Study of the Safety and Efficacy of REGN727/SAR236553 in Patients With HeFH Hypercholesterolemia

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	Hypercholesterolemia
Interventions	Drug: Alirocumab; Drug: Placebo
Enrollment	77

Participant Flow

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Recruitment Details	The study was conducted at 16 centers in the United States of America and Canada. Overall, 118 participants were screened between January 2011 and June 2011.
Pre-assignment Details	Randomization was stratified by concomitant use of ezetimibe (Yes/No). Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 1:1:1:1:1 ratio after confirmation of selection criteria. 77 participants were randomized.

Arm/Group Title	Placebo	Alirocumab 150 mg Q4W	Alirocumab 200 mg Q4W	Alirocumab 300 mg Q4W	Alirocumab 150 mg Q2W
Arm/Group Description	Placebo subcutaneous (SC) injection once every two weeks (Q2W) added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection once every 4 weeks (Q4W) added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Period Title: Overall Study
Started	15	15	16	15	16
Completed	15	15	16	14	16
Not Completed	0	0	0	1	0
Reason Not Completed
Adverse Event	0	0	0	1	0

Baseline Characteristics

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Arm/Group Title		Placebo	Alirocumab 150 mg Q4W	Alirocumab 200 mg Q4W	Alirocumab 300 mg Q4W	Alirocumab 150 mg Q2W	Total
Arm/Group Description		Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Total of all reporting groups
Overall Number of Baseline Participants		15	15	16	15	16	77
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	15 participants	15 participants	16 participants	15 participants	16 participants	77 participants
		51.9 (9.6)	51.3 (7.7)	52.9 (11.2)	54.3 (9.6)	56.3 (10.2)	53.4 (9.7)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	15 participants	15 participants	16 participants	15 participants	16 participants	77 participants
	Female	6 40.0%	6 40.0%	7 43.8%	8 53.3%	3 18.8%	30 39.0%
	Male	9 60.0%	9 60.0%	9 56.3%	7 46.7%	13 81.3%	47 61.0%
Low Density Lipoprotein Cholesterol (LDL-C) in mg/dL [1]; Mean (Standard Deviation); Unit of measure: mg/dL
	Number Analyzed	15 participants	15 participants	16 participants	15 participants	16 participants	77 participants
		150.8 (34.0)	166.7 (50.1)	169.8 (57.0)	139.6 (24.7)	147.2 (32.6)	154.9 (42.1)
		[1] Measure Description: Calculated LDL-C from Friedewald formula.

Outcome Measures

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1. Primary Outcome

Title	Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis
Description	Calculated LDL-C values were obtained using the Friedewald formula. Baseline adjusted least squares (LS) means and standard errors were estimated using an analysis of covariance (ANCOVA) model including available post-baseline data on treatment from first investigational medicinal product (IMP) injection up to 21 days after last IMP injection (on-treatment analysis). Missing Week 12 data were imputed by last observation carried forward [LOCF] method.
Time Frame	From Baseline to Week 12 (LOCF)

Outcome Measure Data

Analysis Population Description

Modified Intent-To-Treat (mITT) population included all randomized participants with one baseline and at least one post baseline on-treatment calculated LDL-C.

Arm/Group Title	Placebo	Alirocumab 150 mg Q4W	Alirocumab 200 mg Q4W	Alirocumab 300 mg Q4W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Overall Number of Participants Analyzed	15	15	16	15	16
Least Squares Mean (Standard Error); Unit of Measure: percent change
	-10.7 (5.0)	-28.9 (5.1)	-31.5 (4.9)	-42.5 (5.1)	-67.9 (4.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alirocumab 150 mg Q2W
	Comments	Each treatment group was compared to placebo using ANCOVA-derived contrasts. A hierarchical testing procedure was applied to ensure strong control of overall Type-I error rate at 0.05 level. Order was following: Alirocumab 150 mg Q2W versus placebo; Alirocumab 300 mg Q4W versus placebo; Alirocumab 200 mg Q4W versus placebo; Alirocumab 150 mg Q4W versus placebo Testing continued only when high-order test was statistically significant at 5% level.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0000
	Comments	Threshold for significance at ≤ 0.05.
	Method	ANCOVA
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alirocumab 300 mg Q4W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0000
	Comments	Threshold for significance at ≤ 0.05.
	Method	ANCOVA
	Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alirocumab 200 mg Q4W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0035
	Comments	Threshold for significance at ≤ 0.05.
	Method	ANCOVA
	Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alirocumab 150 mg Q4W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0113
	Comments	Threshold for significance at ≤ 0.05.
	Method	ANCOVA
	Comments	[Not Specified]

