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

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

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Hypercholesterolemia
• Interventions: Drug: Alirocumab; Drug: Placebo (for Alirocumab); Drug: Non-statin LMT; Other: Diet Alone
• Enrollment: 233

Participant Flow

Recruitment Details	The study was conducted at 43 centers in 8 countries. A total of 402 participants were screened between December-2013 and May-2014, of whom 233 were randomized for double-blind (DB) treatment period and 169 were screen failures. Out of 233 randomized for DB period, 205 participants entered the optional open-label (OL) extension period.
Pre-assignment Details	Randomization was stratified by statin intolerant status & background therapy (non-statin lipid therapy vs diet). Randomization followed a 1:2:1 ratio for placebo, Alirocumab 75 mg and Alirocumab 150 mg instead of 1:1:2 as initially planned due to systematic error in treatment allocation algorithm discovered after all participants were randomized.

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator)	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description	Period 1: Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. Period 2: Alirocumab 150 mg SC injection every 4 weeks (Q4W) from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and low-density lipoprotein cholesterol (LDL-C) values. Subsequent down titration to 150 mg Q4W was allowed.	Period 1: Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline. Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed.	Period 1: Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline. Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed.
Period Title: Period 1: 24-Week Double-blind Treatment
Started	58	116	59
Treated	58	115	58
Completed	54	107	50
Not Completed	4	9	9
Reason Not Completed
Adverse Event	2	2	5
Poor compliance to protocol	0	2	1
Physician Decision	0	1	0
Consent withdrawn by participant	1	0	1
Randomized but not treated	0	1	1
Other than specified above	1	3	1
Period Title: Extension Open Label Treatment
Started	51 [1]	106 [1]	48 [1]
Completed	46	89	43
Not Completed	5	17	5
Reason Not Completed
Adverse Event	1	7	3
Poor compliance to protocol	1	1	0
Participant moved	1	2	0
Other than specified above	2	7	2
[1] The open-label extension period was optional for participants who completed the double-blind period.

Baseline Characteristics

Arm/Group Title		Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator)	Alirocumab 150 mg Q4W/Up to 150 mg Q2W	Total
Arm/Group Description		Period 1: Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. Period 2: Alirocumab 150 mg SC injection every 4 weeks (Q4W) from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and low-density lipoprotein cholesterol (LDL-C) values. Subsequent down titration to 150 mg Q4W was allowed.	Period 1: Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline. Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed.	Period 1: Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline. Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed.	Total of all reporting groups
Overall Number of Baseline Participants		58	116	59	233
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	58 participants	116 participants	59 participants	233 participants
		63.1 (10.7)	62.5 (9.9)	64.2 (10.0)	63.1 (10.1)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	58 participants	116 participants	59 participants	233 participants
	Female	27 46.6%	47 40.5%	29 49.2%	103 44.2%
	Male	31 53.4%	69 59.5%	30 50.8%	130 55.8%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	58 participants	116 participants	59 participants	233 participants
	Hispanic or Latino	1 1.7%	7 6.0%	4 6.8%	12 5.2%
	Not Hispanic or Latino	57 98.3%	109 94.0%	54 91.5%	220 94.4%
	Unknown or Not Reported	0 0.0%	0 0.0%	1 1.7%	1 0.4%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	58 participants	116 participants	59 participants	233 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	1 1.7%	4 3.4%	3 5.1%	8 3.4%
	Native Hawaiian or Other Pacific Islander	0 0.0%	1 0.9%	0 0.0%	1 0.4%
	Black or African American	1 1.7%	3 2.6%	1 1.7%	5 2.1%
	White	56 96.6%	108 93.1%	55 93.2%	219 94.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Calculated LDL-C in mg/dL [1]; Mean (Standard Deviation); Unit of measure: mg/dL
	Number Analyzed	58 participants	116 participants	59 participants	233 participants
		158.5 (47.3)	154.5 (44.6)	163.9 (69.1)	157.9 (52.4)
		[1] Measure Description: Calculated LDL-C from Friedewald formula (LDL-C = Total cholesterol [Total-C] - High-Density Lipoprotein Cholesterol [HDL-C] - [Triglyceride/5]).
Calculated LDL-C in mmol/L; Mean (Standard Deviation); Unit of measure: mmol/L
	Number Analyzed	58 participants	116 participants	59 participants	233 participants
		4.106 (1.226)	4.002 (1.154)	4.245 (1.789)	4.089 (1.356)

Outcome Measures

1. Primary 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 24 regardless of status on- or off-treatment were used in the model (ITT analysis).
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator)	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	57	115	58
Least Squares Mean (Standard Error); Unit of Measure: percent change
	4.7 (2.3)	-53.5 (1.6)	-51.7 (2.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q4W/Up to 150 mg Q2W
	Comments	Alirocumab 150 mg Q4W/up to 150 mg Q2W was compared to placebo group using an appropriate contrast statement.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least square (LS) mean difference
	Estimated Value	-56.4
	Confidence Interval	(2-Sided) 95%; -62.9 to -49.9
	Estimation Comments	Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	56	115	57
Least Squares Mean (Standard Error); Unit of Measure: percent change
	5.1 (2.1)	-55.3 (1.5)	-54.6 (2.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q4W/Up to 150 mg Q2W
	Comments	A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 0.05 level.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-59.7
	Confidence Interval	(2-Sided) 95%; -65.6 to -53.8
	Estimation Comments	Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo

