Evaluation of Alirocumab Versus Ezetimibe on Top of Stati... | NCT02715726

ID	Type	Description	Link
U1111-1150-8859	Other Identifier	UTN

Name	Class
Regeneron Pharmaceuticals	INDUSTRY

Label	Type	Description	Intervention Names
Ezetimibe 10 mg	Active Comparator	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab every 2 weeks (Q2W) for 22 weeks added to lipid modifying therapy (LMT).	Drug: Placebo for alirocumab Drug: ezetimibe Drug: atorvastatin Drug: rosuvastatin Drug: simvastatin
Alirocumab 75 mg Q2W/up to 150 mg Q2W	Experimental	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 milligrams per deciliter (mg/dL) (1.81 millimoles per liter [mmol/L]) at Week 8.	Drug: Alirocumab Drug: placebo for ezetimibe Drug: atorvastatin Drug: rosuvastatin Drug: simvastatin

Name	Type	Description	Arm Group Labels	Other Names
Alirocumab	Drug	Pharmaceutical form:solution Route of administration: subcutaneous	Alirocumab 75 mg Q2W/up to 150 mg Q2W

Measure	Description	Time Frame
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 24: Intent-to-treat (ITT) Analysis	Adjusted least square (LS) means and standard errors at Week 24 were obtained from mixed models analysis 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).	From Baseline to Week 24

Measure	Description	Time Frame
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 24: On-Treatment Analysis	Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first) (on-treatment analysis).	From Baseline to Week 24

Eligibility Module

Eligibility Criteria

Inclusion criteria:

Participants with hypercholesterolemia and established coronary heart disease (CHD) or CHD risk equivalents who are not adequately controlled with a maximally tolerated daily dose of statin at a stable dose for at least 4 weeks prior to the screening visit (Week -3).

Exclusion criteria:

Participants without established CHD or CHD risk equivalents.
LDL-C <70 mg/dL (<1.81 mmol/L) at the screening visit (Week -3) in participants with history of documented CV disease.
LDL-C <100 mg/dL (<2.59 mmol/L) at the screening visit (Week -3) in participants without history of documented CV disease.
Change in statin dose or dose regimen from screening to randomization.
Currently taking a statin other than atorvastatin, rosuvastatin, or simvastatin.
Atorvastatin, rosuvastatin, or simvastatin was not taken daily or not taken at a registered dose.
Daily doses above atorvastatin 80 mg, rosuvastatin 40 mg, or simvastatin 40 mg.
Use of cholesterol absorption inhibitor (ie, ezetimibe), omega-3 fatty acid (at doses ≥1000 mg daily), nicotinic acid, fibrates, bile acid-binding sequestrant, or red yeast rice products in the past 4 weeks prior to screening visit (Week -3).
Fasting serum triglycerides >400 mg/dL (>4.52 mmol/L) at the screening period.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Name	Affiliation	Role
Clinical Sciences & Operations	Sanofi	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Investigational Site Number 1560027		Beijing		100029	China
Investigational Site Number 1560043

PubMed Identifier	Type	Citation	Retractions
31882376	Derived	Han Y, Chen J, Chopra VK, Zhang S, Su G, Ma C, Huang Z, Ma Y, Yao Z, Yuan Z, Zhao Q, Kuanprasert S, Baccara-Dinet MT, Manvelian G, Li J, Chen R. ODYSSEY EAST: Alirocumab efficacy and safety vs ezetimibe in high cardiovascular risk patients with hypercholesterolemia and on maximally tolerated statin in China, India, and Thailand. J Clin Lipidol. 2020 Jan-Feb;14(1):98-108.e8. doi: 10.1016/j.jacl.2019.10.015. Epub 2019 Nov 18.

