Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   37989   clinical trials with a EudraCT protocol, of which   6231   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of an Every Four Weeks Treatment Regimen of Alirocumab in Patients with Primary Hypercholesterolemia

    Summary
    EudraCT number
    2013-002343-29
    Trial protocol
    GB   HU   SK   BG   NO  
    Global end of trial date
    28 Apr 2015

    Results information
    Results version number
    v3(current)
    This version publication date
    02 Dec 2019
    First version publication date
    22 May 2016
    Other versions
    v1 , v2
    Version creation reason
    • Correction of full data set
    Minor corrections

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    R727-CL-1308
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01926782
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    Study Name: ODYSSEY CHOICE I
    Sponsors
    Sponsor organisation name
    Regeneron Pharmaceuticals, Inc.
    Sponsor organisation address
    777 Old Saw Mill River Rd., Tarrytown, United States, 10591
    Public contact
    Clinical Trial Management, Regeneron Pharmaceuticals, Inc., clinicaltrials@regeneron.com
    Scientific contact
    Clinical Trial Management, Regeneron Pharmaceuticals, Inc., clinicaltrials@regeneron.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    26 Jun 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Apr 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine the efficacy, long-term safety, and tolerability of alirocumab 300 mg every 4 weeks (Q4W), in comparison with placebo, as well as its potential as a starting regimen. The dose regimen of 75 mg every 2 weeks (Q2W), as used in other studies, was added as a calibrator.
    Protection of trial subjects
    This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with the International Conference on Harmonisation (ICH) guidelines for Good Clinical Practice (GCP) and applicable regulatory requirements.
    Background therapy
    The study was conducted in 2 separate populations concurrently: subjects receiving concomitant statin therapy and subjects not receiving concomitant statin therapy. Subjects receiving concomitant statin were to receive stable daily doses of rosuvastatin, atorvastatin, or simvastatin for at least 4 weeks. Background treatment with other lipid-modifying therapy (LMT) was allowed for all patients, provided they had been on a stable dose for at least 4 weeks (6 weeks for fenofibrate) prior to study entry.
    Evidence for comparator
    -
    Actual start date of recruitment
    25 Sep 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Norway: 17
    Country: Number of subjects enrolled
    Slovakia: 50
    Country: Number of subjects enrolled
    United Kingdom: 63
    Country: Number of subjects enrolled
    Bulgaria: 19
    Country: Number of subjects enrolled
    Hungary: 37
    Country: Number of subjects enrolled
    Canada: 27
    Country: Number of subjects enrolled
    Israel: 14
    Country: Number of subjects enrolled
    United States: 576
    Worldwide total number of subjects
    803
    EEA total number of subjects
    186
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    518
    From 65 to 84 years
    282
    85 years and over
    3

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    The study was conducted at 97 sites in 8 countries. A total of 1491 subjects were screened between September 2013 and April 2014, 688 of whom were screen failures. Screen failures were mainly due to inclusion criteria not met.

    Pre-assignment
    Screening details
    Randomization was stratified according to statin therapy (with/ without) and cardiovascular risk (moderate vs. high/very high) within the population receiving concomitant statin. Assignment to treatment arms was done using an Interactive Voice/Web Response System in 2:1:4 (Placebo: 75 mg: 300 mg) ratio after confirmation of selection criteria.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo Q2W with Concomitant Statin
    Arm description
    Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) with stable statin therapy for 48 weeks.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo (for Alirocumab)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo matched to alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.

    Arm title
    Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin
    Arm description
    One SC injection of each Alirocumab 75 mg and placebo Q2W with stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
    Arm type
    Experimental

    Investigational medicinal product name
    Alirocumab
    Investigational medicinal product code
    REGN727, SAR236553
    Other name
    Praluent
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.

    Investigational medicinal product name
    Placebo (for Alirocumab)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo matched to alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.

    Arm title
    Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Arm description
    Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W with stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
    Arm type
    Experimental

    Investigational medicinal product name
    Alirocumab
    Investigational medicinal product code
    REGN727, SAR236553
    Other name
    Praluent
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.

    Investigational medicinal product name
    Placebo (for Alirocumab)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo matched to alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.

    Arm title
    Placebo Q2W Without Concomitant Statin
    Arm description
    Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo (for Alirocumab)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo matched to alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.

    Arm title
    Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin
    Arm description
    One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
    Arm type
    Experimental

    Investigational medicinal product name
    Alirocumab
    Investigational medicinal product code
    REGN727, SAR236553
    Other name
    Praluent
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.

    Investigational medicinal product name
    Placebo (for Alirocumab)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo matched to alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.

    Arm title
    Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Arm description
    Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
    Arm type
    Experimental

    Investigational medicinal product name
    Alirocumab
    Investigational medicinal product code
    REGN727, SAR236553
    Other name
    Praluent
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.

    Investigational medicinal product name
    Placebo (for Alirocumab)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo matched to alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.

