Trial Outcomes & Findings for Study of Alirocumab (REGN727/SAR236553) in Patients With Primary Hypercholesterolemia and Moderate, High, or Very High Cardiovascular (CV) Risk, Who Are Intolerant to Statins (ODYSSEY ALTERNATIVE) (NCT NCT01709513)

Results Overview

Calculated LDL-C values were obtained from Friedewald formula. Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

314 participants

Primary outcome timeframe

From Baseline to Week 24

Results posted on

2020-06-23

Participant Flow

The study was conducted at 67 sites in 8 countries. Overall, 519 participants were screened between 28 September 2012 and 11 August 2013, 158 of whom were screen failures. Screen failures were mainly due to exclusion criteria met. After screening, 361 participants entered into a 4-week single blind placebo run-in period.

At the end of the single blind placebo run-in period, eligible participants were randomized to treatment arms centrally using a 2:2:1 (alirocumab:ezetimibe:atorvastatin) ratio. Randomization was stratified according to prior history of myocardial infarction or ischemic stroke. 314 participants were randomized.

Participant milestones

Participant milestones
Measure	Atorvastatin (Statin Rechallenge Arm) Atorvastatin 20 mg over-encapsulated tablets orally once daily (QD) for 24 weeks and placebo (for alirocumab) subcutaneous (SC) injection every two weeks (Q2W) for 24 weeks added to stable LMT.	Ezetimibe (Active Comparator) Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Overall Study STARTED	63	125	126
Overall Study Treated	63	124	126
Overall Study COMPLETED	42	82	96
Overall Study NOT COMPLETED	21	43	30

Reasons for withdrawal

Reasons for withdrawal
Measure	Atorvastatin (Statin Rechallenge Arm) Atorvastatin 20 mg over-encapsulated tablets orally once daily (QD) for 24 weeks and placebo (for alirocumab) subcutaneous (SC) injection every two weeks (Q2W) for 24 weeks added to stable LMT.	Ezetimibe (Active Comparator) Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Overall Study Randomized but not treated	0	1	0
Overall Study Adverse Event	16	31	23
Overall Study Poor compliance to protocol	2	0	0
Overall Study Other	3	11	7

Baseline Characteristics

Study of Alirocumab (REGN727/SAR236553) in Patients With Primary Hypercholesterolemia and Moderate, High, or Very High Cardiovascular (CV) Risk, Who Are Intolerant to Statins (ODYSSEY ALTERNATIVE)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Atorvastatin (Statin Rechallenge Arm) n=63 Participants Atorvastatin 20 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable lipid-modifying therapy (LMT).	Ezetimibe (Active Comparator) n=125 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=126 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Total n=314 Participants Total of all reporting groups
Age, Continuous	63.4 years STANDARD_DEVIATION 9.5 • n=5 Participants	62.8 years STANDARD_DEVIATION 10.1 • n=7 Participants	64.1 years STANDARD_DEVIATION 9.0 • n=5 Participants	63.4 years STANDARD_DEVIATION 9.5 • n=4 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	58 Participants n=7 Participants	56 Participants n=5 Participants	142 Participants n=4 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	67 Participants n=7 Participants	70 Participants n=5 Participants	172 Participants n=4 Participants
Low Density Lipoprotein Cholesterol (LDL-C) in mg/dL	187.3 mg/dL STANDARD_DEVIATION 59.5 • n=5 Participants	193.5 mg/dL STANDARD_DEVIATION 70.9 • n=7 Participants	191.1 mg/dL STANDARD_DEVIATION 72.7 • n=5 Participants	191.3 mg/dL STANDARD_DEVIATION 69.3 • n=4 Participants
LDL-C in mmol/L	4.85 mmol/L STANDARD_DEVIATION 1.54 • n=5 Participants	5.011 mmol/L STANDARD_DEVIATION 1.837 • n=7 Participants	4.951 mmol/L STANDARD_DEVIATION 1.883 • n=5 Participants	4.954 mmol/L STANDARD_DEVIATION 1.796 • n=4 Participants

PRIMARY outcome

Timeframe: From Baseline to Week 24

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

Calculated LDL-C values were obtained from Friedewald formula. Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).

Outcome measures

Outcome measures
Measure	Ezetimibe n=122 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=126 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent--To-Treat (ITT) Analysis	-14.6 percent change Standard Error 2.2	-45.0 percent change Standard Error 2.2	—

SECONDARY outcome

Timeframe: From Baseline to Week 24

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

Calculated LDL-C values were obtained from Friedewald formula. 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 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 n=118 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=123 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percent Change From Baseline in Calculated LDL-C at Week 24 - On--Treatment Analysis	-17.1 percent change Standard Error 2.0	-52.2 percent change Standard Error 2.0	—

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: ITT population.

Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 12 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 n=122 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=126 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percent Change From Baseline in Calculated LDL--C at Week 12 -- ITT Analysis	-15.6 percent change Standard Error 2.0	-47.0 percent change Standard Error 1.9	—

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: mITT population.