ID	Title	Description
FG000	Ezetimibe 10 mg	Oral ezetimibe 10 mg capsule once daily with or without food for 24 Weeks and subcutaneous placebo injection for alirocumab every 2 weeks (Q2W) for 22 weeks added to lipid modifying therapy (LMT).
FG001	Alirocumab 75 mg Q2W/up to 150 mg Q2W

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Oct 17, 2017	Jul 19, 2019

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 24: Intent-to-treat (ITT) Analysis

Adjusted least square (LS) means and standard errors at Week 24 were obtained from mixed models analysis 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).

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

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 24

ID	Title	Description
OG000	Ezetimibe 10 mg	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab Q2W for 22 weeks added to LMT.
OG001	Alirocumab 75 mg Q2W/up to 150 mg Q2W	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 mg/dL (1.81 mmol/L) at Week 8.

Units	Counts
Participants	OG000208 OG001403

Title

Denominators

Categories

Title	Measurements
	OG000-20.3± 2.0 OG001-56.0± 1.5

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Alirocumab group was compared to ezetimibe group using an appropriate contrast statement.	Mixed Models Analysis		<0.0001	Threshold for significance at 0.05 level.	LS mean difference	-35.6			2-Sided	95	-40.6	-30.7			Alirocumab 75 mg Q2W/up to 150 mg Q2W vs. Ezetimibe		Superiority

Secondary

Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 24: On-Treatment Analysis

Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first) (on-treatment analysis).

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

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 24

ID	Title	Description
OG000	Ezetimibe 10 mg	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab Q2W for 22 weeks added to LMT.
OG001	Alirocumab 75 mg Q2W/up to 150 mg Q2W	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 mg/dL (1.81 mmol/L) at Week 8.

Units	Counts

Secondary

Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 12: ITT Analysis

Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

ITT population.

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 12

ID	Title	Description
OG000	Ezetimibe 10 mg	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab Q2W for 22 weeks added to LMT.
OG001	Alirocumab 75 mg Q2W/up to 150 mg Q2W	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 mg/dL (1.81 mmol/L) at Week 8.

Units	Counts
Participants

Secondary

Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 12: On-Treatment Analysis

Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first) (on-treatment analysis).

mITT population.

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 12

ID	Title	Description
OG000	Ezetimibe 10 mg	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab Q2W for 22 weeks added to LMT.
OG001	Alirocumab 75 mg Q2W/up to 150 mg Q2W	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 mg/dL (1.81 mmol/L) at Week 8.

Units	Counts
Participants

Secondary

Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24: ITT Analysis

Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

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).

Posted

Least Squares Mean

Standard Error

percent Change

From Baseline to Week 24

ID	Title	Description
OG000	Ezetimibe 10 mg	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab Q2W for 22 weeks added to LMT.
OG001	Alirocumab 75 mg Q2W/up to 150 mg Q2W	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 mg/dL (1.81 mmol/L) at Week 8.

Units	Counts
Participants

Secondary

Percent Change From Baseline in Apolipoprotein B at Week 24: On-Treatment Analysis

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

Posted

Least Squares Mean

Standard Error

percent Change

From Baseline to Week 24

ID	Title	Description
OG000	Ezetimibe 10 mg	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab Q2W for 22 weeks added to LMT.
OG001	Alirocumab 75 mg Q2W/up to 150 mg Q2W	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 mg/dL (1.81 mmol/L) at Week 8.

Units	Counts
Participants

Secondary

Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24: ITT Analysis

Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

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).

Posted

Least Squares Mean

Standard Error

percent Change

From Baseline to Week 24

ID	Title	Description
OG000	Ezetimibe 10 mg	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab Q2W for 22 weeks added to LMT.
OG001	Alirocumab 75 mg Q2W/up to 150 mg Q2W	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 mg/dL (1.81 mmol/L) at Week 8.

Units	Counts
Participants

Secondary

Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 24: On-Treatment Analysis

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).

Posted

Least Squares Mean

Standard Error

percent Change

From Baseline to Week 24

ID	Title	Description
OG000	Ezetimibe 10 mg	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab Q2W for 22 weeks added to LMT.
OG001	Alirocumab 75 mg Q2W/up to 150 mg Q2W	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 mg/dL (1.81 mmol/L) at Week 8.