    Number of subjects in period 1
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Started
    157
    78
    312
    73
    37
    146
    Treated
    157
    78
    312
    72
    37
    146
    Completed 24 Weeks Treatment Period
    137
    68
    285
    58
    31
    120
    Completed
    129
    65
    272
    53
    29
    105
    Not completed
    28
    13
    40
    20
    8
    41
         Subject moved
    2
    -
    1
    1
    -
    3
         Physician decision
    -
    2
    1
    1
    -
    -
         Other than specified
    2
    3
    5
    12
    4
    11
         Adverse event
    13
    4
    17
    4
    3
    14
         Poor compliance to protocol
    5
    3
    8
    -
    1
    6
         Randomized and not treated
    -
    -
    -
    1
    -
    -
         Consent withdrawn by subject
    6
    1
    8
    1
    -
    5
         Related to IMP administration
    -
    -
    -
    -
    -
    2

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo Q2W with Concomitant Statin
    Reporting group description
    Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) with stable statin therapy for 48 weeks.

    Reporting group title
    Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin
    Reporting group description
    One SC injection of each Alirocumab 75 mg and placebo Q2W with stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.

    Reporting group title
    Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Reporting group description
    Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W with stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.

    Reporting group title
    Placebo Q2W Without Concomitant Statin
    Reporting group description
    Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.

    Reporting group title
    Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin
    Reporting group description
    One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.

    Reporting group title
    Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Reporting group description
    Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.

    Reporting group values
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin Total
    Number of subjects
    157 78 312 73 37 146 803
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    61.6 ± 9.7 60.7 ± 9.1 61.6 ± 10 59.4 ± 10.2 59.3 ± 11.3 59.2 ± 10.8 -
    Gender categorical
    Units: Subjects
        Female
    56 27 122 33 23 80 341
        Male
    101 51 190 40 14 66 462
    Calculated LDL-C in mg/dL
    Calculated LDL-C from Friedewald formula (LDL-C = Total cholesterol High density lipoprotein cholesterol [Triglyceride/5])
    Units: mg/dL
        arithmetic mean (standard deviation)
    112.1 ± 37.3 114.9 ± 36 112.4 ± 32.8 131 ± 30.4 148.4 ± 36.8 146.1 ± 33.5 -
    Calculated LDL-C in mmol/L
    Units: mmol/L
        arithmetic mean (standard deviation)
    2.903 ± 0.965 2.977 ± 0.933 2.912 ± 0.85 3.392 ± 0.787 3.842 ± 0.953 3.785 ± 0.868 -

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Placebo Q2W with Concomitant Statin
    Reporting group description
    Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) with stable statin therapy for 48 weeks.

    Reporting group title
    Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin
    Reporting group description
    One SC injection of each Alirocumab 75 mg and placebo Q2W with stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.

    Reporting group title
    Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Reporting group description
    Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W with stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.

    Reporting group title
    Placebo Q2W Without Concomitant Statin
    Reporting group description
    Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.

    Reporting group title
    Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin
    Reporting group description
    One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.

    Reporting group title
    Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Reporting group description
    Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.

    Primary: Percent Change From Baseline in Calculated LDL-C in Subjects Receiving Concomitant Statin Therapy - Intent-to-Treat (ITT Analysis)

    Close Top of page
    End point title
    Percent Change From Baseline in Calculated LDL-C in Subjects Receiving Concomitant Statin Therapy - Intent-to-Treat (ITT Analysis) [1]
    End point description
    Adjusted least squares (LS) means and standard errors at Week 24 and at averaged Week 21 to 24 were obtained from a mixed effect model with repeated measures (MMRM) model 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 this model (ITT analysis). ITT population (subjects with concomitant statin therapy): all randomized subjects who received concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment. Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
    End point type
    Primary
    End point timeframe
    From Baseline to Week 24
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is referring to only the 3 arms in which subjects were receiving concomitant statin therapy
    End point values
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Number of subjects analysed
    156
    76
    308
    Units: Percent change
    least squares mean (standard error)
        At Week 24
    -0.1 ± 2.3
    -51.6 ± 3.3
    -58.8 ± 1.6
        At averaged Week 21 to 24
    -0.8 ± 2
    -57.9 ± 2.8
    -65.8 ± 1.4
    Statistical analysis title
    Placebo v Alirocumab 300mg Q4W/150mg Q2W: At Wk 24
    Statistical analysis description
    Alirocumab 300 mg group was compared to placebo group using an appropriate contrast statement.
    Comparison groups
    Placebo Q2W with Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Number of subjects included in analysis
    464
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [2]
    Method
    Mixed models analysis
    Parameter type
    Least Square (LS) Mean Difference
    Point estimate
    -58.7
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -65
         upper limit
    -52.4
    Notes
    [2] - Threshold for significance ≤ 0.025.
    Statistical analysis title
    Placebo v Alirocumab 300mg Q4W/150mg Q2W: Wk 21-24
    Statistical analysis description
    Alirocumab 300 mg group was compared to placebo group using an appropriate contrast statement.
    Comparison groups
    Placebo Q2W with Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Number of subjects included in analysis
    464
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [3]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    -65
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -70.4
         upper limit
    -59.5
    Notes
    [3] - Threshold for significance ≤ 0.025.