3. Secondary Outcome

Title	Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	57	115	58
Least Squares Mean (Standard Error); Unit of Measure: percent change
	3.2 (2.5)	-50.8 (1.7)	-41.7 (2.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q4W/Up to 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-44.9
	Confidence Interval	(2-Sided) 95%; -51.8 to -38.1
	Estimation Comments	Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo

4. Secondary Outcome

Title	Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
Description	Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	56	115	57
Least Squares Mean (Standard Error); Unit of Measure: percent change
	3.6 (2.3)	-51.5 (1.6)	-44.8 (2.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q4W/Up to 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-48.4
	Confidence Interval	(2-Sided) 95%; -54.8 to -41.9
	Estimation Comments	Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo

5. Secondary Outcome

Title	Percent Change From Baseline in Calculated LDL-C to Averaged Weeks 9 to 12 – ITT- Analysis
Description	Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment and assigning a weight of 0.25 for Week 9, 10, 11 and 12 time points.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	57	115	58
Least Squares Mean (Standard Error); Unit of Measure: percent change
	3.2 (2.0)	-53.6 (1.4)	-52.3 (2.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q4W/Up to 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-55.5
	Confidence Interval	(2-Sided) 95%; -61.1 to -49.8
	Estimation Comments	Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo

6. Secondary Outcome

Title	Percent Change From Baseline in Calculated LDL-C at Averaged Week 9 to 12 - On-Treatment Analysis
Description	Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection) and assigning a weight of 0.25 for Week 9, 10, 11 and 12 time points.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	56	115	57
Least Squares Mean (Standard Error); Unit of Measure: percent change
	3.6 (1.9)	-54.1 (1.3)	-55.0 (1.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q4W/Up to 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-58.6
	Confidence Interval	(2-Sided) 95%; -63.8 to -53.4
	Estimation Comments	Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants of the ITT population with available data at specified time-points.

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	56	112	58
Least Squares Mean (Standard Error); Unit of Measure: percent change
	7.5 (2.1)	-39.7 (1.5)	-38.9 (2.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q4W/Up to 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-46.4
	Confidence Interval	(2-Sided) 95%; -52.4 to -40.4
	Estimation Comments	Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

mITT population. Number of participants analyzed = participants of the mITT population with available data at specified time-points.

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	54	112	54
Least Squares Mean (Standard Error); Unit of Measure: percent change
	7.7 (2.0)	-41.2 (1.4)	-40.9 (2.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q4W/Up to 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-48.6
	Confidence Interval	(2-Sided) 95%; -54.3 to -42.8
	Estimation Comments	Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	57	115	58
Least Squares Mean (Standard Error); Unit of Measure: percent change
	4.8 (2.1)	-45.3 (1.5)	-44.2 (2.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q4W/Up to 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-49.0
	Confidence Interval	(2-Sided) 95%; -54.9 to -43.2
	Estimation Comments	Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	56	115	57
Least Squares Mean (Standard Error); Unit of Measure: percent change
	5.0 (1.9)	-46.9 (1.3)	-46.7 (1.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q4W/Up to 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-51.7
	Confidence Interval	(2-Sided) 95%; -57.1 to -46.4
	Estimation Comments	Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	57	115	58
Least Squares Mean (Standard Error); Unit of Measure: percent change
	3.0 (1.6)	-34.0 (1.1)	-32.3 (1.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q4W/Up to 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-35.3
	Confidence Interval	(2-Sided) 95%; -39.8 to -30.8
	Estimation Comments	Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo

12. Secondary Outcome

Title	Percent Change From Baseline in Apo B at Week 12 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants of the ITT population with available data at specified time-points.

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	56	112	58
Least Squares Mean (Standard Error); Unit of Measure: percent change
	7.0 (2.2)	-38.4 (1.6)	-31.3 (2.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q4W/Up to 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-38.2
	Confidence Interval	(2-Sided) 95%; -44.3 to -32.1
	Estimation Comments	Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo

13. Secondary Outcome

Title	Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	57	115	58
Least Squares Mean (Standard Error); Unit of Measure: percent change
	3.0 (2.2)	-43.4 (1.5)	-34.9 (2.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q4W/Up to 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-37.9
	Confidence Interval	(2-Sided) 95%; -43.9 to -31.8
	Estimation Comments	Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo

14. Secondary Outcome

Title	Percent Change From Baseline in Total-C at Week 12 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	57	115	58
Least Squares Mean (Standard Error); Unit of Measure: percent change
	1.8 (1.6)	-32.6 (1.2)	-24.5 (1.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q4W/Up to 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-26.3
	Confidence Interval	(2-Sided) 95%; -30.9 to -21.7
	Estimation Comments	Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo

15. Secondary Outcome

Title	Percentage of Very High Cardiovascular (CV) Risk Participants Achieving Calculated LDL-C <70 mg/dL (<1.81 mmol/L) or Moderate or High CV Risk Participants Achieving Calculated LDL-C <100 mg/dL (<2.59 mmol/L) at Week 24 - ITT Analysis
Description	Moderate CV risk: 10-year fatal cardiovascular disease (CVD) risk Systemic Coronary Risk Evaluation (SCORE) ≥1 and <5%. High CV risk: 10-year fatal CVD risk SCORE ≥5% or moderate chronic kidney disease or type 1 or type 2 diabetes mellitus without target organ damage or familial hypercholesterolemia. Very high CV risk: history of documented coronary heart disease, ischemic stroke, peripheral artery disease, transient ischemic attack, abdominal aortic aneurysm, or carotid artery occlusion >50% without symptoms; carotid endarterectomy or carotid artery stent procedure; renal artery stenosis, or renal artery stent procedure; or type 1 or type 2 diabetes mellitus with target organ damage. Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	57	115	58
Measure Type: Number; Unit of Measure: percentage of participants
	1.8	70.3	63.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q4W/Up to 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Regression, Logistic
	Comments	Multiple imputation approach followed by logistic regression model.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	279.8
	Confidence Interval	(2-Sided) 95%; 29.1 to 2690.1
	Estimation Comments	Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo

16. Secondary Outcome

Title	Percentage of Very High CV Risk Participants Achieving Calculated LDL-C< 70 mg/dL (<1.81 mmol/L) or Moderate or High CV Risk Participants Achieving Calculated LDL-C< 100 mg/dL (<2.59 mmol/L) at Week 24 – On-treatment Analysis
Description	Adjusted percentages at Week 24 from multiple imputation approach including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	56	115	57
Measure Type: Number; Unit of Measure: percentage of participants
	1.8	72.7	67.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q4W/Up to 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Regression, Logistic
	Comments	Multiple imputation approach followed by logistic regression model.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	354.7
	Confidence Interval	(2-Sided) 95%; 36.2 to 3479.5
	Estimation Comments	Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo

17. Secondary Outcome

Title	Percentage of Participants Achieving Calculated LDL-C< 70 mg/dL (<1.81 mmol/L) at Week 24 - ITT Analysis
Description	Adjusted percentages at Week 24 from last observation carried forward (LOCF) approach including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	57	115	58
Measure Type: Number; Unit of Measure: percentage of participants
	0.0	60.0	50.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q4W/Up to 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Regression, Logistic
	Comments	LOCF approach followed by logistic regression model.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	126.0
	Confidence Interval	(2-Sided) 95%; 20.0 to 9999
	Estimation Comments	Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo (Confidence interval should be read as 20.0 to >9999)

18. Secondary Outcome

Title	Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (<1.81 mmol/L) at Week 24 – On-treatment Analysis
Description	Adjusted percentages at Week 24 from LOCF approach including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	56	115	57
Measure Type: Number; Unit of Measure: percentage of participants
	0.0	61.7	50.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q4W/Up to 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Regression, Logistic
	Comments	LOCF approach followed by logistic regression model.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	141.5
	Confidence Interval	(2-Sided) 95%; 22.2 to 9999
	Estimation Comments	Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo (Confidence interval should be read as 20.0 to >9999)

19. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	57	115	58
Mean (Standard Error); Unit of Measure: percent change
	4.1 (3.7)	-21.8 (2.6)	-15.5 (3.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q4W/Up to 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0002
	Comments	Threshold for significance at 0.05 level.
	Method	Regression, Robust
	Comments	Multiple imputation approach followed by robust regression model.
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-19.6
	Confidence Interval	(2-Sided) 95%; -29.8 to -9.4
	Estimation Comments	Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo

20. Secondary Outcome

Title	Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis
Description	Adjusted means and standard errors at Week 12 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	57	115	58
Mean (Standard Error); Unit of Measure: percent change
	2.2 (3.4)	-16.5 (2.4)	-5.7 (3.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 150 mg Q4W/Up to 150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0892
	Comments	Threshold for significance at 0.05 level.
	Method	Regression, Robust
	Comments	Multiple imputation approach followed by robust regression model.
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-7.9
	Confidence Interval	(2-Sided) 95%; -17.1 to 1.2
	Estimation Comments	Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo

21. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	57	115	58
Least Squares Mean (Standard Error); Unit of Measure: percent change
	-2.4 (1.9)	7.4 (1.4)	7.7 (2.0)

22. Secondary Outcome

Title	Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	57	115	58
Least Squares Mean (Standard Error); Unit of Measure: percent change
	-0.8 (1.9)	6.8 (1.3)	8.6 (1.9)

23. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	57	115	58
Mean (Standard Error); Unit of Measure: percent change
	1.1 (3.8)	-10.6 (2.7)	-9.2 (3.9)

24. Secondary Outcome

Title	Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis
Description	Adjusted means and standard errors at Week 12 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	57	115	58
Mean (Standard Error); Unit of Measure: percent change
	2.1 (3.9)	-11.3 (2.7)	-3.0 (3.8)

25. Secondary Outcome

Title	Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants of the ITT population with available data at specified time-points.