2. Secondary Outcome

Title	Absolute Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis
Description	Calculated LDL-C value was obtained from Friedewald formula. Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time Frame	From Baseline to Week 12 (LOCF)

Outcome Measure Data

Analysis Population Description

mITT population included all randomized participants with one baseline and at least one on-treatment calculated LDL-C.

Arm/Group Title	Placebo	Alirocumab 150 mg Q4W	Alirocumab 200 mg Q4W	Alirocumab 300 mg Q4W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Overall Number of Participants Analyzed	15	15	16	15	16
Least Squares Mean (Standard Error); Unit of Measure: mg/dL
	-19.1 (7.9)	-42.2 (8.0)	-51.3 (7.7)	-66.9 (8.0)	-102.5 (7.6)

3. Secondary Outcome

Title	Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 12 - On-treatment Analysis
Description	Calculated LDL-C value was obtained from Friedewald formula.
Time Frame	Week 12 (LOCF)

Outcome Measure Data

Analysis Population Description

mITT population included all randomized participants with one baseline and at least one on-treatment calculated LDL-C.

Arm/Group Title	Placebo	Alirocumab 150 mg Q4W	Alirocumab 200 mg Q4W	Alirocumab 300 mg Q4W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Overall Number of Participants Analyzed	15	15	16	15	16
Measure Type: Number; Unit of Measure: percentage of participants
	13.3	26.7	18.8	66.7	93.8

4. Secondary Outcome

Title	Percentage of Participants Achieving LDL-C < 70 mg/dL (1.81 mmol/L) at Week 12 - On-treatment Analysis
Description	Calculated LDL-C value was obtained from Friedewald formula.
Time Frame	Week 12 (LOCF)

Outcome Measure Data

Analysis Population Description

mITT population included all randomized participants with one baseline and at least one on-treatment calculated LDL-C.

Arm/Group Title	Placebo	Alirocumab 150 mg Q4W	Alirocumab 200 mg Q4W	Alirocumab 300 mg Q4W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Overall Number of Participants Analyzed	15	15	16	15	16
Measure Type: Number; Unit of Measure: percentage of participants
	0.0	13.3	12.5	46.7	81.3

5. Secondary Outcome

Title	Percent Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis
Description	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time Frame	From Baseline to Week 12 (LOCF)

Outcome Measure Data

Analysis Population Description

mITT population included all randomized participants with one baseline and at least one on-treatment total cholesterol value.

Arm/Group Title	Placebo	Alirocumab 150 mg Q4W	Alirocumab 200 mg Q4W	Alirocumab 300 mg Q4W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Overall Number of Participants Analyzed	15	15	16	15	16
Least Squares Mean (Standard Error); Unit of Measure: percent change
	-8.5 (3.8)	-18.1 (3.9)	-19.7 (3.7)	-25.7 (3.8)	-43.6 (3.7)

6. Secondary Outcome

Title	Absolute Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis
Description	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time Frame	From Baseline to Week 12 (LOCF)

Outcome Measure Data

Analysis Population Description

mITT population included all randomized participants with one baseline and at least one post baseline on-treatment total cholesterol value.

Arm/Group Title	Placebo	Alirocumab 150 mg Q4W	Alirocumab 200 mg Q4W	Alirocumab 300 mg Q4W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Overall Number of Participants Analyzed	15	15	16	15	16
Least Squares Mean (Standard Error); Unit of Measure: mg/dL
	-20.3 (9.4)	-40.3 (9.5)	-50.1 (9.2)	-61.7 (9.5)	-99.9 (9.1)

7. Secondary Outcome

Title	Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12 - On-treatment Analysis
Description	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint..
Time Frame	From Baseline to Week 12 (LOCF)

Outcome Measure Data

Analysis Population Description

mITT population included all randomized participants with one baseline and at least one on-treatment HDL-C value.

