Efficacy and Safety of Alirocumab in Patients With Hyperc... | NCT02584504

NCT02584504

ID	Type	Description	Link
U1111-1170-7697	Other Identifier	UTN

Status Module

Sponsor/Collaborators Module

Name	Class
Regeneron Pharmaceuticals	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Alirocumab 150 mg Q4W	Experimental	Double-blind treatment period(DBTP):participants received Alirocumab 150 mg subcutaneous injection every 4 week(Q4W) alternating with placebo(for alirocumab)Q4W added to lowest-strength statin therapy(atorvastatin 5 mg daily),stable non-statin LMT/diet therapy alone for 12weeks. Participants completed DBTP,entered open-label treatment period(OLTP),received alirocumab 150 mg Q4W up to additional 52 weeks. Alirocumab dose up-titrated to 150 mg every 2 weeks(Q2W) at Week 24(OLTP:Week 12),when targeted LDL-C level at Week 20 not achieved as Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012:1) ≥100 mg/dL(2.59 mmol/L) in heterozygous familial hypercholesterolemia (heFH) participants/non-familial hypercholesterolemia (non-FH)participants with history of documented coronary heart disease;2) ≥120 mg/dL(3.10 mmol/L)in non-FH participants with history of documented diseases/other risk factors as categorized in primary prevention category III)	Drug: Alirocumab Drug: Placebo Drug: Atorvastatin Drug: Non-statin Lipid-Modifying Therapy Other: Diet Alone
Alirocumab 150 mg Q2W	Experimental	In DBTP, participants received Alirocumab 150 mg subcutaneous (SC) injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg daily), stable non-statin LMT or diet therapy alone for 12 weeks. Participants who completed DBTP were entered in OLTP and received alirocumab 150 mg Q4W up to additional 52 weeks. Alirocumab dose up-titrated to 150 mg Q2W at Week 24 (Week 12 of OLTP), when targeted LDL-C levels at Week 20 were not achieved i.e. LDL-C ≥100 mg/dL (2.59 mmol/L) or ≥120 mg/dL (3.10 mmol/L) according to Japan Atherosclerosis Society(JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.	Drug: Alirocumab Drug: Atorvastatin Drug: Non-statin Lipid-Modifying Therapy Other: Diet Alone
Placebo Q2W

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Alirocumab	Drug	Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector.	Alirocumab 150 mg Q2W

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percent Change From Baseline in Calculated LDL-C at Week 12- Intent to Treat (ITT) Analysis	Adjusted Least-squares (LS) means and standard errors at Week 12 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 12 regardless of status on- or off-treatment were used in the model (ITT analysis).	From Baseline to Week 12

Secondary Outcomes

Measure	Description	Time Frame
Percent Change From Baseline in Calculated LDL-C at Week 12- On-Treatment Analysis	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 12 (i.e. up to 21 days after last double-blind injection).	From Baseline to Week 12

Measure	Description	Time Frame
Percent Change From Baseline in Calculated LDL-C at Week 20, 24, 36, 48 and 64 -OLTP Analysis		Baseline, Weeks 20, 24, 36, 48 and 64

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Clinical Sciences & Operations	Sanofi	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Investigational Site Number 392028		Ageo-Shi			Japan
Investigational Site Number 392007

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
28623954	Background	Teramoto T, Kondo A, Kiyosue A, Harada-Shiba M, Ishigaki Y, Tobita K, Kawabata Y, Ozaki A, Baccara-Dinet MT, Sata M. Efficacy and safety of alirocumab in patients with hypercholesterolemia not adequately controlled with non-statin lipid-lowering therapy or the lowest strength of statin: ODYSSEY NIPPON study design and rationale. Lipids Health Dis. 2017 Jun 17;16(1):121. doi: 10.1186/s12944-017-0513-7.
30509509

