Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With High Cardiovascular Risk and Hypercholesterolemia (ODYSSEY COMBO I)

• ClinicalTrials.gov Identifier: NCT01644175
• Recruitment Status: Completed
• First Posted: July 18, 2012
• Results First Posted: November 6, 2015
• Last Update Posted: November 6, 2015
• Sponsor: Sanofi
• Collaborator: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Sanofi

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Hypercholesterolemia
• Interventions: Drug: Placebo (for alirocumab); Drug: Alirocumab; Drug: Lipid-Modifying Therapy (LMT)
• Enrollment: 316

Participant Flow

Recruitment Details	The study was conducted at 76 centers in the United States of America. Overall, 640 participants were screened between July 2012 and February 2013, 324 of whom were screen failures. Screen failures were mainly due to exclusion criteria met.
Pre-assignment Details	Randomization was stratified according to prior history of myocardial infarction (MI) or ischemic stroke, and intensity of statin treatment. Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 1:2 ratio (placebo: alirocumab) after confirmation of selection criteria. 316 participants were randomized.

Arm/Group Title	Placebo Q2W	Alirocumab 75/150 mg Q2W
Arm/Group Description	Placebo (for alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable Lipid-Modifying Therapy (LMT) for 52 weeks.	Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Period Title: Overall Study
Started	107 [1]	209 [1]
Treated	107	207
Completed	75	156
Not Completed	32	53
Reason Not Completed
Randomized But Not Treated	0	2
Adverse Event	8	13
Death	1	2
Poor compliance to protocol	9	10
Physician Decision	1	2
Participant Moved	1	2
Consent withdrawn by participant	3	4
Related to Autoinjector Administration	2	1
Last visit outside protocol visit window	4	11
Selection criteria finally not met	0	1
Site closure	2	2
Lost to Follow-up	1	0
Other than specified above	0	3
[1] Randomized

Baseline Characteristics

Arm/Group Title		Placebo Q2W	Alirocumab 75/150 mg Q2W	Total
Arm/Group Description		Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Total of all reporting groups
Overall Number of Baseline Participants		107	209	316
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	107 participants	209 participants	316 participants
		63.0 (8.8)	63.0 (9.5)	63.0 (9.3)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	107 participants	209 participants	316 participants
	Female	30 28.0%	78 37.3%	108 34.2%
	Male	77 72.0%	131 62.7%	208 65.8%
Calculated LDL-C in mmol/L [1]; Mean (Standard Deviation); Unit of measure: mmol/L
	Number Analyzed	107 participants	209 participants	316 participants
		2.746 (0.915)	2.595 (0.764)	2.646 (0.820)
		[1] Measure Description: Calculated LDL-C in mmol/L from Friedewald formula (LDL cholesterol = Total cholesterol - HDL cholesterol - [Triglyceride/2.2]).
Calculated LDL-C in mg/dL [1]; Mean (Standard Deviation); Unit of measure: mg/dL
	Number Analyzed	107 participants	209 participants	316 participants
		106.0 (35.3)	100.2 (29.5)	102.2 (31.6)
		[1] Measure Description: Calculated LDL-C in mg/dL from Friedewald formula (LDL cholesterol = Total cholesterol - HDL cholesterol - [Triglyceride/5]).