Arm/Group Title	Placebo	Alirocumab 150 mg Q4W	Alirocumab 200 mg Q4W	Alirocumab 300 mg Q4W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Overall Number of Participants Analyzed	15	15	16	15	16
Least Squares Mean (Standard Error); Unit of Measure: percent change
	2.2 (3.7)	7.9 (3.7)	6.5 (3.5)	1.00 (3.8)	12.3 (3.6)

8. Secondary Outcome

Title	Absolute Change From Baseline in HDL-C at Week 12 - On-treatment Analysis
Description	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time Frame	From Baseline to Week 12 (LOCF)

Outcome Measure Data

Analysis Population Description

mITT population included all randomized participants with one baseline and at least one post baseline HDL-C value.

Arm/Group Title	Placebo	Alirocumab 150 mg Q4W	Alirocumab 200 mg Q4W	Alirocumab 300 mg Q4W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Overall Number of Participants Analyzed	15	15	16	15	16
Least Squares Mean (Standard Error); Unit of Measure: mg/dL
	0.4 (1.9)	4.2 (1.9)	3.3 (1.8)	4.5 (2.0)	6.0 (1.8)

9. Secondary Outcome

Title	Percent Change From Baseline in Triglycerides at Week 12 - On-treatment Analysis
Description	Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameter, percent changes were expressed as median (interquartile range)
Time Frame	From Baseline to Week 12 (LOCF)

Outcome Measure Data

Analysis Population Description

mITT population included all randomized participants with one baseline and at least one post baseline on-treatment fasting triglycerides value.

Arm/Group Title	Placebo	Alirocumab 150 mg Q4W	Alirocumab 200 mg Q4W	Alirocumab 300 mg Q4W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Overall Number of Participants Analyzed	15	15	16	15	16
Median (Inter-Quartile Range); Unit of Measure: percent change
	-10.6; (-28.5 to 9.5)	-16.7; (-30.1 to 21.1)	-13.2; (-30.9 to 7.4)	-4.9; (-17.0 to 10.3)	-16.2; (-30.7 to 25.1)

10. Secondary Outcome

Title	Absolute Change From Baseline in Triglycerides at Week at 12 - On-treatment Analysis
Description	Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameters, percent changes were expressed as median (interquartile range)
Time Frame	From Baseline to Week 12 (LOCF)

Outcome Measure Data

Analysis Population Description

mITT population included all randomized participants with one baseline and at least one post baseline on-treatment fasting triglycerides value.

Arm/Group Title	Placebo	Alirocumab 150 mg Q4W	Alirocumab 200 mg Q4W	Alirocumab 300 mg Q4W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Overall Number of Participants Analyzed	15	15	16	15	16
Median (Inter-Quartile Range); Unit of Measure: mg/dL
	-11.0; (-89.5 to 7.5)	-20.0; (-37.0 to 13.0)	-13.5; (-35.3 to 9.5)	-3.5; (-33.0 to 6.0)	-14.8; (-64.5 to 34.0)

11. Secondary Outcome

Title	Percent Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis
Description	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time Frame	From Baseline to Week 12

Outcome Measure Data

Analysis Population Description

mITT population included all randomized participants with one baseline and at least one post baseline on-treatment non-HDL-C value.

Arm/Group Title	Placebo	Alirocumab 150 mg Q4W	Alirocumab 200 mg Q4W	Alirocumab 300 mg Q4W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Overall Number of Participants Analyzed	15	15	16	15	16
Least Squares Mean (Standard Error); Unit of Measure: percent change
	-11.3 (4.7)	-26.8 (4.8)	-27.4 (4.6)	-39.0 (4.8)	-57.9 (4.6)

12. Secondary Outcome

Title	Absolute Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis
Description	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time Frame	From Baseline to Week 12 (LOCF)

Outcome Measure Data

Analysis Population Description

mITT population included all randomized participants with one baseline and at least one post baseline on-treatment non-HDL-C value.