    Primary: Percent Change From Baseline in Calculated LDL-C in Subjects Not Receiving Concomitant Statin Therapy – ITT Analysis

    Close Top of page
    End point title
    Percent Change From Baseline in Calculated LDL-C in Subjects Not Receiving Concomitant Statin Therapy – ITT Analysis [4]
    End point description
    Adjusted LS means and standard errors at Week 24 and at averaged Week 21 to 24 from MMRM including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. ITT population (subjects without concomitant statin therapy): all randomized subjects who did not receive concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment. Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
    End point type
    Primary
    End point timeframe
    From Baseline to Week 24
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is referring to only the 3 arms in which subjects were not receiving concomitant statin therapy
    End point values
    Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects analysed
    71
    37
    144
    Units: Percent change
    least squares mean (standard error)
        At Week 24
    -0.3 ± 2.7
    -50.2 ± 3.7
    -52.7 ± 1.9
        At averaged Week 21 to 24
    -1.6 ± 2.6
    -54 ± 3.6
    -56.9 ± 1.8
    Statistical analysis title
    Placebo v Alirocumab 300mg Q4W/150mg Q2W: At Wk 24
    Statistical analysis description
    Alirocumab 300 mg group was compared to placebo group using an appropriate contrast statement.
    Comparison groups
    Placebo Q2W Without Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [5]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    -52.4
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -59.8
         upper limit
    -45
    Notes
    [5] - Threshold for significance ≤ 0.025.
    Statistical analysis title
    Placebo v Alirocumab 300mg Q4W/150mg Q2W: Wk 21-24
    Statistical analysis description
    Alirocumab 300 mg group was compared to placebo group using an appropriate contrast statement.
    Comparison groups
    Placebo Q2W Without Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [6]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    -55.2
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -62.3
         upper limit
    -48.1
    Notes
    [6] - Threshold for significance ≤ 0.025.

    Secondary: Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis

    Close Top of page
    End point title
    Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis
    End point description
    Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection) (on-treatment analysis). Modified ITT (mITT) population (subjects with or without concomitant statin therapy): all randomized and treated subjects who did not receive concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on-treatment. Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 24
    End point values
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects analysed
    151
    75
    302
    70
    37
    141
    Units: percent change
        least squares mean (standard error)
    -0.3 ± 2.1
    -55.1 ± 3
    -62.3 ± 1.5
    -0.4 ± 2
    -54.6 ± 2.8
    -59.4 ± 1.4
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W
    Statistical analysis description
    A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 0.025 level.
    Comparison groups
    Placebo Q2W Without Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects included in analysis
    211
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [7]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    -59
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -64.6
         upper limit
    -53.4
    Notes
    [7] - Threshold for significance ≤ 0.025.
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W + Statin
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W with Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [8]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    -62
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -67.7
         upper limit
    -56.2
    Notes
    [8] - Threshold for significance ≤ 0.025.

    Secondary: Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis

    Close Top of page
    End point title
    Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
    End point description
    Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 24
    End point values
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects analysed
    156
    76
    308
    71
    37
    144
    Units: percent change
        least squares mean (standard error)
    1.1 ± 2.2
    -45.3 ± 3.1
    -55.3 ± 1.5
    0.3 ± 2.1
    -51.8 ± 2.9
    -58.4 ± 1.4
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W Without Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [9]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    -58.7
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -64.5
         upper limit
    -53
    Notes
    [9] - Threshold for significance ≤ 0.025.
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W + Statin
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W with Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Number of subjects included in analysis
    464
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [10]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    -56.3
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -62.3
         upper limit
    -50.3
    Notes
    [10] - Threshold for significance ≤ 0.025.

    Secondary: Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis

    Close Top of page
    End point title
    Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis
    End point description
    Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). mITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 24
    End point values
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects analysed
    151
    75
    302
    70
    37
    141
    Units: percent change
        least squares mean (standard error)
    1.4 ± 1.9
    -47.3 ± 2.8
    -58 ± 1.4
    -0.5 ± 2
    -53.9 ± 2.7
    -60 ± 1.4
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W Without Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects included in analysis
    211
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [11]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    -59.5
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -65
         upper limit
    -54.1
    Notes
    [11] - Threshold for significance ≤ 0.025.
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W + Statin
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W with Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [12]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    -59.4
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -64.8
         upper limit
    -54
    Notes
    [12] - Threshold for significance ≤ 0.025.

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

    Close Top of page
    End point title
    Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis
    End point description
    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. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline Apo B value on- or off-treatment (Apo B ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 24
    End point values
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects analysed
    146
    75
    292
    71
    34
    138
    Units: percent change
        least squares mean (standard error)
    3.1 ± 1.8
    -36.7 ± 2.6
    -45.1 ± 1.3
    -0.7 ± 2.3
    -39 ± 3.3
    -40.2 ± 1.6
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W Without Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects included in analysis
    209
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [13]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    -39.5
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -45.8
         upper limit
    -33.1
    Notes
    [13] - Threshold for significance ≤ 0.025.
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W + Statin
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W with Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Number of subjects included in analysis
    438
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [14]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    -48.2
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -53.2
         upper limit
    -43.2
    Notes
    [14] - Threshold for significance ≤ 0.025.