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Alirocumab 150 mg Q4W	In double-blind treatment period (DBTP), participants received Alirocumab 150 mg subcutaneous (SC) injection every 4 weeks (Q4W) alternating with placebo (for alirocumab) Q4W added to lowest-strength statin therapy (atorvastatin 5 mg daily), stable non-statin Lipid-Modifying Therapy (LMT) or diet therapy alone for 12 weeks. Participants who completed DBTP, entered in open-label treatment period (OLTP) and received alirocumab 150 mg Q4W up to additional 52 weeks (up to Week 64). Alirocumab dose up-titrated to 150 mg every 2 weeks (Q2W) at Week 24 (Week 12 of OLTP), when LDL-C levels ≥100 mg/dL (2.59 mmol/L) or ≥120 mg/dL (3.10 mmol/L) at Week 20 according to Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Apr 26, 2017	Apr 3, 2018

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Alirocumab 150 mg Q4W

FG00054 subjectsRandomized

FG00153 subjectsRandomized

FG00256 subjectsRandomized

Baseline population included all randomized participants.

Arm/Group Information

ID	Title	Description
BG000	Alirocumab 150 mg Q4W	In DBTP, participants received Alirocumab 150 mg SC injection Q4W alternating with placebo (for alirocumab) Q4W added to lowest-strength of statin therapy (atorvastatin 5 mg daily), stable non-statin LMT or diet therapy alone for 12 weeks. Participants who completed DBTP were entered in OLTP and received alirocumab 150 mg Q4W up to additional 52 weeks (up to Week 64). Alirocumab dose up-titrated to 150 mg Q2W at Week 24 (Week 12 of OLTP), when LDL-C levels ≥100 mg/dL (2.59 mmol/L) or ≥120 mg/dL (3.10 mmol/L) at Week 20 according to Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
BG001	Alirocumab 150 mg Q2W	In DBTP, participants received Alirocumab 150 mg SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks. Participants who completed DBTP were entered in OLTP and received alirocumab 150 mg Q4W up to additional 52 weeks (up to Week 64). Alirocumab dose up-titrated to 150 mg Q2W at Week 24 (Week 12 of OLTP), when LDL-C levels ≥100 mg/dL (2.59 mmol/L) or ≥120 mg/dL (3.10 mmol/L) at Week 20 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
BG002	Placebo Q2W	In DBTP, participants received Placebo (for alirocumab) SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks. Participants who completed DBTP were entered in OLTP and received alirocumab 150 mg Q4W up to additional 52 weeks (up to Week 64). Alirocumab dose up-titrated to 150 mg Q2W at Week 24 (Week 12 of OLTP), when LDL-C levels ≥100 mg/dL (2.59 mmol/L) or ≥120 mg/dL (3.10 mmol/L) at Week 20 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00062.6± 9.8 BG00163.6± 10.4 BG00264.6± 10.0 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00021 BG00120 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Asian

Title	Measurements
	BG00054 BG00153 BG002

Calculated LDL-C in mg/dL

Calculated LDL-C in mg/dL from Friedewald formula (LDL cholesterol = Total cholesterol - high density lipoprotein [HDL] cholesterol - [Triglyceride/5]).

Mean

Standard Deviation

mg/dL

Title

Denominators

Categories

Title	Measurements
	BG000154.2± 59.5 BG001

Calculated LDL-C in mmol/L

Mean

Standard Deviation

mmol/L

Title

Denominators

Categories

Title	Measurements
	BG0003.993± 1.541 BG0013.865± 0.806 BG002

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 LDL-C at Week 12- Intent to Treat (ITT) Analysis

Adjusted Least-squares (LS) means and standard errors at Week 12 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 12 regardless of status on- or off-treatment were used in the model (ITT analysis).

ITT population: 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 12

ID	Title	Description
OG000	Alirocumab 150 mg Q4W	Participants received Alirocumab 150 mg SC injection Q4W alternating with placebo (for alirocumab) Q4W added to lowest-strength of statin therapy (atorvastatin 5 mg daily), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG001	Alirocumab 150 mg Q2W	Participants received Alirocumab 150 mg SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG002	Placebo Q2W	Participants received Placebo (for alirocumab) SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.