Units	Counts

Secondary

Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24: ITT Analysis

Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline data from Week 4 up to Week 24 regardless of status on- or off-treatment.

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

Posted

Least Squares Mean

Standard Error

percent Change

From Baseline to Week 24

ID	Title	Description
OG000	Ezetimibe 10 mg	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab Q2W for 22 weeks added to LMT.
OG001	Alirocumab 75 mg Q2W/up to 150 mg Q2W	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 mg/dL (1.81 mmol/L) at Week 8.

Units	Counts
Participants

Secondary

Percent Change From Baseline in Apolipoprotein B at Week 12: ITT Analysis

Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Apo B ITT population.

Posted

Least Squares Mean

Standard Error

percent Change

From Baseline to Week 12

ID	Title	Description
OG000	Ezetimibe 10 mg	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab Q2W for 22 weeks added to LMT.
OG001	Alirocumab 75 mg Q2W/up to 150 mg Q2W	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 mg/dL (1.81 mmol/L) at Week 8.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 12: ITT Analysis

Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Non-HDL-C ITT population.

Posted

Least Squares Mean

Standard Error

percent Change

From Baseline to Week 12

ID	Title	Description
OG000	Ezetimibe 10 mg	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab Q2W for 22 weeks added to LMT.
OG001	Alirocumab 75 mg Q2W/up to 150 mg Q2W	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 mg/dL (1.81 mmol/L) at Week 8.

Units	Counts
Participants

Secondary

Percent Change From Baseline in Total Cholesterol at Week 12: ITT Analysis

Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Total-C ITT population

Posted

Least Squares Mean

Standard Error

percent Change

From Baseline to Week 12

ID	Title	Description
OG000	Ezetimibe 10 mg	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab Q2W for 22 weeks added to LMT.
OG001	Alirocumab 75 mg Q2W/up to 150 mg Q2W	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 mg/dL (1.81 mmol/L) at Week 8.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants Reaching Calculated Low Density Lipoprotein Cholesterol <70 mg/dL (1.81 mmol/L) at Week 24: ITT Analysis

Adjusted percentages at Week 24 were obtained from multiple imputation approach for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model.

ITT population.

Posted

Number

percentage of participants

Up to Week 24

ID	Title	Description
OG000	Ezetimibe 10 mg	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab Q2W for 22 weeks added to LMT.
OG001	Alirocumab 75 mg Q2W/up to 150 mg Q2W	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 mg/dL (1.81 mmol/L) at Week 8.

Units	Counts
Participants

Secondary

Percentage of Participants Reaching Calculated Low Density Lipoprotein Cholesterol <70 mg/dL (1.81 mmol/L) at Week 24: On-Treatment Analysis

Adjusted percentages at Week 24 were obtained from multiple imputation approach including all available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first) (on-treatment analysis).

mITT population.

Posted

Number

percentage of participants

Up to Week 24

ID	Title	Description
OG000	Ezetimibe 10 mg	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab Q2W for 22 weeks added to LMT.
OG001	Alirocumab 75 mg Q2W/up to 150 mg Q2W	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 mg/dL (1.81 mmol/L) at Week 8.

Units	Counts
Participants

Secondary

Percent Change From Baseline in Lipoprotein (a) (Lp[a]) at Week 24: ITT Analysis

Adjusted means and standard errors at Week 24 were obtained from multiple imputation approach followed by robust regression model for handling missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model.

ITT population.

Posted

Mean

Standard Error

percent Change

From Baseline to Week 24

ID	Title	Description
OG000	Ezetimibe 10 mg	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab Q2W for 22 weeks added to LMT.
OG001	Alirocumab 75 mg Q2W/up to 150 mg Q2W	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 mg/dL (1.81 mmol/L) at Week 8.