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

    Close Top of page
    End point title
    Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis
    End point description
    Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). Subjects of mITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline Apo-B value on-treatment (Apo B mITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 24
    End point values
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects analysed
    142
    74
    286
    70
    37
    141
    Units: percent change
        least squares mean (standard error)
    3.1 ± 1.7
    -38.3 ± 2.5
    -47.2 ± 1.2
    -0.3 ± 2
    -42 ± 2.7
    -44.8 ± 1.4
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W Without Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects included in analysis
    211
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [15]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    -44.5
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -49.9
         upper limit
    -39.1
    Notes
    [15] - Threshold for significance ≤ 0.025.
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W + Statin
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W with Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Number of subjects included in analysis
    428
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [16]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    -50.3
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -55
         upper limit
    -45.6
    Notes
    [16] - Threshold for significance ≤ 0.025.

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

    Close Top of page
    End point title
    Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis
    End point description
    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. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline non-HDL-C value on- or off-treatment (non-HDL-C ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 24
    End point values
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects analysed
    156
    76
    308
    71
    37
    144
    Units: percent change
        least squares mean (standard error)
    0.3 ± 1.9
    -41.6 ± 2.7
    -49.7 ± 1.3
    -0.3 ± 2.5
    -43.6 ± 3.4
    -43.3 ± 1.7
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W Without Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [17]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    -43
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -49.9
         upper limit
    -36.2
    Notes
    [17] - Threshold for significance ≤ 0.025.
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W + Statin
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W with Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Number of subjects included in analysis
    464
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [18]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    -50
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -55.3
         upper limit
    -44.8
    Notes
    [18] - Threshold for significance ≤ 0.025.

    Secondary: Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis

    Close Top of page
    End point title
    Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis
    End point description
    Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). Subjects of the mITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline non-HDL-C value on-treatment (non-HDL-C mITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 24
    End point values
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects analysed
    151
    75
    302
    70
    37
    141
    Units: percent change
        least squares mean (standard error)
    0.2 ± 1.8
    -44.4 ± 2.5
    -52.6 ± 1.2
    0.1 ± 2.1
    -47.2 ± 2.8
    -48.9 ± 1.4
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W Without Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects included in analysis
    211
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [19]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    -49
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -54.8
         upper limit
    -43.3
    Notes
    [19] - Threshold for significance ≤ 0.025.
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W + Statin
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W with Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [20]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    -52.8
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -57.6
         upper limit
    -47.9
    Notes
    [20] - Threshold for significance ≤ 0.025.

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

    Close Top of page
    End point title
    Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis
    End point description
    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. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline Total-C value on- or off-treatment (Total-C ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 24
    End point values
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects analysed
    156
    76
    308
    71
    37
    144
    Units: percent change
        least squares mean (standard error)
    -0.8 ± 1.4
    -30 ± 2
    -35.8 ± 1
    -1.9 ± 1.9
    -32.5 ± 2.6
    -33.3 ± 1.3
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W Without Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [21]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    -31.4
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -36.6
         upper limit
    -26.3
    Notes
    [21] - Threshold for significance ≤ 0.025.
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W + Statin
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W with Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Number of subjects included in analysis
    464
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [22]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    -35
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -38.9
         upper limit
    -31.1
    Notes
    [22] - Threshold for significance ≤ 0.025.

    Secondary: Percent Change From Baseline in Apo B at Week 12 - ITT Analysis

    Close Top of page
    End point title
    Percent Change From Baseline in Apo B at Week 12 - ITT Analysis
    End point description
    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. Apo B ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 24
    End point values
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects analysed
    146
    75
    292
    71
    34
    138
    Units: percent change
        least squares mean (standard error)
    3.6 ± 1.8
    -33 ± 2.5
    -41.2 ± 1.3
    -2.3 ± 1.7
    -40.8 ± 2.5
    -46.4 ± 1.3
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W Without Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects included in analysis
    209
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [23]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    -44.1
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -49
         upper limit
    -39.2
    Notes
    [23] - Threshold for significance ≤ 0.025.
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W + Statin
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W with Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Number of subjects included in analysis
    438
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [24]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    -44.8
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -49.7
         upper limit
    -39.9
    Notes
    [24] - Threshold for significance ≤ 0.025.

    Secondary: Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis

    Close Top of page
    End point title
    Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis
    End point description
    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. Non-HDL-C ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 24
    End point values
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects analysed
    156
    76
    308
    71
    37
    144
    Units: percent change
        least squares mean (standard error)
    0.6 ± 1.9
    -37.4 ± 2.7
    -46.5 ± 1.3
    -0.4 ± 1.8
    -45.8 ± 2.5
    -49.9 ± 1.3
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W Without Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [25]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    -49.5
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -54.5
         upper limit
    -44.6
    Notes
    [25] - Threshold for significance ≤ 0.025.
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W + Statin
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W with Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Number of subjects included in analysis
    464
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [26]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    -47.1
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -52.2
         upper limit
    -42
    Notes
    [26] - Threshold for significance ≤ 0.025.