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 52 regardless of status on- or off-treatment were used in the model (ITT analysis).
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo Q2W	Alirocumab 75/150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed	106	205
Least Squares Mean (Standard Error); Unit of Measure: percent change
	-2.3 (2.7)	-48.2 (1.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 75/150 mg Q2W
	Comments	Alirocumab group was compared to placebo group using an appropriate contrast statement.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-45.9
	Confidence Interval	(2-Sided) 95%; -52.5 to -39.3
	Estimation Comments	Alirocumab 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 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection) (on-treatment analysis).
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo Q2W	Alirocumab 75/150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed	105	204
Least Squares Mean (Standard Error); Unit of Measure: percent change
	-0.8 (2.6)	-50.7 (1.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 75/150 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 was ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-49.9
	Confidence Interval	(2-Sided) 95%; -56.2 to -43.6
	Estimation Comments	Alirocumab 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 model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75/150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed	106	205
Least Squares Mean (Standard Error); Unit of Measure: percent change
	1.1 (2.5)	-46.3 (1.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 75/150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-47.4
	Confidence Interval	(2-Sided) 95%; -53.6 to -41.3
	Estimation Comments	Alirocumab 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 52 (i.e. up to 21 days after last injection).
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75/150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed	105	204
Least Squares Mean (Standard Error); Unit of Measure: percent change
	1.7 (2.5)	-47.6 (1.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 75/150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-49.3
	Confidence Interval	(2-Sided) 95%; -55.3 to -43.3
	Estimation Comments	Alirocumab vs. placebo

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo Q2W	Alirocumab 75/150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed	96	185
Least Squares Mean (Standard Error); Unit of Measure: percent change
	-0.9 (2.3)	-36.7 (1.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 75/150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-35.8
	Confidence Interval	(2-Sided) 95%; -41.3 to -30.3
	Estimation Comments	Alirocumab vs. placebo

6. 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 52 (i.e. up to 21 days after last injection).
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo Q2W	Alirocumab 75/150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed	93	181
Least Squares Mean (Standard Error); Unit of Measure: percent change
	-0.4 (2.3)	-37.9 (1.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 75/150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-37.5
	Confidence Interval	(2-Sided) 95%; -43.0 to -32.0
	Estimation Comments	Alirocumab vs. placebo

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo Q2W	Alirocumab 75/150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed	106	205
Least Squares Mean (Standard Error); Unit of Measure: percent change
	-1.6 (2.5)	-39.1 (1.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 75/150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-37.5
	Confidence Interval	(2-Sided) 95%; -43.5 to -31.4
	Estimation Comments	Alirocumab vs. placebo

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo Q2W	Alirocumab 75/150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed	105	204
Least Squares Mean (Standard Error); Unit of Measure: percent change
	-0.5 (2.5)	-40.9 (1.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 75/150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-40.4
	Confidence Interval	(2-Sided) 95%; -46.4 to -34.4
	Estimation Comments	Alirocumab vs. placebo

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo Q2W	Alirocumab 75/150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed	106	205
Least Squares Mean (Standard Error); Unit of Measure: percent change
	-2.9 (1.8)	-27.9 (1.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 75/150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-25.0
	Confidence Interval	(2-Sided) 95%; -29.3 to -20.7
	Estimation Comments	Alirocumab vs. placebo

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Apo B ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75/150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed	96	185
Least Squares Mean (Standard Error); Unit of Measure: percent change
	3.4 (2.3)	-34.8 (1.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 75/150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-38.2
	Confidence Interval	(2-Sided) 95%; -43.7 to -32.7
	Estimation Comments	Alirocumab vs. placebo

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Non-HDL-C ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75/150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed	106	205
Least Squares Mean (Standard Error); Unit of Measure: percent change
	2.6 (2.6)	-37.4 (1.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 75/150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-40.1
	Confidence Interval	(2-Sided) 95%; -46.2 to -33.9
	Estimation Comments	Alirocumab vs. placebo

12. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Total-C ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75/150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed	106	205
Least Squares Mean (Standard Error); Unit of Measure: percent change
	0.9 (2.0)	-25.4 (1.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 75/150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-26.4
	Confidence Interval	(2-Sided) 95%; -31.1 to -21.7
	Estimation Comments	Alirocumab vs. placebo

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75/150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed	106	205
Least Squares Mean (Standard Error); Unit of Measure: percent change
	0.5 (3.6)	-42.5 (2.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 75/150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-43.0
	Confidence Interval	(2-Sided) 95%; -51.6 to -34.3
	Estimation Comments	Alirocumab vs. placebo