Arm/Group Title	Placebo	Alirocumab 150 mg Q4W	Alirocumab 200 mg Q4W	Alirocumab 300 mg Q4W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Overall Number of Participants Analyzed	15	15	16	15	16
Least Squares Mean (Standard Error); Unit of Measure: mg/dL
	-22.8 (8.8)	-46.0 (8.9)	-52.3 (8.6)	-70.6 (9.0)	-103.6 (8.5)

13. Secondary Outcome

Title	Percent Change From Baseline in Apo Lipoprotein B (Apo-B) at Week 12 - On-treatment Analysis
Description	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time Frame	From Baseline to Week 12 (LOCF)

Outcome Measure Data

Analysis Population Description

mITT population included all randomized participants with one baseline and at least one post baseline on-treatment Apo-B value.

Arm/Group Title	Placebo	Alirocumab 150 mg Q4W	Alirocumab 200 mg Q4W	Alirocumab 300 mg Q4W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Overall Number of Participants Analyzed	15	15	16	15	16
Least Squares Mean (Standard Error); Unit of Measure: percent change
	-6.4 (4.2)	-20.9 (4.2)	-20.9 (4.0)	-28.4 (4.3)	-50.2 (4.0)

14. Secondary Outcome

Title	Absolute Change From Baseline in Apo-B at Week 12 - On-treatment Analysis
Description	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time Frame	From Baseline to Week 12

Outcome Measure Data

Analysis Population Description

mITT population included all randomized participants with one baseline and at least one post baseline on-treatment Apo-B value.

Arm/Group Title	Placebo	Alirocumab 150 mg Q4W	Alirocumab 200 mg Q4W	Alirocumab 300 mg Q4W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Overall Number of Participants Analyzed	15	15	16	15	16
Least Squares Mean (Standard Error); Unit of Measure: mg/dL
	-9.3 (5.5)	-24.3 (5.5)	-28.7 (5.3)	-34.7 (5.6)	-64.4 (5.3)

15. Secondary Outcome

Title	Percent Change From Baseline in Apolipoprotein - A1 (Apo-A1) at Week 12 - On-treatment Analysis
Description	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time Frame	From Baseline to Week 12 (LOCF)

Outcome Measure Data

Analysis Population Description

mITT population included all randomized participants with one baseline and at least one post baseline on-treatment Apo-A1 value.

Arm/Group Title	Placebo	Alirocumab 150 mg Q4W	Alirocumab 200 mg Q4W	Alirocumab 300 mg Q4W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Overall Number of Participants Analyzed	15	15	16	15	16
Least Squares Mean (Standard Error); Unit of Measure: percent change
	-5.3 (3.1)	2.4 (3.1)	1.7 (2.9)	5.6 (3.1)	8.8 (2.9)

16. Secondary Outcome

Title	Absolute Change From Baseline in Apo-A1 at Week 12 - On-treatment Analysis
Description	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time Frame	From Baseline to Week 12 (LOCF)

Outcome Measure Data

Analysis Population Description

mITT population included all randomized participants with one baseline and at least one post baseline on-treatment Apo-A1 value.

Arm/Group Title	Placebo	Alirocumab 150 mg Q4W	Alirocumab 200 mg Q4W	Alirocumab 300 mg Q4W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Overall Number of Participants Analyzed	15	15	16	15	16
Least Squares Mean (Standard Error); Unit of Measure: mg/dL
	-9.7 (4.6)	3.4 (4.5)	2.8 (4.3)	7.8 (4.6)	11.0 (4.4)

17. Secondary Outcome

Title	Absolute Change in the Ratio ApoB/ApoA-1 From Baseline to Week 12 - On-treatment Analysis
Description	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time Frame	From Baseline to Week 12

Outcome Measure Data

Analysis Population Description

mITT population included all randomized participants with one baseline and at least one post baseline on-treatment Apo-B and ApoA-1 value.