    Secondary: Percent Change From Baseline in Total-C at Week 12 - ITT Analysis

    Close Top of page
    End point title
    Percent Change From Baseline in Total-C at Week 12 - ITT Analysis
    End point description
    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. Total-C ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 24
    End point values
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects analysed
    156
    76
    308
    71
    37
    144
    Units: percent change
        least squares mean (standard error)
    -0.1 ± 1.3
    -26.5 ± 1.9
    -32.9 ± 1
    -1 ± 1.4
    -33.4 ± 2
    -37.4 ± 1
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W Without Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [27]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    -36.4
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -40.4
         upper limit
    -32.4
    Notes
    [27] - Threshold for significance ≤ 0.025.
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W + Statin
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W with Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Number of subjects included in analysis
    464
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [28]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    -32.8
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -36.5
         upper limit
    -29.1
    Notes
    [28] - Threshold for significance ≤ 0.025.

    Secondary: Percentage of Very High Cardiovascular (CV) Risk Subjects Reaching Calculated LDL-C<70 mg/dL or Moderate or High CV Risk Subjects Reaching Calculated LDL-C<100 mg/dL at Week 24 - ITT Analysis

    Close Top of page
    End point title
    Percentage of Very High Cardiovascular (CV) Risk Subjects Reaching Calculated LDL-C<70 mg/dL or Moderate or High CV Risk Subjects Reaching Calculated LDL-C<100 mg/dL at Week 24 - ITT Analysis
    End point description
    Very high CV risk: history of documented coronary heart disease (CHD) or CHD risk equivalent. High CV risk: calculated 10-year fatal CVD risk score ≥5%, moderate chronic kidney disease, type 1/type 2 diabetes mellitus (DM) without target organ damage, or heFH not meeting definition of very high risk. Moderate CV risk: calculated 10-year fatal CVD risk score ≥1 &<5%. CHD risk equivalent: peripheral arterial disease, ischemic stroke, transient ischemic attack, abdominal aortic aneurysm, carotid artery(CA)occlusion>50%, carotid endarterectomy/CA stent procedure, renal artery stenosis/stent procedure, type 1/type 2 DM with target organ damage. Adjusted percentages at Week 24 obtained from 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 included in imputation model. ITT population (subjects with or without concomitant statin therapy).
    End point type
    Secondary
    End point timeframe
    Up to Week 24
    End point values
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects analysed
    156
    76
    308
    71
    37
    144
    Units: percentage of subjects
        number (not applicable)
    22.2
    82.5
    85.2
    9.4
    84.9
    78.9
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Statistical analysis used a multiple imputation approach followed by logistic regression model.
    Comparison groups
    Placebo Q2W Without Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [29]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    68
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    20.9
         upper limit
    221
    Notes
    [29] - Threshold for significance ≤ 0.025.
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W + Statin
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Statistical analysis used multiple imputation approach followed by logistic regression model.
    Comparison groups
    Placebo Q2W with Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Number of subjects included in analysis
    464
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [30]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    25.6
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    13.7
         upper limit
    47.8
    Notes
    [30] - Threshold for significance ≤ 0.025.

    Secondary: Percentage of Very High CV Risk Subjects Reaching Calculated LDL-C <70 mg/dL(1.81 mmol/L) or Moderate or High CV Risk Subjects Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis

    Close Top of page
    End point title
    Percentage of Very High CV Risk Subjects Reaching Calculated LDL-C <70 mg/dL(1.81 mmol/L) or Moderate or High CV Risk Subjects Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis
    End point description
    Adjusted percentages at Week 24 were from 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). mITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
    End point type
    Secondary
    End point timeframe
    Up to Week 24
    End point values
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects analysed
    151
    75
    302
    70
    37
    141
    Units: percentage of subjects
        number (not applicable)
    22.5
    86.4
    89.5
    11.3
    93
    88.6
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Statistical analysis used a multiple imputation approach followed by logistic regression model.
    Comparison groups
    Placebo Q2W Without Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects included in analysis
    211
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [31]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    280.2
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    56.7
         upper limit
    1385.7
    Notes
    [31] - Threshold for significance ≤ 0.025.
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W + Statin
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Statistical analysis used multiple imputation approach followed by logistic regression model.
    Comparison groups
    Placebo Q2W with Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [32]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    41.3
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    20.3
         upper limit
    83.8
    Notes
    [32] - Threshold for significance ≤ 0.025.

    Secondary: Percentage of Subjects Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis

    Close Top of page
    End point title
    Percentage of Subjects Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis
    End point description
    Adjusted percentages at Week 24 were obtained from multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
    End point type
    Secondary
    End point timeframe
    Up to Week 24
    End point values
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects analysed
    156
    76
    308
    71
    37
    144
    Units: percentage of subjects
        number (not applicable)
    10.9
    74.4
    80.4
    3.3
    57.7
    62
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Statistical analysis used a multiple imputation approach followed by logistic regression model.
    Comparison groups
    Placebo Q2W Without Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [33]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    90.6
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    16.5
         upper limit
    498.3
    Notes
    [33] - Threshold for significance ≤ 0.025.
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W + Statin
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Statistical analysis used multiple imputation approach followed by logistic regression model.
    Comparison groups
    Placebo Q2W with Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Number of subjects included in analysis
    464
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [34]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    49.5
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    23.4
         upper limit
    104.4
    Notes
    [34] - Threshold for significance ≤ 0.025.