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	56	112	58
Least Squares Mean (Standard Error); Unit of Measure: percent change
	3.4 (1.5)	8.2 (1.1)	10.0 (1.5)

26. Secondary Outcome

Title	Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants of the ITT population with available data at specified time-points.

Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Alirocumab 150 mg Q4W/Up to 150 mg Q2W
Arm/Group Description:	Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.	Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.
Overall Number of Participants Analyzed	56	112	58
Least Squares Mean (Standard Error); Unit of Measure: percent change
	2.6 (1.5)	5.9 (1.1)	7.6 (1.5)

27. Other Pre-specified Outcome

Title	Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase
Description	Mean percent changes (and standard deviations) observed during the open-label extension period are provided.
Time Frame	Baseline, Week 32, 36, 48, 72, 96, 120, 144 and Week 168

Outcome Measure Data

Analysis Population Description

Open-label extension population included all participants who received at least one dose or part of dose of Alirocumab during the open label extension period. Here, “number analyzed” signifies the number of participants evaluable for each specified time-point.

Arm/Group Title		Alirocumab 150 mg Q4W (After Placebo Q2W)	Alirocumab 150 mg QW4 (After Alirocumab 75 Q2W/Up 150 Q2W)	Alirocumab 150 mg Q4W (After Alirocumab 150 Q4W/Up 150 Q2W)
Arm/Group Description:		Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first, in participants who received placebo (for Alirocumab) Q2W for 24 weeks during the double-blind period. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and low-density lipoprotein cholesterol (LDL-C) values. Subsequent down titration to 150 mg Q4W was allowed.	Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first, in participants who received Alirocumab 75 mg Q2W/Up to 150 mg Q2W for 24 weeks during the double-blind period. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and low-density lipoprotein cholesterol (LDL-C) values. Subsequent down titration to 150 mg Q4W was allowed.	Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first, in participants who received 150 mg Q4W/Up to 150 mg Q2W for 24 weeks during the double-blind period. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and low-density lipoprotein cholesterol (LDL-C) values. Subsequent down titration to 150 mg Q4W was allowed.
Overall Number of Participants Analyzed		51	106	48
Mean (Standard Deviation); Unit of Measure: percent change
Week 32	Number Analyzed	48 participants	98 participants	45 participants
		-37.3 (18.8)	-41.1 (21.2)	-46.9 (13.3)
Week 36	Number Analyzed	48 participants	96 participants	46 participants
		-36.1 (22.0)	-39.2 (21.2)	-43.1 (13.7)
Week 48	Number Analyzed	47 participants	91 participants	44 participants
		-46.5 (24.2)	-49.2 (18.7)	-48.7 (21.7)
Week 72	Number Analyzed	50 participants	94 participants	47 participants
		-50.8 (20.6)	-53.7 (19.5)	-52.3 (21.3)
Week 96	Number Analyzed	48 participants	90 participants	44 participants
		-49.8 (20.4)	-52.8 (19.6)	-46.8 (22.0)
Week 120	Number Analyzed	46 participants	81 participants	37 participants
		-50.6 (20.9)	-53.7 (18.7)	-51.8 (24.1)
Week 144	Number Analyzed	38 participants	72 participants	29 participants
		-52.7 (17.6)	-48.7 (23.7)	-49.4 (20.9)
Week 168	Number Analyzed	4 participants	13 participants	4 participants
		-47.8 (24.2)	-66.2 (17.1)	-60.0 (4.6)

