Trial Outcomes & Findings for Evaluation of Alirocumab Versus Ezetimibe on Top of Statin in Asia in High Cardiovascular Risk Patients With Hypercholesterolemia (NCT NCT02715726)

Last Updated: 2019-09-30

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

615 participants

Primary outcome timeframe

From Baseline to Week 24

Results posted on

2019-09-30

Participant Flow

The study was conducted at 61 centers in China, India and Thailand. Overall 1163 participants were screened between 27 July 2016 and 18 December 2017, of whom 548 were screen failures. Screen failures were mainly due to exclusion criteria met. A total of 615 participants were randomized in 2:1 ratio to alirocumab: ezetimibe.

Randomization was stratified according to prior history of myocardial infarction (MI) or ischemic stroke \[Yes/No\], and high-intensity statin treatment (Yes: atorvastatin 40 to 80 mg daily or rosuvastatin 20 to 40 mg daily, no: atorvastatin below 40 mg daily, rosuvastatin below 20 mg daily or simvastatin whatever the dose daily) and country.

Participant milestones

Participant milestones
Measure	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).	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 low-density lipoprotein cholesterol (LDL-C) level was \>=70 milligrams per deciliter (mg/dL) (1.81 millimoles per liter \[mmol/L\]) at Week 8.
Overall Study STARTED	208	407
Overall Study Treated	207	405
Overall Study Safety Population	206	406
Overall Study COMPLETED	190	380
Overall Study NOT COMPLETED	18	27

Reasons for withdrawal

Reasons for withdrawal
Measure	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).	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 low-density lipoprotein cholesterol (LDL-C) level was \>=70 milligrams per deciliter (mg/dL) (1.81 millimoles per liter \[mmol/L\]) at Week 8.
Overall Study Adverse Event	2	6
Overall Study Protocol Violation	1	0
Overall Study Death	2	1
Overall Study Participant moved	1	3
Overall Study Other than specified above	11	15
Overall Study Randomized but not treated	1	2

Baseline Characteristics

Evaluation of Alirocumab Versus Ezetimibe on Top of Statin in Asia in High Cardiovascular Risk Patients With Hypercholesterolemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ezetimibe 10 mg n=208 Participants 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.	Alirocumab 75 mg Q2W/up to 150 mg Q2W n=407 Participants 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.	Total n=615 Participants Total of all reporting groups
Age, Continuous	58.3 Years STANDARD_DEVIATION 11.2 • n=5 Participants	58.8 Years STANDARD_DEVIATION 10.7 • n=7 Participants	58.6 Years STANDARD_DEVIATION 10.8 • n=5 Participants
Sex: Female, Male Female	62 Participants n=5 Participants	92 Participants n=7 Participants	154 Participants n=5 Participants
Sex: Female, Male Male	146 Participants n=5 Participants	315 Participants n=7 Participants	461 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	208 Participants n=5 Participants	407 Participants n=7 Participants	615 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Calculated LDL-C in mmol/L	2.875 mmol/L STANDARD_DEVIATION 1.287 • n=5 Participants	2.862 mmol/L STANDARD_DEVIATION 1.253 • n=7 Participants	2.866 mmol/L STANDARD_DEVIATION 1.264 • n=5 Participants

PRIMARY outcome

Timeframe: From Baseline to Week 24

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

Outcome measures

Outcome measures
Measure	Ezetimibe 10 mg n=208 Participants 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.	Alirocumab 75 mg Q2W/up to 150 mg Q2W n=403 Participants 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.
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 24: Intent-to-treat (ITT) Analysis	-20.3 percent change Standard Error 2.0	-56.0 percent change Standard Error 1.5

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Ezetimibe 10 mg n=204 Participants 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.	Alirocumab 75 mg Q2W/up to 150 mg Q2W n=401 Participants 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.
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 24: On-Treatment Analysis	-21.3 percent change Standard Error 2.0	-58.7 percent change Standard Error 1.4

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: ITT population.

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.

Outcome measures

Outcome measures
Measure	Ezetimibe 10 mg n=208 Participants 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.	Alirocumab 75 mg Q2W/up to 150 mg Q2W n=403 Participants 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.
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 12: ITT Analysis	-22.2 percent change Standard Error 1.9	-57.1 percent change Standard Error 1.4

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: mITT population.

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).

Outcome measures

Outcome measures
Measure	Ezetimibe 10 mg n=204 Participants 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.	Alirocumab 75 mg Q2W/up to 150 mg Q2W n=401 Participants 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.
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 12: On-Treatment Analysis	-22.7 percent change Standard Error 1.9	-58.1 percent change Standard Error 1.4

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: 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).

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.