    Secondary: Percentage of Subjects Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis

    Close Top of page
    End point title
    Percentage of Subjects Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis
    End point description
    Adjusted percentages at Week 24 from multiple imputation approach model including available post-baseline data from Week 4 to Week 24 (i.e. up to 21 days after last injection). mITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
    End point type
    Secondary
    End point timeframe
    Up to Week 24
    End point values
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects analysed
    151
    75
    302
    70
    37
    141
    Units: percentage of subjects
        number (not applicable)
    10.8
    77.4
    84.8
    2.1
    61.7
    70.4
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Statistical analysis used multiple imputation approach followed by logistic regression model.
    Comparison groups
    Placebo Q2W Without Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects included in analysis
    211
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [35]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    297.1
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    27.9
         upper limit
    3160.6
    Notes
    [35] - Threshold for significance ≤ 0.025.
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W + Statin
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Statistical analysis used a multiple imputation approach followed by logistic regression model.
    Comparison groups
    Placebo Q2W with Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [36]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    77.7
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    34.1
         upper limit
    176.8
    Notes
    [36] - Threshold for significance ≤ 0.025.

    Secondary: Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis

    Close Top of page
    End point title
    Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis
    End point description
    Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression 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 population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 24
    End point values
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects analysed
    156
    76
    308
    71
    37
    144
    Units: percent change
        arithmetic mean (standard error)
    9.8 ± 2.4
    -16.9 ± 3.3
    -19.3 ± 1.6
    6.4 ± 3.4
    -14 ± 4.8
    -21.3 ± 2.4
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Statistical analysis used a multiple imputation approach followed by a robust regression model.
    Comparison groups
    Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin v Placebo Q2W Without Concomitant Statin
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [37]
    Method
    Regression, Robust
    Parameter type
    Adjusted Mean Difference
    Point estimate
    -27.7
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -37
         upper limit
    -18.3
    Notes
    [37] - Threshold for significance ≤ 0.025.
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W + Statin
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Statistical analysis used a multiple imputation approach followed by a robust regression model.
    Comparison groups
    Placebo Q2W with Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Number of subjects included in analysis
    464
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [38]
    Method
    Regression, Robust
    Parameter type
    Adjusted Mean Difference
    Point estimate
    -29.1
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -35.5
         upper limit
    -22.7
    Notes
    [38] - Threshold for significance ≤ 0.025.

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

    Close Top of page
    End point title
    Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis
    End point description
    Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 24
    End point values
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects analysed
    156
    76
    308
    71
    37
    144
    Units: percent change
        arithmetic mean (standard error)
    7 ± 2.3
    -12.4 ± 3.2
    -19.6 ± 1.6
    -5.5 ± 3.3
    -26.9 ± 4.7
    -28.9 ± 2.3
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Statistical analysis used a multiple imputation approach followed by a robust regression model.
    Comparison groups
    Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin v Placebo Q2W Without Concomitant Statin
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [39]
    Method
    Regression, Robust
    Parameter type
    Adjusted Mean Difference
    Point estimate
    -23.5
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -32.4
         upper limit
    -14.5
    Notes
    [39] - Threshold for significance ≤ 0.025.
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W + Statin
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Statistical analysis used a multiple imputation approach followed by a robust regression model.
    Comparison groups
    Placebo Q2W with Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Number of subjects included in analysis
    464
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [40]
    Method
    Regression, Robust
    Parameter type
    Adjusted Mean Difference
    Point estimate
    -26.6
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -32.8
         upper limit
    -20.4
    Notes
    [40] - Threshold for significance ≤ 0.025.

    Secondary: Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis

    Close Top of page
    End point title
    Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis
    End point description
    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. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline HDL-C value on- or off-treatment (HDL-C ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 24
    End point values
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects analysed
    156
    76
    308
    71
    37
    144
    Units: percent change
        least squares mean (standard error)
    -1.5 ± 1.2
    6 ± 1.7
    3.6 ± 0.8
    -5.3 ± 1.7
    -0.1 ± 2.4
    2.5 ± 1.2
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W Without Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0003 [41]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    7.8
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    3.1
         upper limit
    12.6
    Notes
    [41] - Threshold for significance ≤ 0.025.
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W + Statin
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W with Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Number of subjects included in analysis
    464
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0004 [42]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    5.1
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    1.9
         upper limit
    8.4
    Notes
    [42] - Threshold for significance ≤ 0.025.

    Secondary: Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis

    Close Top of page
    End point title
    Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis
    End point description
    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. HDL-C ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 24
    End point values
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects analysed
    156
    76
    308
    71
    37
    144
    Units: percent change
        least squares mean (standard error)
    0.4 ± 1.2
    7.6 ± 1.8
    5.7 ± 0.9
    -0.9 ± 1.6
    2.5 ± 2.2
    6 ± 1.1
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W Without Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0004 [43]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    6.9
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    2.6
         upper limit
    11.1
    Notes
    [43] - Threshold for significance ≤ 0.025.
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W + Statin
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W with Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Number of subjects included in analysis
    464
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0007 [44]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    5.2
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    1.8
         upper limit
    8.7
    Notes
    [44] - Threshold for significance ≤ 0.025.