Units	Counts
Participants

Secondary

Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 24: ITT Analysis

Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

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).

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 24

ID	Title	Description
OG000	Ezetimibe 10 mg	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab Q2W for 22 weeks added to LMT.
OG001	Alirocumab 75 mg Q2W/up to 150 mg Q2W	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 mg/dL (1.81 mmol/L) at Week 8.

Units	Counts
Participants

Secondary

Percent Change From Baseline in Fasting Triglycerides (TG) at Week 24: ITT Analysis

Adjusted means and standard errors at Week 24 were obtained by using 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.

ITT population.

Posted

Mean

Standard Error

percent change

From Baseline to Week 24

ID	Title	Description
OG000	Ezetimibe 10 mg	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab Q2W for 22 weeks added to LMT.
OG001	Alirocumab 75 mg Q2W/up to 150 mg Q2W	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 mg/dL (1.81 mmol/L) at Week 8.

Units	Counts
Participants

Secondary

Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24: ITT Analysis

Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Participants from 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).

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 24

ID	Title	Description
OG000	Ezetimibe 10 mg	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab Q2W for 22 weeks added to LMT.
OG001	Alirocumab 75 mg Q2W/up to 150 mg Q2W	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 mg/dL (1.81 mmol/L) at Week 8.

Units	Counts
Participants

Secondary

Percent Change From Baseline in Lipoprotein (a) at Week 12: ITT Analysis

Adjusted means and standard errors at Week 12 were obtained from 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.

ITT population.

Posted

Mean

Standard Error

percent Change

From Baseline to Week 12

ID	Title	Description
OG000	Ezetimibe 10 mg	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab Q2W for 22 weeks added to LMT.
OG001	Alirocumab 75 mg Q2W/up to 150 mg Q2W	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 mg/dL (1.81 mmol/L) at Week 8.

Units	Counts
Participants

Secondary

Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 12: ITT Analysis

Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

HDL-C ITT population.

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 12

ID	Title	Description
OG000	Ezetimibe 10 mg	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab Q2W for 22 weeks added to LMT.
OG001	Alirocumab 75 mg Q2W/up to 150 mg Q2W	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 mg/dL (1.81 mmol/L) at Week 8.

Units	Counts
Participants

Secondary

Percent Change From Baseline in Fasting Triglycerides at Week 12: ITT Analysis

Adjusted means and standard errors at Week 12 were obtained by using multiple imputation approach followed by a robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

ITT population.

Posted

Mean

Standard Error

percent change

From Baseline to Week 12

ID	Title	Description
OG000	Ezetimibe 10 mg	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab Q2W for 22 weeks added to LMT.
OG001	Alirocumab 75 mg Q2W/up to 150 mg Q2W	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 mg/dL (1.81 mmol/L) at Week 8.

Units	Counts
Participants

Secondary

Percent Change From Baseline in Apolipoprotein A-1 at Week 12 : ITT Analysis

Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Apo A-1 ITT population.