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75/150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed	106	205
Measure Type: Number; Unit of Measure: percentage of participants
	9.0	75.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 75/150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Regression, Logistic
	Comments	Multiple imputation approach followed by logistic regression model.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	38.5
	Confidence Interval	(2-Sided) 95%; 16.5 to 89.8
	Estimation Comments	Alirocumab vs. placebo

15. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75/150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed	105	204
Measure Type: Number; Unit of Measure: percentage of participants
	8.0	77.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 75/150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05
	Method	Regression, Logistic
	Comments	Multiple imputation approach followed by logistic regression model
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	50.0
	Confidence Interval	(2-Sided) 95%; 20.6 to 121.0
	Estimation Comments	Alirocumab vs. placebo

16. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75/150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed	106	205
Mean (Standard Error); Unit of Measure: percent change
	-5.9 (2.8)	-20.5 (2.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 75/150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Regression, Robust
	Comments	Multiple imputation approach followed by a robust regression model.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-14.6
	Confidence Interval	(2-Sided) 95%; -21.3 to -7.9
	Estimation Comments	Alirocumab vs. placebo

17. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo Q2W	Alirocumab 75/150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed	106	205
Least Squares Mean (Standard Error); Unit of Measure: percent change
	-3.8 (1.5)	3.5 (1.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 75/150 mg Q2W
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	7.3
	Confidence Interval	(2-Sided) 95%; 3.6 to 11.0
	Estimation Comments	Alirocumab vs. placebo

18. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75/150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed	106	205
Mean (Standard Error); Unit of Measure: percent change
	-5.4 (3.2)	-6.0 (2.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q2W, Alirocumab 75/150 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	0.8699
	Comments	Threshold for significance ≤ 0.05.
	Method	Regression, Robust
	Comments	Multiple imputation approach followed by a robust regression model.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -8.3 to 7.0
	Estimation Comments	Alirocumab vs. placebo

19. Secondary Outcome

Title	Percent Change From Baseline in Apolipoprotein A-1 at Week 24 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Participants of the ITT population with one baseline and at least one post-baseline Apo A-1 value on- or off-treatment (Apo A-1 ITT population).

Arm/Group Title	Placebo Q2W	Alirocumab 75/150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed	96	185
Least Squares Mean (Standard Error); Unit of Measure: percent change
	-2.5 (1.2)	3.3 (0.9)

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 multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75/150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed	106	205
Mean (Standard Error); Unit of Measure: percent change
	0.0 (2.7)	-19.7 (1.9)

21. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

HDL-C ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75/150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed	106	205
Least Squares Mean (Standard Error); Unit of Measure: percent change
	-2.4 (1.4)	6.7 (1.0)

22. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75/150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed	106	205
Mean (Standard Error); Unit of Measure: percent change
	3.0 (2.9)	-11.3 (2.0)

23. 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 model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Apo A-1 ITT population.

Arm/Group Title	Placebo Q2W	Alirocumab 75/150 mg Q2W
Arm/Group Description:	Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed	96	185
Least Squares Mean (Standard Error); Unit of Measure: percent change
	-1.8 (1.3)	3.8 (0.9)