Units	Counts
Participants	OG00054 OG00153 OG00256

Title

Denominators

Categories

Title	Measurements
	OG000-43.8± 2.2 OG001-70.1± 2.3 OG002-4.3± 2.2

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 OG002	Alirocumab 150 mg Q4W group was compared to placebo group using an appropriate contrast statement.	Mixed Models Analysis	Threshold for significance at 0.025 level.	<0.0001	Threshold for significance at 0.025 level for Bonferroni adjustment.	Least Square (LS) Mean Difference	-39.5			2-Sided	97.5	-46.5	-32.4			Alirocumab 150 mg Q4W vs. Placebo		Superiority

Secondary

Percent Change From Baseline in Calculated LDL-C at Week 12- On-Treatment Analysis

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 12 (i.e. up to 21 days after last double-blind injection).

Modified ITT (mITT) population: 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 12

ID	Title	Description
OG000	Alirocumab 150 mg Q4W	Participants received Alirocumab 150 mg SC injection Q4W alternating with placebo (for alirocumab) Q4W added to lowest-strength of statin therapy (atorvastatin 5 mg daily), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG001	Alirocumab 150 mg Q2W	Participants received Alirocumab 150 mg SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG002	Placebo Q2W	Participants received Placebo (for alirocumab) SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.

Secondary

Percent Change From Baseline in Calculated LDL-C to Averaged Week 10 to 12: ITT Analysis

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment and assigning a weight of 0.5 for Week 10 and 12 time points.

ITT population.

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 12

ID	Title	Description
OG000	Alirocumab 150 mg Q4W	Participants received Alirocumab 150 mg SC injection Q4W alternating with placebo (for alirocumab) Q4W added to lowest-strength of statin therapy (atorvastatin 5 mg daily), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG001	Alirocumab 150 mg Q2W	Participants received Alirocumab 150 mg SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG002	Placebo Q2W	Participants received Placebo (for alirocumab) SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.

Secondary

Percent Change From Baseline in Calculated LDL-C to Averaged Week 10 to 12- On-Treatment Analysis

mITT population.

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 12

ID	Title	Description
OG000	Alirocumab 150 mg Q4W	Participants received Alirocumab 150 mg SC injection Q4W alternating with placebo (for alirocumab) Q4W added to lowest-strength of statin therapy (atorvastatin 5 mg daily), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG001	Alirocumab 150 mg Q2W	Participants received Alirocumab 150 mg SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG002	Placebo Q2W	Participants received Placebo (for alirocumab) SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.

Secondary

Percent Change From Baseline in Apolipoprotein B (Apo-B) at Week 12: ITT Analysis

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 12 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 12

ID	Title	Description
OG000	Alirocumab 150 mg Q4W	Participants received Alirocumab 150 mg SC injection Q4W alternating with placebo (for alirocumab) Q4W added to lowest-strength of statin therapy (atorvastatin 5 mg daily), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG001	Alirocumab 150 mg Q2W	Participants received Alirocumab 150 mg SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG002	Placebo Q2W	Participants received Placebo (for alirocumab) SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.

Secondary

Percent Change From Baseline in Apo-B at Week 12- On-Treatment Analysis

Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including available post-baseline on-treatment data at from Week 4 to Week 12 (i.e. up to 21 days after last double-blind injection).

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 12

ID	Title	Description
OG000	Alirocumab 150 mg Q4W	Participants received Alirocumab 150 mg SC injection Q4W alternating with placebo (for alirocumab) Q4W added to lowest-strength of statin therapy (atorvastatin 5 mg daily), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG001	Alirocumab 150 mg Q2W	Participants received Alirocumab 150 mg SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG002	Placebo Q2W	Participants received Placebo (for alirocumab) SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.

Secondary

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

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 12 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 12

ID	Title	Description
OG000	Alirocumab 150 mg Q4W	Participants received Alirocumab 150 mg SC injection Q4W alternating with placebo (for alirocumab) Q4W added to lowest-strength of statin therapy (atorvastatin 5 mg daily), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG001	Alirocumab 150 mg Q2W	Participants received Alirocumab 150 mg SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG002	Placebo Q2W	Participants received Placebo (for alirocumab) SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.