Adverse Events

Time Frame	All Adverse Events (AE) were collected from signature of informed consent form up to study completion (up to 176 weeks) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description	Reported AEs/deaths are treatment-emergent ie; AEs that developed/worsened and deaths that occurred ‘on treatment’; from 1st dose up to last dose (active/placebo depending on Q2W/Q4W dosing) in DB period+70 days, truncated at the day before 1st dose in OL period for participants entering in OL period; from 1st dose up to last dose in OL period+70 days.
Arm/Group Title	Placebo Q2W	Alirocumab 75 mg Q2W/Up150 mg Q2W	Alirocumab 150 mg Q4W/Up150 mg Q2W	Alirocumab 150 mg Q4W (After Placebo Q2W)	Alirocumab 150 mg Q4W (After Alirocumab 75 Q2W/Up150 Q2W)	Alirocumab 150 mg Q4W (After Alirocumab 150 Q4W/Up150 Q2W)
Arm/Group Description	Participants exposed to placebo SC injection Q2W added to stable non-statin LMT or diet alone (mean exposure of 23 weeks).	Participants exposed to alirocumab 75 mg Q2W/up to 150 mg Q2W SC injection added to stable non-statin LMT or diet alone (mean exposure of 23 weeks).	Participants exposed to alirocumab 150 mg Q4W/up to 150 mg Q2W SC injection added to stable non-statin LMT or diet alone (mean exposure of 22 weeks).	Participants exposed to alirocumab 150 mg Q4W SC injection added to stable non-statin LMT or diet alone (mean exposure of 128 weeks) after having received Placebo Q2W for 24 weeks.	Participants exposed to alirocumab 150 mg Q4W SC injection added to stable non-statin LMT or diet alone (mean exposure of 117 weeks) after having received Alirocumab 75 mg Q2W/Up to 150 mg Q2W for 24 weeks.	Participants exposed to alirocumab 150 mg Q4W SC injection added to stable non-statin LMT or diet alone (mean exposure of 119 weeks) after having received Alirocumab 150 mg Q4W/Up to 150 mg Q2W for 24 weeks.
All-Cause Mortality
	Placebo Q2W	Alirocumab 75 mg Q2W/Up150 mg Q2W	Alirocumab 150 mg Q4W/Up150 mg Q2W	Alirocumab 150 mg Q4W (After Placebo Q2W)	Alirocumab 150 mg Q4W (After Alirocumab 75 Q2W/Up150 Q2W)	Alirocumab 150 mg Q4W (After Alirocumab 150 Q4W/Up150 Q2W)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	2/106 (1.89%)	1/48 (2.08%)
Serious Adverse Events
	Placebo Q2W	Alirocumab 75 mg Q2W/Up150 mg Q2W	Alirocumab 150 mg Q4W/Up150 mg Q2W	Alirocumab 150 mg Q4W (After Placebo Q2W)	Alirocumab 150 mg Q4W (After Alirocumab 75 Q2W/Up150 Q2W)	Alirocumab 150 mg Q4W (After Alirocumab 150 Q4W/Up150 Q2W)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	4/58 (6.90%)	7/115 (6.09%)	7/58 (12.07%)	15/51 (29.41%)	28/106 (26.42%)	14/48 (29.17%)
Blood and lymphatic system disorders
Anaemia † 1	1/58 (1.72%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	0/106 (0.00%)	0/48 (0.00%)
Haemorrhagic anaemia † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	1/51 (1.96%)	1/106 (0.94%)	0/48 (0.00%)
Cardiac disorders
Acute coronary syndrome † 1	0/58 (0.00%)	1/115 (0.87%)	0/58 (0.00%)	0/51 (0.00%)	0/106 (0.00%)	0/48 (0.00%)
Acute myocardial infarction † 1	0/58 (0.00%)	0/115 (0.00%)	1/58 (1.72%)	0/51 (0.00%)	3/106 (2.83%)	0/48 (0.00%)
Angina pectoris † 1	0/58 (0.00%)	1/115 (0.87%)	0/58 (0.00%)	1/51 (1.96%)	0/106 (0.00%)	0/48 (0.00%)
Angina unstable † 1	0/58 (0.00%)	0/115 (0.00%)	1/58 (1.72%)	0/51 (0.00%)	0/106 (0.00%)	0/48 (0.00%)
Aortic valve stenosis † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Atrial fibrillation † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	1/51 (1.96%)	0/106 (0.00%)	1/48 (2.08%)
Cardiac failure congestive † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	1/51 (1.96%)	2/106 (1.89%)	0/48 (0.00%)
Cardio-respiratory arrest † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	0/106 (0.00%)	1/48 (2.08%)
Cardiomyopathy † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	1/51 (1.96%)	0/106 (0.00%)	0/48 (0.00%)
Coronary artery disease † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	2/106 (1.89%)	1/48 (2.08%)
Mitral valve incompetence † 1	1/58 (1.72%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	0/106 (0.00%)	0/48 (0.00%)
Myocardial infarction † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Ear and labyrinth disorders
Vertigo † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Endocrine disorders
Basedow's disease † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Eye disorders
