kam IW, Fazio S, Shapiro MD. Discordant responses of plasma low-density lipoprotein cholesterol and lipoprotein(a) to alirocumab: A pooled analysis from 10 ODYSSEY Phase 3 studies. Eur J Prev Cardiol. 2021 Jul 23;28(8):816-822. doi: 10.1177/2047487320915803. Epub 2020 Apr 10.

Leiter LA, Tinahones FJ, Karalis DG, Bujas-Bobanovic M, Letierce A, Mandel J, Samuel R, Jones PH. Alirocumab safety in people with and without diabetes mellitus: pooled data from 14 ODYSSEY trials. Diabet Med. 2018 Dec;35(12):1742-1751. doi: 10.1111/dme.13817. Epub 2018 Oct 9.

Defesche JC, Stefanutti C, Langslet G, Hopkins PN, Seiz W, Baccara-Dinet MT, Hamon SC, Banerjee P, Kastelein JJP. Efficacy of alirocumab in 1191 patients with a wide spectrum of mutations in genes causative for familial hypercholesterolemia. J Clin Lipidol. 2017 Nov - Dec;11(6):1338-1346.e7. doi: 10.1016/j.jacl.2017.08.016. Epub 2017 Sep 4. Erratum in: J Clin Lipidol. 2020 Sep - Oct;14(5):742.

Kastelein JJ, Hovingh GK, Langslet G, Baccara-Dinet MT, Gipe DA, Chaudhari U, Zhao J, Minini P, Farnier M. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 monoclonal antibody alirocumab vs placebo in patients with heterozygous familial hypercholesterolemia. J Clin Lipidol. 2017 Jan - Feb;11(1):195-203.e4. doi: 10.1016/j.jacl.2016.12.004. Epub 2016 Dec 28.

Ray KK, Ginsberg HN, Davidson MH, Pordy R, Bessac L, Minini P, Eckel RH, Cannon CP. Reductions in Atherogenic Lipids and Major Cardiovascular Events: A Pooled Analysis of 10 ODYSSEY Trials Comparing Alirocumab With Control. Circulation. 2016 Dec 13;134(24):1931-1943. Epub 2016 Oct 24.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT01507831
• Other Study ID Numbers: LTS11717; 2011-002806-59 ( EudraCT Number ); U1111-1121-3928 ( Other Identifier: UTN )
• First Submitted: January 6, 2012
• First Posted: January 11, 2012
• Results First Submitted: November 18, 2015
• Results First Posted: December 22, 2015
• Last Update Posted: December 22, 2015