Arm/Group Title	Placebo	Alirocumab 150 mg Q4W	Alirocumab 200 mg Q4W	Alirocumab 300 mg Q4W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Overall Number of Participants Analyzed	15	15	16	15	16
Least Squares Mean (Standard Error); Unit of Measure: ratio
	-0.03 (0.04)	-0.18 (0.04)	-0.20 (0.04)	-0.25 (0.04)	-0.49 (0.04)

18. Secondary Outcome

Title	Percent Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis
Description	Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameters, percent changes were expressed as median (interquartile range)
Time Frame	From Baseline to Week 12 (LOCF)

Outcome Measure Data

Analysis Population Description

mITT population included all randomized participants with one baseline and at least one post baseline on-treatment lipoprotein(a) value.

Arm/Group Title	Placebo	Alirocumab 150 mg Q4W	Alirocumab 200 mg Q4W	Alirocumab 300 mg Q4W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Overall Number of Participants Analyzed	15	15	16	15	16
Median (Inter-Quartile Range); Unit of Measure: percent change
	-3.9; (-18.4 to 0.0)	-10.1; (-22.2 to 3.8)	-7.5; (-22.5 to 0.0)	-15.3; (-25.2 to 10.6)	-23.4; (-44.6 to -6.6)

19. Secondary Outcome

Title	Absolute Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis
Description	Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameter, percent changes were expressed as median (interquartile range)
Time Frame	From Baseline to Week 12 (LOCF)

Outcome Measure Data

Analysis Population Description

mITT population included all randomized participants with one baseline and at least one post baseline on-treatment lipoprotein(a) value.

Arm/Group Title	Placebo	Alirocumab 150 mg Q4W	Alirocumab 200 mg Q4W	Alirocumab 300 mg Q4W	Alirocumab 150 mg Q2W
Arm/Group Description:	Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.	Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Overall Number of Participants Analyzed	15	15	16	15	16
Median (Inter-Quartile Range); Unit of Measure: mg/dL
	-2.0; (-7.0 to 0.0)	-1.5; (-10.0 to 1.5)	-1.8; (-5.0 to 0.0)	-8.0; (-19.0 to 5.0)	-11.5; (-26.0 to 1.8)

Adverse Events

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Top of Page Participant Flow Baseline Characteristics Outcome Measures Adverse Events Limitations and Caveats Information More Information