Secondary

Percent Change From Baseline in Non-HDL-C at Week 12- 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 12

ID	Title	Description
OG000	Alirocumab 150 mg Q4W	Participants received Alirocumab 150 mg SC injection Q4W alternating with placebo (for alirocumab) Q4W added to lowest-strength of statin therapy (atorvastatin 5 mg daily), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG001	Alirocumab 150 mg Q2W	Participants received Alirocumab 150 mg SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG002	Placebo Q2W	Participants received Placebo (for alirocumab) SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.

Secondary

Percent Change From Baseline in Total Cholesterol (Total-C) at Week 12- ITT Analysis

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

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

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 12

ID	Title	Description
OG000	Alirocumab 150 mg Q4W	Participants received Alirocumab 150 mg SC injection Q4W alternating with placebo (for alirocumab) Q4W added to lowest-strength of statin therapy (atorvastatin 5 mg daily), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG001	Alirocumab 150 mg Q2W	Participants received Alirocumab 150 mg SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG002	Placebo Q2W	Participants received Placebo (for alirocumab) SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.

Secondary

Percentage of Participants Reaching Calculated LDL-C Goal at Week 12- ITT Analysis

Calculated LDL-C goal was defined as calculated LDL-C <100 mg/dL (2.59 mmol/L) for heterozygous familiar hypercholesterolemia (heFH) participants or non-familial hypercholesterolemia (non-FH) participants who had a history of documented CHD, or <120 mg/dL (3.10 mmol/L) for non-FH participants who had a history of documented diseases or other risk factors as defined in JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012. Adjusted percentages at Week 12 were obtained from multiple imputation approach for handling of missing data. All available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment were included in the imputation model.

ITT population.

Posted

Number

percentage of participants

Up to Week 12

ID	Title	Description
OG000	Alirocumab 150 mg Q4W	Participants received Alirocumab 150 mg SC injection Q4W alternating with placebo (for alirocumab) Q4W added to lowest-strength of statin therapy (atorvastatin 5 mg daily), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG001	Alirocumab 150 mg Q2W	Participants received Alirocumab 150 mg SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.

Secondary

Percentage of Participants Reaching Calculated LDL-C Goal at Week 12- On-Treatment Analysis

Calculated LDL-C goal was defined as calculated LDL-C <100 mg/dL (2.59 mmol/L) for heFH participants or non-FH participants who had a history of documented CHD, or <120 mg/dL (3.10 mmol/L) for non-FH participants who had a history of documented diseases or other risk factors as defined in JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012. Adjusted percentages at Week 12 from multiple imputation approach including available post-baseline on-treatment data from Week 4 to Week 12 (i.e. up to 21 days after last double-blind injection).

mITT population.

Posted

Number

percentage of participants

Up to Week 12

ID	Title	Description
OG000	Alirocumab 150 mg Q4W	Participants received Alirocumab 150 mg SC injection Q4W alternating with placebo (for alirocumab) Q4W added to lowest-strength of statin therapy (atorvastatin 5 mg daily), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG001	Alirocumab 150 mg Q2W	Participants received Alirocumab 150 mg SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG002	Placebo Q2W

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 for handling of missing data. All available post-baseline data from Week 4 to Week 12 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 12

ID	Title	Description
OG000	Alirocumab 150 mg Q4W	Participants received Alirocumab 150 mg SC injection Q4W alternating with placebo (for alirocumab) Q4W added to lowest-strength of statin therapy (atorvastatin 5 mg daily), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG001	Alirocumab 150 mg Q2W	Participants received Alirocumab 150 mg SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG002	Placebo Q2W	Participants received Placebo (for alirocumab) SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.

Secondary

Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12- ITT Analysis

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 12 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 12

ID	Title	Description
OG000	Alirocumab 150 mg Q4W	Participants received Alirocumab 150 mg SC injection Q4W alternating with placebo (for alirocumab) Q4W added to lowest-strength of statin therapy (atorvastatin 5 mg daily), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG001	Alirocumab 150 mg Q2W	Participants received Alirocumab 150 mg SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG002	Placebo Q2W	Participants received Placebo (for alirocumab) SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.