Retinal detachment † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Gastrointestinal disorders
Abdominal pain † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Abdominal pain upper † 1	0/58 (0.00%)	1/115 (0.87%)	0/58 (0.00%)	0/51 (0.00%)	0/106 (0.00%)	0/48 (0.00%)
Abdominal wall haematoma † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Constipation † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	1/51 (1.96%)	0/106 (0.00%)	0/48 (0.00%)
Faecaloma † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	0/106 (0.00%)	1/48 (2.08%)
Gastrointestinal haemorrhage † 1	1/58 (1.72%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Retroperitoneal haematoma † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Small intestinal obstruction † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	1/48 (2.08%)
Volvulus † 1	0/58 (0.00%)	0/115 (0.00%)	1/58 (1.72%)	0/51 (0.00%)	0/106 (0.00%)	0/48 (0.00%)
General disorders
Chest pain † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Non-cardiac chest pain † 1	0/58 (0.00%)	1/115 (0.87%)	0/58 (0.00%)	0/51 (0.00%)	2/106 (1.89%)	0/48 (0.00%)
Hepatobiliary disorders
Biliary colic † 1	0/58 (0.00%)	1/115 (0.87%)	0/58 (0.00%)	0/51 (0.00%)	0/106 (0.00%)	0/48 (0.00%)
Cholelithiasis † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Infections and infestations
Appendicitis † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	1/51 (1.96%)	0/106 (0.00%)	0/48 (0.00%)
Arthritis bacterial † 1	0/58 (0.00%)	1/115 (0.87%)	0/58 (0.00%)	0/51 (0.00%)	0/106 (0.00%)	0/48 (0.00%)
Cellulitis † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	0/106 (0.00%)	1/48 (2.08%)
Device related infection † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Hepatitis E † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	1/51 (1.96%)	0/106 (0.00%)	0/48 (0.00%)
Pneumonia † 1	0/58 (0.00%)	1/115 (0.87%)	0/58 (0.00%)	1/51 (1.96%)	1/106 (0.94%)	2/48 (4.17%)
Urinary tract infection † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	1/51 (1.96%)	0/106 (0.00%)	0/48 (0.00%)
Injury, poisoning and procedural complications
Craniocerebral injury † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	1/51 (1.96%)	0/106 (0.00%)	0/48 (0.00%)
Fall † 1	1/58 (1.72%)	0/115 (0.00%)	0/58 (0.00%)	2/51 (3.92%)	1/106 (0.94%)	0/48 (0.00%)
Femur fracture † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Humerus fracture † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	1/51 (1.96%)	0/106 (0.00%)	0/48 (0.00%)
Intentional overdose † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Jaw fracture † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	0/106 (0.00%)	1/48 (2.08%)
Multiple fractures † 1	1/58 (1.72%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	0/106 (0.00%)	0/48 (0.00%)
Post procedural haematoma † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Radius fracture † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	1/51 (1.96%)	0/106 (0.00%)	0/48 (0.00%)
Rib fracture † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	1/51 (1.96%)	0/106 (0.00%)	0/48 (0.00%)
Road traffic accident † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	1/51 (1.96%)	0/106 (0.00%)	0/48 (0.00%)
Spinal fracture † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	1/51 (1.96%)	0/106 (0.00%)	0/48 (0.00%)
Subdural haematoma † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	1/51 (1.96%)	1/106 (0.94%)	0/48 (0.00%)
Traumatic haemothorax † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	1/51 (1.96%)	0/106 (0.00%)	0/48 (0.00%)
Traumatic renal injury † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	1/51 (1.96%)	0/106 (0.00%)	0/48 (0.00%)
Vascular pseudoaneurysm † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Musculoskeletal and connective tissue disorders
Arthritis † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	0/106 (0.00%)	1/48 (2.08%)
Lumbar spinal stenosis † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	0/106 (0.00%)	1/48 (2.08%)
Musculoskeletal chest pain † 1	1/58 (1.72%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	0/106 (0.00%)	1/48 (2.08%)
Myalgia † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	0/106 (0.00%)	1/48 (2.08%)
Osteoarthritis † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	1/48 (2.08%)
Rhabdomyolysis † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	0/106 (0.00%)	1/48 (2.08%)