Time Frame	From Baseline up to Week 12
Adverse Event Reporting Description	Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first dose of study drug to the last dose of study drug + 70 days (10 weeks) are reported.
Arm/Group Title	Placebo		Alirocumab 150 mg Q4W		Alirocumab 200 mg Q4W		Alirocumab 300 mg Q4W		Alirocumab 150 mg Q2W
Arm/Group Description	Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.		Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.		Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.		Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.		Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
All-Cause Mortality
	Placebo		Alirocumab 150 mg Q4W		Alirocumab 200 mg Q4W		Alirocumab 300 mg Q4W		Alirocumab 150 mg Q2W
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--		--/--		--/--
Serious Adverse Events
	Placebo		Alirocumab 150 mg Q4W		Alirocumab 200 mg Q4W		Alirocumab 300 mg Q4W		Alirocumab 150 mg Q2W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/15 (6.67%)		0/15 (0.00%)		0/16 (0.00%)		0/15 (0.00%)		0/16 (0.00%)
Gastrointestinal disorders
Intestinal obstruction † 1	1/15 (6.67%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (14.1)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo		Alirocumab 150 mg Q4W		Alirocumab 200 mg Q4W		Alirocumab 300 mg Q4W		Alirocumab 150 mg Q2W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/15 (60.00%)		12/15 (80.00%)		13/16 (81.25%)		13/15 (86.67%)		12/16 (75.00%)
Blood and lymphatic system disorders
Anaemia † 1	1/15 (6.67%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Ear and labyrinth disorders
Cerumen impaction † 1	1/15 (6.67%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Tinnitus † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0
Eye disorders
Conjunctivitis † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1
Ocular icterus † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1
Gastrointestinal disorders
Abdominal discomfort † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0
Abdominal distension † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	1/16 (6.25%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0
Abdominal pain † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	1/16 (6.25%)	1	0/15 (0.00%)	0	1/16 (6.25%)	1
Abdominal pain upper † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Constipation † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1
Diarrhoea † 1	0/15 (0.00%)	0	3/15 (20.00%)	4	3/16 (18.75%)	3	1/15 (6.67%)	1	0/16 (0.00%)	0
Flatulence † 1	0/15 (0.00%)	0	1/15 (6.67%)	2	1/16 (6.25%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0
Gastritis erosive † 1	1/15 (6.67%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Gingivitis † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0
Gingivitis ulcerative † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0
Haematochezia † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Haemorrhoids † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1
Intestinal obstruction † 1	1/15 (6.67%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Nausea † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	2/16 (12.50%)	4
Toothache † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1
General disorders
Chest discomfort † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1
Chills † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Fatigue † 1	1/15 (6.67%)	1	2/15 (13.33%)	3	1/16 (6.25%)	1	2/15 (13.33%)	2	0/16 (0.00%)	0
Feeling hot † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0
Influenza like illness † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	1/16 (6.25%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0
Injection site discolouration † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1
Injection site dryness † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	1/15 (6.67%)	2	0/16 (0.00%)	0
Injection site erythema † 1	0/15 (0.00%)	0	2/15 (13.33%)	2	4/16 (25.00%)	6	4/15 (26.67%)	12	0/16 (0.00%)	0
Injection site exfoliation † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	2	2/15 (13.33%)	3	0/16 (0.00%)	0
Injection site haematoma † 1	1/15 (6.67%)	1	3/15 (20.00%)	4	0/16 (0.00%)	0	2/15 (13.33%)	3	1/16 (6.25%)	1
Injection site haemorrhage † 1	1/15 (6.67%)	1	0/15 (0.00%)	0	2/16 (12.50%)	2	0/15 (0.00%)	0	2/16 (12.50%)	2
Injection site oedema † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0
Injection site pain † 1	0/15 (0.00%)	0	1/15 (6.67%)	2	0/16 (0.00%)	0	1/15 (6.67%)	1	2/16 (12.50%)	3
Injection site paraesthesia † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	3
Injection site pruritus † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	3/15 (20.00%)	6	0/16 (0.00%)	0
Injection site rash † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	0/15 (0.00%)	0	2/16 (12.50%)	5
Injection site reaction † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	1/15 (6.67%)	1	0/16 (0.00%)	0
Injection site swelling † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	1/15 (6.67%)	2	0/16 (0.00%)	0
Injection site urticaria † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	1/15 (6.67%)	3	0/16 (0.00%)	0
Injection site vesicles † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0
Non-Cardiac chest pain † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1
Oedema peripheral † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Pyrexia † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Infections and infestations
Bronchitis † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0
Diverticulitis † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Fungal skin infection † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Gastroenteritis † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0
Infected bites † 1	1/15 (6.67%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Influenza † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Nasopharyngitis † 1	2/15 (13.33%)	3	0/15 (0.00%)	0	2/16 (12.50%)	2	1/15 (6.67%)	1	0/16 (0.00%)	0
Oral herpes † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Pharyngitis streptococcal † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Pneumonia † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1
Prostate infection † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Rhinitis † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Sinusitis † 1	0/15 (0.00%)	0	2/15 (13.33%)	2	0/16 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0
Upper respiratory tract infection † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	2/15 (13.33%)	2	0/16 (0.00%)	0
Urinary tract infection † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	1/15 (6.67%)	1	0/16 (0.00%)	0
Vaginal infection † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	2	0/15 (0.00%)	0	0/16 (0.00%)	0
Injury, poisoning and procedural complications
Concussion † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	0/15 (0.00%)	0	1/16 (6.25%)	1
Epicondylitis † 1	1/15 (6.67%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0
Hand fracture † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0
Laceration † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0
Limb injury † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0
Muscle injury † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Muscle strain † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Rib fracture † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1
Tendon injury † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	1/15 (6.67%)	1	0/16 (0.00%)	0
Tendon rupture † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0
Investigations
Bacterial test positive † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Blood pressure increased † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1
Blood pressure systolic decreased † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1
Cardiac murmur † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0
Thyroxine decreased † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0
Urinary sediment present † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
White blood cell count decreased † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1
Metabolism and nutrition disorders
Glucose tolerance impaired † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/15 (6.67%)	1	2/15 (13.33%)	2	0/16 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0
Arthritis † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0
Exostosis † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0
Muscle spasms † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1
Musculoskeletal pain † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0
Musculoskeletal stiffness † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1
Myalgia † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0
Pain in extremity † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0
Plantar fasciitis † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0
Rotator cuff syndrome † 1	1/15 (6.67%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Tendonitis † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0
Nervous system disorders
Dizziness † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	1/16 (6.25%)	1	0/15 (0.00%)	0	1/16 (6.25%)	1
Dizziness postural † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Headache † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	0/15 (0.00%)	0	2/16 (12.50%)	2
Migraine † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1
Migraine with aura † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Sciatica † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	1/15 (6.67%)	3	0/16 (0.00%)	0
Psychiatric disorders
Depression † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1
Disorientation † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0
Panic attack † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1
Renal and urinary disorders
Calculus urinary † 1	0/15 (0.00%)	0	1/15 (6.67%)	2	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Dysuria † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0
Haematuria † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Micturition urgency † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Reproductive system and breast disorders
Haematospermia † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Bronchial hyperreactivity † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Cough † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Nasal congestion † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1
Oropharyngeal pain † 1	0/15 (0.00%)	0	2/15 (13.33%)	3	1/16 (6.25%)	1	1/15 (6.67%)	1	0/16 (0.00%)	0
Rales † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0
Rhinitis allergic † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1
Rhinorrhoea † 1	1/15 (6.67%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Skin and subcutaneous tissue disorders
Dermatitis contact † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0
Erythema † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Petechiae † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Pruritus † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0
Rash † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	1/15 (6.67%)	1	0/16 (0.00%)	0
Rash erythematous † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0
Skin burning sensation † 1	0/15 (0.00%)	0	1/15 (6.67%)	1	0/16 (0.00%)	0	0/15 (0.00%)	0	0/16 (0.00%)	0
Vascular disorders
Flushing † 1	0/15 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1	0/15 (0.00%)	0	0/16 (0.00%)	0
Hypertension † 1	2/15 (13.33%)	2	0/15 (0.00%)	0	0/16 (0.00%)	0	0/15 (0.00%)	0	1/16 (6.25%)	1
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (14.1)