Adverse Events

Time Frame	All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description	Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Arm/Group Title	Placebo Q2W	Alirocumab 75 /up to 150 mg Q2W
Arm/Group Description	Participants exposed to placebo (for alirocumab) SC injection Q2W added to stable LMT (mean exposition of 45 weeks).	Participants exposed to alirocumab 75 mg /up to 150 mg SC injection Q2W added to stable LMT (mean exposition of 46 weeks).
All-Cause Mortality
	Placebo Q2W	Alirocumab 75 /up to 150 mg Q2W
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Placebo Q2W	Alirocumab 75 /up to 150 mg Q2W
	Affected / at Risk (%)	Affected / at Risk (%)
Total	14/107 (13.08%)	26/207 (12.56%)
Cardiac disorders
Angina pectoris † 1	0/107 (0.00%)	1/207 (0.48%)
Coronary artery disease † 1	0/107 (0.00%)	2/207 (0.97%)
Acute myocardial infarction † 1	0/107 (0.00%)	2/207 (0.97%)
Atrial fibrillation † 1	1/107 (0.93%)	0/207 (0.00%)
Cardiac failure congestive † 1	0/107 (0.00%)	1/207 (0.48%)
Ventricular tachycardia † 1	0/107 (0.00%)	1/207 (0.48%)
Atrial flutter † 1	1/107 (0.93%)	0/207 (0.00%)
Intracardiac thrombus † 1	1/107 (0.93%)	0/207 (0.00%)
Ischaemic cardiomyopathy † 1	1/107 (0.93%)	0/207 (0.00%)
Myocardial infarction † 1	1/107 (0.93%)	0/207 (0.00%)
Eye disorders
Retinal detachment † 1	0/107 (0.00%)	1/207 (0.48%)
Gastrointestinal disorders
Gastrooesophageal reflux disease † 1	1/107 (0.93%)	0/207 (0.00%)
Ileus † 1	0/107 (0.00%)	1/207 (0.48%)
Intussusception † 1	0/107 (0.00%)	1/207 (0.48%)
Enteritis † 1	1/107 (0.93%)	0/207 (0.00%)
Mesenteric vein thrombosis † 1	1/107 (0.93%)	0/207 (0.00%)
Small intestinal obstruction † 1	1/107 (0.93%)	0/207 (0.00%)
Upper gastrointestinal haemorrhage † 1	1/107 (0.93%)	0/207 (0.00%)
General disorders
Chest pain † 1	0/107 (0.00%)	1/207 (0.48%)
Non-cardiac chest pain † 1	3/107 (2.80%)	0/207 (0.00%)
Sudden cardiac death † 1	1/107 (0.93%)	0/207 (0.00%)
Infections and infestations
Bronchitis † 1	0/107 (0.00%)	1/207 (0.48%)
Gastroenteritis † 1	1/107 (0.93%)	0/207 (0.00%)
Osteomyelitis † 1	0/107 (0.00%)	1/207 (0.48%)
Subcutaneous abscess † 1	0/107 (0.00%)	1/207 (0.48%)
Clostridium difficile infection † 1	1/107 (0.93%)	0/207 (0.00%)
Wound infection † 1	1/107 (0.93%)	0/207 (0.00%)
Injury, poisoning and procedural complications
Fall † 1	1/107 (0.93%)	1/207 (0.48%)
Traumatic haematoma † 1	0/107 (0.00%)	1/207 (0.48%)
Intentional overdose † 1	0/107 (0.00%)	1/207 (0.48%)
Wound † 1	1/107 (0.93%)	0/207 (0.00%)
Jaw fracture † 1	1/107 (0.93%)	0/207 (0.00%)
Muscle rupture † 1	1/107 (0.93%)	0/207 (0.00%)
Postoperative ileus † 1	1/107 (0.93%)	0/207 (0.00%)
Tooth injury † 1	1/107 (0.93%)	0/207 (0.00%)
Metabolism and nutrition disorders
Hypokalaemia † 1	0/107 (0.00%)	1/207 (0.48%)
Musculoskeletal and connective tissue disorders
Osteoarthritis † 1	0/107 (0.00%)	1/207 (0.48%)
Pain in extremity † 1	1/107 (0.93%)	1/207 (0.48%)
Intervertebral disc protrusion † 1	0/107 (0.00%)	1/207 (0.48%)
Muscle spasms † 1	0/107 (0.00%)	1/207 (0.48%)
Muscular weakness † 1	0/107 (0.00%)	1/207 (0.48%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon adenoma † 1	1/107 (0.93%)	0/207 (0.00%)