Rheumatoid arthritis † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	1/51 (1.96%)	0/106 (0.00%)	0/48 (0.00%)
Spinal osteoarthritis † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	1/51 (1.96%)	0/106 (0.00%)	0/48 (0.00%)
Basal cell carcinoma † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	1/51 (1.96%)	2/106 (1.89%)	1/48 (2.08%)
Benign fallopian tube neoplasm † 1	0/58 (0.00%)	1/115 (0.87%)	0/58 (0.00%)	0/51 (0.00%)	0/106 (0.00%)	0/48 (0.00%)
Bladder transitional cell carcinoma † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Breast cancer † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	0/106 (0.00%)	1/48 (2.08%)
Meningioma † 1	0/58 (0.00%)	0/115 (0.00%)	1/58 (1.72%)	0/51 (0.00%)	0/106 (0.00%)	0/48 (0.00%)
Oesophageal squamous cell carcinoma † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	1/51 (1.96%)	0/106 (0.00%)	0/48 (0.00%)
Prostate cancer † 1	1/58 (1.72%)	1/115 (0.87%)	0/58 (0.00%)	1/51 (1.96%)	2/106 (1.89%)	0/48 (0.00%)
Skin cancer † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Uterine leiomyoma † 1	0/58 (0.00%)	1/115 (0.87%)	0/58 (0.00%)	0/51 (0.00%)	0/106 (0.00%)	0/48 (0.00%)
Nervous system disorders
Arachnoiditis † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Cerebellar infarction † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	0/106 (0.00%)	1/48 (2.08%)
Cerebrovascular accident † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Essential tremor † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	1/51 (1.96%)	0/106 (0.00%)	0/48 (0.00%)
Hypoxic-ischaemic encephalopathy † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	0/106 (0.00%)	1/48 (2.08%)
Multiple sclerosis relapse † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Presyncope † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	2/106 (1.89%)	0/48 (0.00%)
Syncope † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	3/106 (2.83%)	2/48 (4.17%)
Transient ischaemic attack † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Psychiatric disorders
Depression † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Mental disorder † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	0/106 (0.00%)	1/48 (2.08%)
Suicide attempt † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Renal and urinary disorders
Acute kidney injury † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	1/51 (1.96%)	0/106 (0.00%)	0/48 (0.00%)
Nephrolithiasis † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	1/51 (1.96%)	0/106 (0.00%)	0/48 (0.00%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease † 1	0/58 (0.00%)	0/115 (0.00%)	1/58 (1.72%)	0/51 (0.00%)	0/106 (0.00%)	1/48 (2.08%)
Epistaxis † 1	0/58 (0.00%)	1/115 (0.87%)	0/58 (0.00%)	0/51 (0.00%)	0/106 (0.00%)	0/48 (0.00%)
Pulmonary embolism † 1	0/58 (0.00%)	0/115 (0.00%)	1/58 (1.72%)	0/51 (0.00%)	0/106 (0.00%)	0/48 (0.00%)
Vascular disorders
Haematoma † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Hypertensive crisis † 1	0/58 (0.00%)	1/115 (0.87%)	0/58 (0.00%)	0/51 (0.00%)	0/106 (0.00%)	0/48 (0.00%)
Hypotension † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	2/106 (1.89%)	0/48 (0.00%)
Hypovolaemic shock † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
Peripheral artery occlusion † 1	0/58 (0.00%)	0/115 (0.00%)	1/58 (1.72%)	0/51 (0.00%)	0/106 (0.00%)	0/48 (0.00%)
Peripheral artery stenosis † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	0/106 (0.00%)	1/48 (2.08%)
Peripheral ischaemia † 1	0/58 (0.00%)	0/115 (0.00%)	0/58 (0.00%)	0/51 (0.00%)	1/106 (0.94%)	0/48 (0.00%)
1 Term from vocabulary, MedDRA 20.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo Q2W	Alirocumab 75 mg Q2W/Up150 mg Q2W	Alirocumab 150 mg Q4W/Up150 mg Q2W	Alirocumab 150 mg Q4W (After Placebo Q2W)	Alirocumab 150 mg Q4W (After Alirocumab 75 Q2W/Up150 Q2W)	Alirocumab 150 mg Q4W (After Alirocumab 150 Q4W/Up150 Q2W)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	28/58 (48.28%)	61/115 (53.04%)	29/58 (50.00%)	42/51 (82.35%)	71/106 (66.98%)	31/48 (64.58%)
Gastrointestinal disorders
Diarrhoea † 1	2/58 (3.45%)	5/115 (4.35%)	1/58 (1.72%)	3/51 (5.88%)	11/106 (10.38%)	2/48 (4.17%)
Nausea † 1	2/58 (3.45%)	6/115 (5.22%)	3/58 (5.17%)	1/51 (1.96%)	3/106 (2.83%)	3/48 (6.25%)
General disorders
Fatigue † 1	0/58 (0.00%)	5/115 (4.35%)	4/58 (6.90%)	3/51 (5.88%)	7/106 (6.60%)	3/48 (6.25%)