Secondary

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

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

ITT population.

Posted

Mean

Standard Error

percent change

From Baseline to Week 12

ID	Title	Description
OG000	Alirocumab 150 mg Q4W	Participants received Alirocumab 150 mg SC injection Q4W alternating with placebo (for alirocumab) Q4W added to lowest-strength of statin therapy (atorvastatin 5 mg daily), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG001	Alirocumab 150 mg Q2W	Participants received Alirocumab 150 mg SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG002	Placebo Q2W	Participants received Placebo (for alirocumab) SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.

Secondary

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

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

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

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 12

ID	Title	Description
OG000	Alirocumab 150 mg Q4W	Participants received Alirocumab 150 mg SC injection Q4W alternating with placebo (for alirocumab) Q4W added to lowest-strength of statin therapy (atorvastatin 5 mg daily), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG001	Alirocumab 150 mg Q2W	Participants received Alirocumab 150 mg SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.
OG002	Placebo Q2W	Participants received Placebo (for alirocumab) SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks in DBTP.

Other Pre-specified

Percent Change From Baseline in Calculated LDL-C at Week 20, 24, 36, 48 and 64 -OLTP Analysis

Open-label treatment (OLT) population included all randomized participants who received at least one dose or part of dose of open-label investigational medicinal product. Here, "number analyzed" signifies participants with available data at each specified time-point.

Posted

Mean

Standard Deviation

Percent change

Baseline, Weeks 20, 24, 36, 48 and 64

ID	Title	Description
OG000	Alirocumab 150mgQ4W/Up Q2W(After Alirocumab 150mgQ4W in DBTP)	Participants who received alirocumab 150 mg Q4W during DBTP and completed DBTP, entered in OLTP and received alirocumab 150 mg Q4W from Week 12 up to Week 64. Alirocumab dose up-titrated to 150 mg Q2W at Week 24 (Week 12 of OLTP), when LDL-C levels ≥100 mg/dL (2.59 mmol/L) or ≥120 mg/dL (3.10 mmol/L) at Week 20 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
OG001	Alirocumab 150mgQ4W/Up Q2W(After Alirocumab 150mgQ2W in DBTP)	Participants who received alirocumab 150 mg Q2W during DBTP and completed DBTP, entered in OLTP and received alirocumab 150 mg Q4W from Week 12 up to Week 64. Alirocumab dose up-titrated to 150 mg Q2W at Week 24 (Week 12 of OLTP), when LDL-C levels ≥100 mg/dL (2.59 mmol/L) or ≥120 mg/dL (3.10 mmol/L) at Week 20 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Double-blind Treatment Period: Placebo Q2W	Participants received Placebo (for alirocumab) SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks.	0	56	1	56	14	56
EG001	Double-blind Treatment Period: Alirocumab 150 mg Q4W	Participants received Alirocumab 150 mg SC injection Q4W alternating with placebo (for alirocumab) Q4W added to lowest-strength of statin therapy (atorvastatin 5 mg daily) stable non-statin LMT or diet therapy alone for 12 weeks.	0	54	1	54	11	54
EG002	Double-blind Treatment Period: Alirocumab 150 mg Q2W	Participants received Alirocumab 150 mg SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks.	1	53	2	53	13	53
EG003	Open-label Treatment Period: Alirocumab 150 mg Q4W/Up Q2W	All participants received alirocumab 150 mg Q4W from the start of the open-label treatment period. Alirocumab dose up-titrated from 150 mg Q4W to 150 mg Q2W at Week 24 (Week 12 of OLTP), when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 20 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.	0	158	12	158	72	158