    Secondary: Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis

    Close Top of page
    End point title
    Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
    End point description
    Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 24
    End point values
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects analysed
    156
    76
    308
    71
    37
    144
    Units: percent change
        arithmetic mean (standard error)
    -0.1 ± 2.4
    -6.7 ± 3.3
    -15.2 ± 1.6
    -1.5 ± 3.4
    -9.8 ± 4.9
    -13.4 ± 2.5
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Statistical analysis used a multiple imputation approach followed by a robust regression model.
    Comparison groups
    Placebo Q2W Without Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0042 [45]
    Method
    Regression, Robust
    Parameter type
    Adjusted Mean Difference
    Point estimate
    -11.9
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -21.3
         upper limit
    -2.6
    Notes
    [45] - Threshold for significance ≤ 0.025.
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W + Statin
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Statistical analysis used multiple imputation approach followed by a robust regression model.
    Comparison groups
    Placebo Q2W with Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Number of subjects included in analysis
    464
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [46]
    Method
    Regression, Robust
    Parameter type
    Adjusted Mean Difference
    Point estimate
    -15.1
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -21.5
         upper limit
    -8.6
    Notes
    [46] - Threshold for significance ≤ 0.025.

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

    Close Top of page
    End point title
    Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis
    End point description
    Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 24
    End point values
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects analysed
    156
    76
    308
    71
    37
    144
    Units: percent change
        arithmetic mean (standard error)
    0.5 ± 2.4
    -7.3 ± 3.5
    -13.1 ± 1.7
    1.8 ± 3.2
    -18.3 ± 4.6
    -12.3 ± 2.3
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Statistical analysis used a multiple imputation approach followed by a robust regression model.
    Comparison groups
    Placebo Q2W Without Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0004 [47]
    Method
    Regression, Robust
    Parameter type
    Adjusted Mean Difference
    Point estimate
    -14.1
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -22.9
         upper limit
    -5.2
    Notes
    [47] - Threshold for significance ≤ 0.025.
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W + Statin
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Statistical analysis used multiple imputation approach followed by a robust regression model.
    Comparison groups
    Placebo Q2W with Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Number of subjects included in analysis
    464
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [48]
    Method
    Regression, Robust
    Parameter type
    Adjusted Mean Difference
    Point estimate
    -13.6
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -20.3
         upper limit
    -6.9
    Notes
    [48] - Threshold for significance ≤ 0.025.

    Secondary: Percent Change From Baseline in Apo A1 at Week 24 - ITT Analysis

    Close Top of page
    End point title
    Percent Change From Baseline in Apo A1 at Week 24 - ITT Analysis
    End point description
    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. Subjects of the ITT population (subjects with or without concomitant statin therapy) with one baseline and at least one post-baseline Apo A1 value on- or off-treatment (Apo A1 ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 24
    End point values
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects analysed
    146
    75
    292
    71
    34
    138
    Units: percent change
        least squares mean (standard error)
    2.9 ± 1
    6.5 ± 1.4
    5.5 ± 0.7
    -1.4 ± 1.3
    3.1 ± 1.9
    5.2 ± 0.9
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin v Placebo Q2W Without Concomitant Statin
    Number of subjects included in analysis
    209
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [49]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    6.6
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    3
         upper limit
    10.2
    Notes
    [49] - Threshold for significance ≤ 0.025.
    Statistical analysis title
    Placebo v Alirocumab 300mgQ4W/Up 150mgQ2W + Statin
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Placebo Q2W with Concomitant Statin v Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin
    Number of subjects included in analysis
    438
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0306 [50]
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference
    Point estimate
    2.7
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    -0.1
         upper limit
    5.4
    Notes
    [50] - Threshold for significance ≤ 0.025.

    Secondary: Percent Change From Baseline in Apo A1 at Week 12 - ITT Analysis

    Close Top of page
    End point title
    Percent Change From Baseline in Apo A1 at Week 12 - ITT Analysis
    End point description
    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. Apo A1 ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 24
    End point values
    Placebo Q2W with Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W with Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W with Concomitant Statin Placebo Q2W Without Concomitant Statin Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin
    Number of subjects analysed
    146
    75
    292
    71
    34
    138
    Units: percent change
        least squares mean (standard error)
    2.7 ± 1
    6.1 ± 1.4
    6 ± 0.7
    -1.8 ± 1.3
    2.4 ± 1.8
    4.6 ± 0.9
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product.
    Adverse event reporting additional description
    Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the ‘treatment-emergent period’ (the time from the first dose of study drug up to the last dose of study drug +70 days).
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    Placebo Q2W
    Reporting group description
    Two SC injections of placebo (for alirocumab) Q2W with or without stable statin therapy for 48 weeks.

    Reporting group title
    Alirocumab 75 mg Q2W/Up 150 mg Q2W
    Reporting group description
    Two SC injections of Alirocumab 150 mg Q4W alternating with 2 SC injections of placebo Q4W with or without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.