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

Outcome measures

Outcome measures
Measure	Ezetimibe n=118 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=123 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percent Change From Baseline in Calculated LDL-C at Week 12 - On--Treatment Analysis	-18.0 percent change Standard Error 1.8	-51.2 percent change Standard Error 1.7	—

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline Apo B value on- or off-treatment.

Adjusted LS means and standard errors at Week 24 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 n=116 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=122 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 -- ITT Analysis	-11.2 percent change Standard Error 1.7	-36.3 percent change Standard Error 1.7	—

SECONDARY outcome

Timeframe: From Baseline to Week 24

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

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 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first).

Outcome measures

Outcome measures
Measure	Ezetimibe n=95 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=109 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percent Change From Baseline in Apo B at Week 24 -- On--Treatment Analysis	-14.4 percent change Standard Error 1.4	-42.6 percent change Standard Error 1.3	—

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline non-HDL-C value on- or off-treatment.

Adjusted LS means and standard errors at Week 24 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 n=122 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=126 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percent Change From Baseline in Non--High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 -- ITT Analysis	-14.6 percent change Standard Error 1.7	-40.2 percent change Standard Error 1.7	—

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Participants analyzed: participants of the mITT population with one baseline and at least one post-baseline Non-HDL-C value on-treatment.

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 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first).

Outcome measures

Outcome measures
Measure	Ezetimibe n=118 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=123 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percent Change From Baseline in Non--HDL-C at Week 24 -- On--Treatment Analysis	-17.1 percent change Standard Error 1.5	-46.9 percent change Standard Error 1.4	—

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline total-C value on- or off-treatment.

Adjusted LS means and standard errors at Week 24 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 n=122 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=126 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percent Change From Baseline in Total Cholesterol (Total--C) at Week 24 - ITT Analysis	-10.9 percent change Standard Error 1.4	-31.8 percent change Standard Error 1.4	—

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: Apo B ITT population.

Adjusted LS means and standard errors at Week 12 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 n=116 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=122 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percent Change From Baseline in Apo B at Week 12 -- ITT Analysis	-11.6 percent change Standard Error 1.5	-36.1 percent change Standard Error 1.5	—

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: Non-HDL-C ITT population.

Adjusted LS means and standard errors at Week 12 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 n=122 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=126 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis	-15.8 percent change Standard Error 1.5	-41.5 percent change Standard Error 1.5	—

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: Total-C ITT population.

Adjusted LS means and standard errors at Week 12 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 n=122 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=126 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percent Change From Baseline in Total-C at Week 12 - ITT Analysis	-11.6 percent change Standard Error 1.2	-32.7 percent change Standard Error 1.2	—

SECONDARY outcome

Timeframe: Up to Week 24

Population: ITT population.

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

Outcome measures

Outcome measures
Measure	Ezetimibe n=122 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=126 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis	4.4 percentage of participants	41.9 percentage of participants	—

SECONDARY outcome

Timeframe: Up to Week 24

Population: mITT population.

Adjusted percentages at Week 24 were obtained from a multiple imputation approach model including 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 n=118 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=123 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis	5.6 percentage of participants	51.2 percentage of participants	—

SECONDARY outcome

Timeframe: Up to Week 24

Population: ITT population.

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

Outcome measures

Outcome measures
Measure	Ezetimibe n=122 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=126 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis	0.8 percentage of participants	32.5 percentage of participants	—

SECONDARY outcome

Timeframe: Up to Week 24

Population: mITT population.

Adjusted percentages at Week 24 were obtained from a multiple imputation approach model including 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 n=118 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=123 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis	0.8 percentage of participants	39.0 percentage of participants	—

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Participants analyzed: participants of the ITT population.

Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression 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 n=122 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=126 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis	-7.3 percent change Standard Error 2.5	-25.9 percent change Standard Error 2.4	—

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline HDL-C value on- or off-treatment.

Adjusted LS means and standard errors at Week 24 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 n=122 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=126 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis	6.8 percent change Standard Error 1.7	7.7 percent change Standard Error 1.7	—

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Participants analyzed: participants of the ITT population

Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression 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 n=122 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=126 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis	-3.6 percent change Standard Error 2.8	-9.3 percent change Standard Error 2.7	—

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline Apo A-1 value on- or off-treatment.

Adjusted LS means and standard errors at Week 24 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 n=116 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=122 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis	2.9 percent change Standard Error 1.2	4.8 percent change Standard Error 1.2	—

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: Lipoprotein(a) ITT population.

Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression 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 n=122 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=126 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percent Change From Baseline in Lipoprotein(a) at Week 12 -- ITT Analysis	-4.5 percent change Standard Error 2.3	-21.7 percent change Standard Error 2.2	—

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: HDL-C ITT population.

Least-squares (LS) means and standard errors (SE) taken from MMRM (mixed-effect model with repeated measures) analysis

Outcome measures

Outcome measures
Measure	Ezetimibe n=122 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=126 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percent Change in HDL-C From Baseline to Week 12 -- ITT Analysis	7.6 percent change Standard Error 1.2	9.0 percent change Standard Error 1.2	—

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: Fasting Triglycerides ITT population.

Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression 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 n=122 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=126 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percent Change in Fasting Triglycerides From Baseline to Week 12 -- ITT Analysis	-9.4 percent change Standard Error 2.6	-8.0 percent change Standard Error 2.5	—

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: Apo A-1 ITT population.

Least squares (LS) means and standard errors (SE) taken from MMRM (mixed effect model with repeated measures) analysis.

Outcome measures

Outcome measures
Measure	Ezetimibe n=116 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=122 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percent Change From Baseline in Apo A--1 at Week 12 -- ITT Analysis	3.9 percent change Standard Error 1.0	5.5 percent change Standard Error 1.0	—

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline up to Week 24

Population: Safety population

Skeletal muscle-related adverse events were a predefined category including myalgia, muscle spasms, muscular weakness, musculoskeletal stiffness and muscle fatigue. Events that developed during treatment emergent adverse events period (the time from the first double-blindstudy treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.

Outcome measures

Outcome measures
Measure	Ezetimibe n=63 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=124 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg n=126 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percentage of Participants Who Experienced Skeletal Muscle-related Adverse Event (AE) Any skeletal muscle-related AE	46.0 Percentage of Participants	41.1 Percentage of Participants	32.5 Percentage of Participants
Percentage of Participants Who Experienced Skeletal Muscle-related Adverse Event (AE) Leading to treatment discontinuation	22.2 Percentage of Participants	20.2 Percentage of Participants	15.9 Percentage of Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline up to Week 24

Population: ITT population

Outcome measures

Outcome measures
Measure	Ezetimibe n=54 Participants Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=106 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Alirocumab 75 mg/ up to 150 mg n=112 Participants Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Percent Change From Baseline in Calculated LDL-C at Week 24 Versus Atorvastatin - Raw Data Description - Intent-To-Treat (ITT) Analysis	-31.9 percent change Standard Deviation 25.1	-15.2 percent change Standard Deviation 22.4	-47.3 percent change Standard Deviation 22.7

Adverse Events

Atorvastatin

Serious events: 7 serious events

Other events: 35 other events

Deaths: 0 deaths

Ezetimibe

Serious events: 10 serious events

Other events: 63 other events

Deaths: 0 deaths

Alirocumab 75 mg/ up to 150 mg

Serious events: 12 serious events

Other events: 57 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Atorvastatin n=63 participants at risk Atorvastatin 20 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 22 weeks added to stable LMT.	Ezetimibe n=124 participants at risk Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo for alirocumab SC injection Q2W for 22 weeks added to stable LMT.	Alirocumab 75 mg/ up to 150 mg n=126 participants at risk Alirocumab 75 mg SC injection Q2W for 22 weeks and placebo for atorvastatin/ezetimibe over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL--C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
General disorders Fatigue	7.9% 5/63 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.	3.2% 4/124 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.	4.8% 6/126 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.
Infections and infestations Nasopharyngitis	3.2% 2/63 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.	8.1% 10/124 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.	6.3% 8/126 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.
Infections and infestations Upper respiratory tract infection	3.2% 2/63 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.	4.0% 5/124 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.	5.6% 7/126 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.
Musculoskeletal and connective tissue disorders Arthralgia	7.9% 5/63 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.	7.3% 9/124 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.	4.8% 6/126 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.
Musculoskeletal and connective tissue disorders Back pain	7.9% 5/63 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.	5.6% 7/124 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.	4.0% 5/126 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.
Musculoskeletal and connective tissue disorders Muscle spasms	11.1% 7/63 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.	7.3% 9/124 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.	4.0% 5/126 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.
Musculoskeletal and connective tissue disorders Muscular weakness	6.3% 4/63 • Number of events 4 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.	1.6% 2/124 • Number of events 2 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.	0.79% 1/126 • Number of events 1 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.
Musculoskeletal and connective tissue disorders Myalgia	27.0% 17/63 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.	23.4% 29/124 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.	24.6% 31/126 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.
Nervous system disorders Headache	6.3% 4/63 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.	4.8% 6/124 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.	4.8% 6/126 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.
Nervous system disorders Paraesthesia	6.3% 4/63 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.	0.00% 0/124 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.	3.2% 4/126 • From Baseline up to the Last Double-Blind Injection Date + 70 Days Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment \[injection or capsules, whichever came first\] up to the day of the last double-blind injection + 70 days ) are reported.

Additional Information

Clinical Trial Administrator

Regeneron Pharmaceuticals, Inc

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Not less than 45 days prior to submission for publication or presentation, the Institution shall, or cause the Principal Investigator to, provide the Sponsor with a copy of the Manuscript. The Institution shall consider in good faith any comments from the Sponsor regarding the content, and shall delete Confidential Information upon written request of the Sponsor. At the Sponsor's request, the Institution shall delay publication for an additional 60 days to allow patent applications to be filed.
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