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDra 20.0	Systematic Assessment	EG0000 affected56 at risk EG0010 affected54 at risk EG0020 affected53 at risk EG0031 affected158 at risk
Metastases to stomach	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDra 20.0	Systematic Assessment	EG0000 affected56 at risk EG0010 affected54 at risk EG0021 affected53 at risk EG003
Non-small cell lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDra 20.0	Systematic Assessment	EG0000 affected56 at risk EG0010 affected54 at risk EG0021 affected53 at risk EG003
Pituitary tumour benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDra 20.0	Systematic Assessment	EG0000 affected56 at risk EG0010 affected54 at risk EG0020 affected53 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDra 20.0	Systematic Assessment	EG0000 affected56 at risk EG0010 affected54 at risk EG0021 affected53 at risk EG003
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDra 20.0	Systematic Assessment	EG0000 affected56 at risk EG0010 affected54 at risk EG0020 affected53 at risk EG003
Schizophrenia	Psychiatric disorders	MedDra 20.0	Systematic Assessment	EG0000 affected56 at risk EG0010 affected54 at risk EG0020 affected53 at risk EG003
Dizziness postural	Nervous system disorders	MedDra 20.0	Systematic Assessment	EG0000 affected56 at risk EG0010 affected54 at risk EG0021 affected53 at risk EG003
Facial spasm	Nervous system disorders	MedDra 20.0	Systematic Assessment	EG0000 affected56 at risk EG0010 affected54 at risk EG0020 affected53 at risk EG003
Loss of consciousness	Nervous system disorders	MedDra 20.0	Systematic Assessment	EG0000 affected56 at risk EG0010 affected54 at risk EG0021 affected53 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDra 20.0	Systematic Assessment	EG0000 affected56 at risk EG0010 affected54 at risk EG0020 affected53 at risk EG003
Angina unstable	Cardiac disorders	MedDra 20.0	Systematic Assessment	EG0001 affected56 at risk EG0010 affected54 at risk EG0020 affected53 at risk EG003
Coronary artery stenosis	Cardiac disorders	MedDra 20.0	Systematic Assessment	EG0000 affected56 at risk EG0010 affected54 at risk EG0020 affected53 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDra 20.0	Systematic Assessment	EG0000 affected56 at risk EG0010 affected54 at risk EG0020 affected53 at risk EG003
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDra 20.0	Systematic Assessment	EG0000 affected56 at risk EG0011 affected54 at risk EG0020 affected53 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDra 20.0	Systematic Assessment	EG0000 affected56 at risk EG0010 affected54 at risk EG0020 affected53 at risk EG003
Multiple fractures	Injury, poisoning and procedural complications	MedDra 20.0	Systematic Assessment	EG0000 affected56 at risk EG0010 affected54 at risk EG0020 affected53 at risk EG003
Subdural haematoma	Injury, poisoning and procedural complications	MedDra 20.0	Systematic Assessment	EG0000 affected56 at risk EG0010 affected54 at risk EG0020 affected53 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pharyngitis	Infections and infestations	MedDra 20.0	Systematic Assessment	EG0000 affected56 at risk EG0013 affected54 at risk EG0020 affected53 at risk EG0035 affected158 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDra 20.0	Systematic Assessment	EG0009 affected56 at risk EG0018 affected54 at risk EG0028 affected53 at risk EG003
Dizziness	Nervous system disorders	MedDra 20.0	Systematic Assessment	EG0003 affected56 at risk EG0010 affected54 at risk EG0020 affected53 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDra 20.0	Systematic Assessment	EG0000 affected56 at risk EG0010 affected54 at risk EG0021 affected53 at risk EG003
Non-cardiac chest pain	General disorders	MedDra 20.0	Systematic Assessment	EG0001 affected56 at risk EG0010 affected54 at risk EG0024 affected53 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDra 20.0	Systematic Assessment	EG0003 affected56 at risk EG0010 affected54 at risk EG0021 affected53 at risk EG003

ID	Term
D006937	Hypercholesterolemia

ID	Term
C571059	alirocumab
D000069059	Atorvastatin
D004032	Diet

Ancestor Terms

ID	Term
D011758	Pyrroles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D006538	Heptanoic Acids
D005227	Fatty Acids
D008055	Lipids
D009747	Nutritional Physiological Phenomena
D000066888	Diet, Food, and Nutrition
D010829	Physiological Phenomena

Units	Counts
Participants	OG00054 OG00153 OG00256

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