Limitations and Caveats

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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

Name/Title: Clinical Trial Management

Organization: Regeneron Pharmaceuticals, Inc

EMail: clinicaltrials@regeneron.com

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

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.

Toth PP, Hamon SC, Jones SR, Martin SS, Joshi PH, Kulkarni KR, Banerjee P, Hanotin C, Roth EM, McKenney JM. Effect of alirocumab on specific lipoprotein non-high-density lipoprotein cholesterol and subfractions as measured by the vertical auto profile method: analysis of 3 randomized trials versus placebo. Lipids Health Dis. 2016 Feb 13;15:28. doi: 10.1186/s12944-016-0197-4.

Stein EA, Gipe D, Bergeron J, Gaudet D, Weiss R, Dufour R, Wu R, Pordy R. Effect of a monoclonal antibody to PCSK9, REGN727/SAR236553, to reduce low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolaemia on stable statin dose with or without ezetimibe therapy: a phase 2 randomised controlled trial. Lancet. 2012 Jul 7;380(9836):29-36. doi: 10.1016/S0140-6736(12)60771-5. Epub 2012 May 26.

Responsible Party:	Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT01266876 History of Changes
Other Study ID Numbers:	R727-CL-1003
First Submitted:	December 23, 2010
First Posted:	December 24, 2010
Results First Submitted:	August 20, 2015
Results First Posted:	September 22, 2015
Last Update Posted:	September 22, 2015