Transitional cell carcinoma † 1	0/107 (0.00%)	1/207 (0.48%)
Chronic myeloid leukaemia † 1	1/107 (0.93%)	0/207 (0.00%)
Oesophageal adenocarcinoma metastatic † 1	1/107 (0.93%)	0/207 (0.00%)
Nervous system disorders
Syncope † 1	0/107 (0.00%)	1/207 (0.48%)
Cerebrovascular accident † 1	0/107 (0.00%)	1/207 (0.48%)
Ischaemic stroke † 1	0/107 (0.00%)	1/207 (0.48%)
Dementia † 1	1/107 (0.93%)	0/207 (0.00%)
Hypoglycaemic coma † 1	1/107 (0.93%)	0/207 (0.00%)
Psychiatric disorders
Suicide attempt † 1	0/107 (0.00%)	1/207 (0.48%)
Renal and urinary disorders
Renal failure acute † 1	1/107 (0.93%)	0/207 (0.00%)
Renal failure † 1	1/107 (0.93%)	1/207 (0.48%)
Respiratory, thoracic and mediastinal disorders
Asthma † 1	0/107 (0.00%)	2/207 (0.97%)
Dyspnoea † 1	0/107 (0.00%)	1/207 (0.48%)
Interstitial lung disease † 1	0/107 (0.00%)	1/207 (0.48%)
Pulmonary embolism † 1	0/107 (0.00%)	1/207 (0.48%)
Vascular disorders
Hypertension † 1	0/107 (0.00%)	1/207 (0.48%)
Extremity necrosis † 1	0/107 (0.00%)	1/207 (0.48%)
Peripheral ischaemia † 1	0/107 (0.00%)	1/207 (0.48%)
Thrombosis † 1	0/107 (0.00%)	1/207 (0.48%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 17.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo Q2W	Alirocumab 75 /up to 150 mg Q2W
	Affected / at Risk (%)	Affected / at Risk (%)
Total	31/107 (28.97%)	72/207 (34.78%)
General disorders
Injection site reaction † 1	3/107 (2.80%)	11/207 (5.31%)
Infections and infestations
Upper respiratory tract infection † 1	11/107 (10.28%)	16/207 (7.73%)
Nasopharyngitis † 1	5/107 (4.67%)	15/207 (7.25%)
Urinary tract infection † 1	4/107 (3.74%)	13/207 (6.28%)
Sinusitis † 1	4/107 (3.74%)	11/207 (5.31%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	8/107 (7.48%)	8/207 (3.86%)
Nervous system disorders
Dizziness † 1	6/107 (5.61%)	11/207 (5.31%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 17.0

Limitations and Caveats

[Not Specified]

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:

Kereiakes DJ, Robinson JG, Cannon CP, Lorenzato C, Pordy R, Chaudhari U, Colhoun HM. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: The ODYSSEY COMBO I study. Am Heart J. 2015 Jun;169(6):906-915.e13. doi: 10.1016/j.ahj.2015.03.004. Epub 2015 Mar 13.

Other Publications:

Colhoun HM, Robinson JG, Farnier M, Cariou B, Blom D, Kereiakes DJ, Lorenzato C, Pordy R, Chaudhari U. Efficacy and safety of alirocumab, a fully human PCSK9 monoclonal antibody, in high cardiovascular risk patients with poorly controlled hypercholesterolemia on maximally tolerated doses of statins: rationale and design of the ODYSSEY COMBO I and II trials. BMC Cardiovasc Disord. 2014 Sep 20;14:121. doi: 10.1186/1471-2261-14-121.

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.

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

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT01644175
• Other Study ID Numbers: EFC11568; U1111-1121-4356 ( Other Identifier: UTN )
• First Submitted: July 16, 2012
• First Posted: July 18, 2012
• Results First Submitted: August 20, 2015
• Results First Posted: November 6, 2015
• Last Update Posted: November 6, 2015