Injection site reaction † 1	0/58 (0.00%)	4/115 (3.48%)	8/58 (13.79%)	1/51 (1.96%)	7/106 (6.60%)	7/48 (14.58%)
Non-cardiac chest pain † 1	3/58 (5.17%)	3/115 (2.61%)	0/58 (0.00%)	6/51 (11.76%)	5/106 (4.72%)	1/48 (2.08%)
Oedema peripheral † 1	4/58 (6.90%)	3/115 (2.61%)	0/58 (0.00%)	4/51 (7.84%)	5/106 (4.72%)	5/48 (10.42%)
Infections and infestations
Bronchitis † 1	0/58 (0.00%)	1/115 (0.87%)	1/58 (1.72%)	3/51 (5.88%)	4/106 (3.77%)	5/48 (10.42%)
Influenza † 1	0/58 (0.00%)	3/115 (2.61%)	1/58 (1.72%)	3/51 (5.88%)	9/106 (8.49%)	4/48 (8.33%)
Pharyngitis † 1	0/58 (0.00%)	1/115 (0.87%)	0/58 (0.00%)	3/51 (5.88%)	1/106 (0.94%)	0/48 (0.00%)
Sinusitis † 1	1/58 (1.72%)	1/115 (0.87%)	0/58 (0.00%)	3/51 (5.88%)	3/106 (2.83%)	1/48 (2.08%)
Upper respiratory tract infection † 1	4/58 (6.90%)	4/115 (3.48%)	3/58 (5.17%)	7/51 (13.73%)	8/106 (7.55%)	4/48 (8.33%)
Urinary tract infection † 1	1/58 (1.72%)	4/115 (3.48%)	4/58 (6.90%)	4/51 (7.84%)	7/106 (6.60%)	5/48 (10.42%)
Viral upper respiratory tract infection † 1	3/58 (5.17%)	10/115 (8.70%)	5/58 (8.62%)	5/51 (9.80%)	16/106 (15.09%)	9/48 (18.75%)
Injury, poisoning and procedural complications
Fall † 1	1/58 (1.72%)	6/115 (5.22%)	0/58 (0.00%)	6/51 (11.76%)	14/106 (13.21%)	2/48 (4.17%)
Laceration † 1	0/58 (0.00%)	0/115 (0.00%)	1/58 (1.72%)	3/51 (5.88%)	3/106 (2.83%)	0/48 (0.00%)
Metabolism and nutrition disorders
Gout † 1	0/58 (0.00%)	0/115 (0.00%)	1/58 (1.72%)	5/51 (9.80%)	5/106 (4.72%)	1/48 (2.08%)
Hyperkalaemia † 1	1/58 (1.72%)	0/115 (0.00%)	0/58 (0.00%)	1/51 (1.96%)	1/106 (0.94%)	3/48 (6.25%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	4/58 (6.90%)	8/115 (6.96%)	7/58 (12.07%)	8/51 (15.69%)	7/106 (6.60%)	3/48 (6.25%)
Back pain † 1	0/58 (0.00%)	5/115 (4.35%)	2/58 (3.45%)	4/51 (7.84%)	10/106 (9.43%)	7/48 (14.58%)
Muscle spasms † 1	0/58 (0.00%)	9/115 (7.83%)	3/58 (5.17%)	4/51 (7.84%)	4/106 (3.77%)	1/48 (2.08%)
Musculoskeletal pain † 1	1/58 (1.72%)	3/115 (2.61%)	0/58 (0.00%)	1/51 (1.96%)	6/106 (5.66%)	2/48 (4.17%)
Myalgia † 1	3/58 (5.17%)	7/115 (6.09%)	3/58 (5.17%)	7/51 (13.73%)	6/106 (5.66%)	1/48 (2.08%)
Neck pain † 1	0/58 (0.00%)	2/115 (1.74%)	0/58 (0.00%)	3/51 (5.88%)	0/106 (0.00%)	0/48 (0.00%)
Osteoarthritis † 1	2/58 (3.45%)	0/115 (0.00%)	0/58 (0.00%)	8/51 (15.69%)	7/106 (6.60%)	3/48 (6.25%)
Pain in extremity † 1	2/58 (3.45%)	4/115 (3.48%)	3/58 (5.17%)	2/51 (3.92%)	3/106 (2.83%)	1/48 (2.08%)
Nervous system disorders
Dizziness † 1	4/58 (6.90%)	1/115 (0.87%)	4/58 (6.90%)	4/51 (7.84%)	5/106 (4.72%)	4/48 (8.33%)
Headache † 1	4/58 (6.90%)	10/115 (8.70%)	5/58 (8.62%)	3/51 (5.88%)	6/106 (5.66%)	4/48 (8.33%)
Psychiatric disorders
Depression † 1	0/58 (0.00%)	2/115 (1.74%)	1/58 (1.72%)	1/51 (1.96%)	7/106 (6.60%)	0/48 (0.00%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	0/58 (0.00%)	3/115 (2.61%)	1/58 (1.72%)	9/51 (17.65%)	9/106 (8.49%)	1/48 (2.08%)
Skin and subcutaneous tissue disorders
Dry skin † 1	1/58 (1.72%)	0/115 (0.00%)	1/58 (1.72%)	3/51 (5.88%)	0/106 (0.00%)	0/48 (0.00%)
Rash † 1	0/58 (0.00%)	1/115 (0.87%)	3/58 (5.17%)	0/51 (0.00%)	3/106 (2.83%)	1/48 (2.08%)
Vascular disorders
Hypertension † 1	2/58 (3.45%)	1/115 (0.87%)	2/58 (3.45%)	2/51 (3.92%)	8/106 (7.55%)	2/48 (4.17%)
1 Term from vocabulary, MedDRA 20.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

The systematic randomization error was not anticipated to have an impact on the power of the study. The sample size to detect a difference in efficacy endpoints was reached (it was increased to obtain additional safety data) and blind was maintained.

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:

Stroes E, Guyton JR, Lepor N, Civeira F, Gaudet D, Watts GF, Baccara-Dinet MT, Lecorps G, Manvelian G, Farnier M; ODYSSEY CHOICE II Investigators. Efficacy and Safety of Alirocumab 150 mg Every 4 Weeks in Patients With Hypercholesterolemia Not on Statin Therapy: The ODYSSEY CHOICE II Study. J Am Heart Assoc. 2016 Sep 13;5(9). pii: e003421. doi: 10.1161/JAHA.116.003421.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT02023879 History of Changes
• Other Study ID Numbers: EFC13786; 2013-002659-14 ( EudraCT Number ); U1111-1146-3517 ( Other Identifier: UTN )
• First Submitted: December 6, 2013
• First Posted: December 30, 2013
• Results First Submitted: January 24, 2017
• Results First Posted: March 15, 2017
• Last Update Posted: July 27, 2018