Outcome measures

Outcome measures
Measure	Ezetimibe 10 mg n=203 Participants 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.	Alirocumab 75 mg Q2W/up to 150 mg Q2W n=398 Participants 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.
Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24: ITT Analysis	-16.2 percent Change Standard Error 1.4	-43.5 percent Change Standard Error 1.0

SECONDARY outcome

Timeframe: From Baseline to Week 24

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

Outcome measures

Outcome measures
Measure	Ezetimibe 10 mg n=197 Participants 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.	Alirocumab 75 mg Q2W/up to 150 mg Q2W n=392 Participants 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.
Percent Change From Baseline in Apolipoprotein B at Week 24: On-Treatment Analysis	-17.4 percent Change Standard Error 1.4	-45.2 percent Change Standard Error 1.0

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: 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).

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.

Outcome measures

Outcome measures
Measure	Ezetimibe 10 mg n=208 Participants 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.	Alirocumab 75 mg Q2W/up to 150 mg Q2W n=403 Participants 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.
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24: ITT Analysis	-19.4 percent Change Standard Error 1.7	-47.0 percent Change Standard Error 1.2

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: 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).

Outcome measures

Outcome measures
Measure	Ezetimibe 10 mg n=204 Participants 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.	Alirocumab 75 mg Q2W/up to 150 mg Q2W n=401 Participants 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.
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 24: On-Treatment Analysis	-20.4 percent Change Standard Error 1.7	-49.1 percent Change Standard Error 1.2

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: 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).

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.

Outcome measures

Outcome measures
Measure	Ezetimibe 10 mg n=208 Participants 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.	Alirocumab 75 mg Q2W/up to 150 mg Q2W n=403 Participants 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.
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24: ITT Analysis	-13.8 percent Change Standard Error 1.2	-33.9 percent Change Standard Error 0.9

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: Apo B ITT population.

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.

Outcome measures

Outcome measures
Measure	Ezetimibe 10 mg n=203 Participants 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.	Alirocumab 75 mg Q2W/up to 150 mg Q2W n=398 Participants 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.
Percent Change From Baseline in Apolipoprotein B at Week 12: ITT Analysis	-16.5 percent Change Standard Error 1.4	-43.0 percent Change Standard Error 1.0

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: Non-HDL-C ITT population.

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.

Outcome measures

Outcome measures
Measure	Ezetimibe 10 mg n=208 Participants 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.	Alirocumab 75 mg Q2W/up to 150 mg Q2W n=403 Participants 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.
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 12: ITT Analysis	-20.7 percent Change Standard Error 1.6	-47.4 percent Change Standard Error 1.1

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: Total-C ITT population

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.

Outcome measures

Outcome measures
Measure	Ezetimibe 10 mg n=208 Participants 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.	Alirocumab 75 mg Q2W/up to 150 mg Q2W n=403 Participants 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.
Percent Change From Baseline in Total Cholesterol at Week 12: ITT Analysis	-14.9 percent Change Standard Error 1.2	-34.2 percent Change Standard Error 0.8

SECONDARY outcome

Timeframe: Up to Week 24

Population: ITT population.

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.

Outcome measures

Outcome measures
Measure	Ezetimibe 10 mg n=208 Participants 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.	Alirocumab 75 mg Q2W/up to 150 mg Q2W n=403 Participants 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.
Percentage of Participants Reaching Calculated Low Density Lipoprotein Cholesterol <70 mg/dL (1.81 mmol/L) at Week 24: ITT Analysis	40.5 percentage of participants	85.1 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 24

Population: mITT population.

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).

Outcome measures

Outcome measures
Measure	Ezetimibe 10 mg n=204 Participants 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.	Alirocumab 75 mg Q2W/up to 150 mg Q2W n=401 Participants 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.
Percentage of Participants Reaching Calculated Low Density Lipoprotein Cholesterol <70 mg/dL (1.81 mmol/L) at Week 24: On-Treatment Analysis	42.1 percentage of participants	87.0 percentage of participants

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: ITT population.

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.

Outcome measures

Outcome measures
Measure	Ezetimibe 10 mg n=208 Participants 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.	Alirocumab 75 mg Q2W/up to 150 mg Q2W n=403 Participants 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.
Percent Change From Baseline in Lipoprotein (a) (Lp[a]) at Week 24: ITT Analysis	3.956 percent Change Standard Error 2.095	-30.317 percent Change Standard Error 1.461

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: 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).

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.

Outcome measures

Outcome measures
Measure	Ezetimibe 10 mg n=208 Participants 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.	Alirocumab 75 mg Q2W/up to 150 mg Q2W n=403 Participants 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.
Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 24: ITT Analysis	6.5 percent change Standard Error 1.3	8.3 percent change Standard Error 0.9

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: ITT population.

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.

Outcome measures

Outcome measures
Measure	Ezetimibe 10 mg n=208 Participants 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.	Alirocumab 75 mg Q2W/up to 150 mg Q2W n=403 Participants 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.
Percent Change From Baseline in Fasting Triglycerides (TG) at Week 24: ITT Analysis	-14.409 percent change Standard Error 1.904	-14.462 percent change Standard Error 1.341

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: 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).