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 12

ID	Title	Description
OG000	Ezetimibe 10 mg	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab Q2W for 22 weeks added to LMT.
OG001	Alirocumab 75 mg Q2W/up to 150 mg Q2W	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 mg/dL (1.81 mmol/L) at Week 8.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute Coronary Syndrome	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected206 at risk EG0011 events1 affected406 at risk
Acute Myocardial Infarction	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0003 events3 affected206 at risk EG0013 events3 affected406 at risk
Angina Unstable	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0019 events9 affected406 at risk
Arrhythmia Supraventricular	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected406 at risk
Arteriosclerosis Coronary Artery	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected206 at risk EG0012 events2 affected406 at risk
Atrial Fibrillation	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected406 at risk
Cardiac Failure	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected206 at risk EG0012 events2 affected406 at risk
Cardiac Failure Acute	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Cardiac Failure Congestive	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0003 events2 affected206 at risk EG0010 events0 affected406 at risk
Cardio-Respiratory Arrest	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected406 at risk
Coronary Artery Disease	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Myocardial Ischaemia	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected406 at risk
Sudden Hearing Loss	Ear and labyrinth disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected406 at risk
Cataract	Eye disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected406 at risk
Gastrointestinal Haemorrhage	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected406 at risk
Gastrointestinal Perforation	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected406 at risk
Haemorrhagic Erosive Gastritis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Obstructive Pancreatitis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected406 at risk
Tongue Haemorrhage	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected406 at risk
Upper Gastrointestinal Haemorrhage	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected406 at risk
Death	General disorders	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected206 at risk EG0010 events0 affected406 at risk
Non-Cardiac Chest Pain	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected406 at risk
Anal Abscess	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Appendicitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Bronchitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0012 events2 affected406 at risk
Lung Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected206 at risk EG0011 events1 affected406 at risk
Necrotising Soft Tissue Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Pneumonia	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0015 events4 affected406 at risk
Sepsis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected406 at risk
Tuberculosis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Brain Herniation	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Femoral Neck Fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Femur Fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Spinal Compression Fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Subarachnoid Haemorrhage	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Alanine Aminotransferase Increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Diabetes Mellitus	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected406 at risk
Intervertebral Disc Protrusion	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0012 events2 affected406 at risk
Limb Mass	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Lumbar Spinal Stenosis	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Lung Adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected406 at risk
Prostate Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Small Cell Lung Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Brain Oedema	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Cerebral Arteriosclerosis	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Cerebral Artery Occlusion	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Cerebral Infarction	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0012 events1 affected406 at risk
Cerebral Ischaemia	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Cerebrovascular Insufficiency	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Coma	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Ischaemic Cerebral Infarction	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Ischaemic Stroke	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected206 at risk EG0010 events0 affected406 at risk
Loss Of Consciousness	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected406 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Ureterolithiasis	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Adnexa Uteri Cyst	Reproductive system and breast disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Benign Prostatic Hyperplasia	Reproductive system and breast disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0012 events1 affected406 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Lung Disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected406 at risk
Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk
Upper-Airway Cough Syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected406 at risk
Peripheral Arterial Occlusive Disease	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected406 at risk

ID	Term
D006949	Hyperlipidemias
D050171	Dyslipidemias
D052439	Lipid Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases

ID	Term
C571059	alirocumab
D000069438	Ezetimibe
D000069059	Atorvastatin
D000068718	Rosuvastatin Calcium
D019821	Simvastatin

ID	Term
D001384	Azetidines
D001385	Azetines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D011758	Pyrroles
D001393	Azoles
D006538	Heptanoic Acids
D005227	Fatty Acids
D008055	Lipids
D013449	Sulfonamides
D000577	Amides
D009930	Organic Chemicals
D005464	Fluorobenzenes
D006845	Hydrocarbons, Fluorinated
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D013450	Sulfones
D013457	Sulfur Compounds
D011743	Pyrimidines
D008148	Lovastatin
D009281	Naphthalenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D011083	Polycyclic Compounds

ID	Title	Description
BG000	Ezetimibe 10 mg	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab Q2W for 22 weeks added to LMT.
BG001	Alirocumab 75 mg Q2W/up to 150 mg Q2W	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 mg/dL (1.81 mmol/L) at Week 8.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Ezetimibe 10 mg	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab Q2W for 22 weeks added to LMT.	3	206	23	206	41	206
EG001	Alirocumab 75 mg Q2W/up150 mg Q2W	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 mg/dL (1.81 mmol/L) at Week 8.	2	406	41	406	71	406

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Upper Respiratory Tract Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG00039 events29 affected206 at risk EG00169 events54 affected406 at risk
Accidental Overdose	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment		EG00021 events15 affected206 at risk EG00140 events27 affected406 at risk