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.

Outcome measures

Outcome measures
Measure	Ezetimibe 10 mg n=203 Participants 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.	Alirocumab 75 mg Q2W/up to 150 mg Q2W n=398 Participants 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.
Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24: ITT Analysis	-0.2 percent change Standard Error 0.8	3.2 percent change Standard Error 0.6

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: ITT population.

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.

Outcome measures

Outcome measures
Measure	Ezetimibe 10 mg n=208 Participants 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.	Alirocumab 75 mg Q2W/up to 150 mg Q2W n=403 Participants 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.
Percent Change From Baseline in Lipoprotein (a) at Week 12: ITT Analysis	6.313 percent Change Standard Error 2.056	-30.064 percent Change Standard Error 1.449

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: HDL-C ITT population.

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.

Outcome measures

Outcome measures
Measure	Ezetimibe 10 mg n=208 Participants 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.	Alirocumab 75 mg Q2W/up to 150 mg Q2W n=403 Participants 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.
Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 12: ITT Analysis	6.1 percent change Standard Error 1.2	7.3 percent change Standard Error 0.9

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: ITT population.

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.

Outcome measures

Outcome measures
Measure	Ezetimibe 10 mg n=208 Participants 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.	Alirocumab 75 mg Q2W/up to 150 mg Q2W n=403 Participants 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.
Percent Change From Baseline in Fasting Triglycerides at Week 12: ITT Analysis	-13.585 percent change Standard Error 1.929	-9.965 percent change Standard Error 1.379

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: Apo A-1 ITT population.

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.

Outcome measures

Outcome measures
Measure	Ezetimibe 10 mg n=203 Participants 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.	Alirocumab 75 mg Q2W/up to 150 mg Q2W n=398 Participants 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.
Percent Change From Baseline in Apolipoprotein A-1 at Week 12 : ITT Analysis	1.1 percent change Standard Error 0.8	3.7 percent change Standard Error 0.6

Adverse Events

Ezetimibe 10 mg

Serious events: 23 serious events

Other events: 41 other events

Deaths: 3 deaths

Alirocumab 75 mg Q2W/up150 mg Q2W

Serious events: 41 serious events

Other events: 71 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Ezetimibe 10 mg n=206 participants at risk 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.	Alirocumab 75 mg Q2W/up150 mg Q2W n=406 participants at risk 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.
Infections and infestations Upper Respiratory Tract Infection	14.1% 29/206 • Number of events 39 • All Adverse Events (AEs) were collected from signature of the informed consent form up to 32 weeks of the study regardless of seriousness or relationship to investigational product. Reported AEs were treatment emergent AEs that developed or worsened during 'the treatment emergent period' (time from first dose of double-blind study drug intake \[capsule or injection, whichever came first\] to the day of last dose of double blind study drug injection + 70 days). Analysis was performed on safety population (participants who received at least 1 dose or partial dose of study drug \[injection or capsule)\]. Participants were analyzed according to the treatment actually received.	13.3% 54/406 • Number of events 69 • All Adverse Events (AEs) were collected from signature of the informed consent form up to 32 weeks of the study regardless of seriousness or relationship to investigational product. Reported AEs were treatment emergent AEs that developed or worsened during 'the treatment emergent period' (time from first dose of double-blind study drug intake \[capsule or injection, whichever came first\] to the day of last dose of double blind study drug injection + 70 days). Analysis was performed on safety population (participants who received at least 1 dose or partial dose of study drug \[injection or capsule)\]. Participants were analyzed according to the treatment actually received.
Injury, poisoning and procedural complications Accidental Overdose	7.3% 15/206 • Number of events 21 • All Adverse Events (AEs) were collected from signature of the informed consent form up to 32 weeks of the study regardless of seriousness or relationship to investigational product. Reported AEs were treatment emergent AEs that developed or worsened during 'the treatment emergent period' (time from first dose of double-blind study drug intake \[capsule or injection, whichever came first\] to the day of last dose of double blind study drug injection + 70 days). Analysis was performed on safety population (participants who received at least 1 dose or partial dose of study drug \[injection or capsule)\]. Participants were analyzed according to the treatment actually received.	6.7% 27/406 • Number of events 40 • All Adverse Events (AEs) were collected from signature of the informed consent form up to 32 weeks of the study regardless of seriousness or relationship to investigational product. Reported AEs were treatment emergent AEs that developed or worsened during 'the treatment emergent period' (time from first dose of double-blind study drug intake \[capsule or injection, whichever came first\] to the day of last dose of double blind study drug injection + 70 days). Analysis was performed on safety population (participants who received at least 1 dose or partial dose of study drug \[injection or capsule)\]. Participants were analyzed according to the treatment actually received.

Additional Information

Trial Transparency Team

Sanofi aventis recherche & développement

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Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
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