    Reporting group title
    Alirocumab 300 mg Q4W/Up 150 mg Q2W
    Reporting group description
    Two SC injections of Alirocumab 300 mg Q4W alternating with two SC injections of placebo Q4W with or without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.

    Serious adverse events
    Placebo Q2W Alirocumab 75 mg Q2W/Up 150 mg Q2W Alirocumab 300 mg Q4W/Up 150 mg Q2W
    Total subjects affected by serious adverse events
         subjects affected / exposed
    33 / 229 (14.41%)
    13 / 115 (11.30%)
    53 / 458 (11.57%)
         number of deaths (all causes)
    1
    1
    1
         number of deaths resulting from adverse events
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    0 / 229 (0.00%)
    1 / 115 (0.87%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 229 (0.00%)
    1 / 115 (0.87%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular compression
         subjects affected / exposed
    0 / 229 (0.00%)
    1 / 115 (0.87%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adrenocortical carcinoma
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fibrous histiocytoma
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intraductal papillary-mucinous carcinoma of pancreas
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    0 / 229 (0.00%)
    1 / 115 (0.87%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    0 / 229 (0.00%)
    1 / 115 (0.87%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal cancer
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of the tongue
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small cell lung cancer metastatic
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 229 (0.00%)
    1 / 115 (0.87%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Drug hypersensitivity
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery restenosis
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Impaired healing
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 229 (0.00%)
    1 / 115 (0.87%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-Cardiac chest pain
         subjects affected / exposed
    1 / 229 (0.44%)
    1 / 115 (0.87%)
    4 / 458 (0.87%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pelvic mass
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Completed suicide
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostatic obstruction
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Intentional overdose
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Tendon injury
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Traumatic fracture
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    2 / 458 (0.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    2 / 458 (0.44%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 229 (0.44%)
    1 / 115 (0.87%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    2 / 229 (0.87%)
    0 / 115 (0.00%)
    2 / 458 (0.44%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    2 / 458 (0.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    0 / 229 (0.00%)
    1 / 115 (0.87%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    2 / 458 (0.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    0 / 229 (0.00%)
    1 / 115 (0.87%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic cardiomyopathy
         subjects affected / exposed
    0 / 229 (0.00%)
    1 / 115 (0.87%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    3 / 229 (1.31%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    0 / 229 (0.00%)
    1 / 115 (0.87%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    3 / 229 (1.31%)
    0 / 115 (0.00%)
    3 / 458 (0.66%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nasal septum deviation
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary mass
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cervical radiculopathy
         subjects affected / exposed
    0 / 229 (0.00%)
    1 / 115 (0.87%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    2 / 458 (0.44%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Visual acuity reduced
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    0 / 229 (0.00%)
    1 / 115 (0.87%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticular perforation
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer perforation
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epiploic appendagitis
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Incarcerated inguinal hernia
         subjects affected / exposed
    0 / 229 (0.00%)
    1 / 115 (0.87%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Incarcerated umbilical hernia
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophageal spasm
         subjects affected / exposed
    0 / 229 (0.00%)
    1 / 115 (0.87%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Volvulus
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Calculus ureteric
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal failure acute
         subjects affected / exposed
    0 / 229 (0.00%)
    1 / 115 (0.87%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ureteric obstruction
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 229 (0.00%)
    1 / 115 (0.87%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Monarthritis
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Foot deformity
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    2 / 458 (0.44%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Polymyalgia rheumatica
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal column stenosis
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    2 / 458 (0.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 229 (0.00%)
    1 / 115 (0.87%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 229 (0.44%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemia
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 229 (0.00%)
    1 / 115 (0.87%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 229 (0.00%)
    1 / 115 (0.87%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute hepatitis c
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    0 / 229 (0.00%)
    1 / 115 (0.87%)
    0 / 458 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 229 (0.00%)
    0 / 115 (0.00%)
    2 / 458 (0.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 229 (0.44%)
    2 / 115 (1.74%)
    1 / 458 (0.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Placebo Q2W Alirocumab 75 mg Q2W/Up 150 mg Q2W Alirocumab 300 mg Q4W/Up 150 mg Q2W
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    118 / 229 (51.53%)
    55 / 115 (47.83%)
    229 / 458 (50.00%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    12 / 229 (5.24%)
    4 / 115 (3.48%)
    16 / 458 (3.49%)
         occurrences all number
    12
    4
    19
    Nervous system disorders
    Headache
         subjects affected / exposed
    13 / 229 (5.68%)
    6 / 115 (5.22%)
    29 / 458 (6.33%)
         occurrences all number
    21
    6
    40
    General disorders and administration site conditions
    Injection site reaction
         subjects affected / exposed
    16 / 229 (6.99%)
    10 / 115 (8.70%)
    74 / 458 (16.16%)
         occurrences all number
    22
    28
    126
    Non-Cardiac chest pain
         subjects affected / exposed
    5 / 229 (2.18%)
    6 / 115 (5.22%)
    7 / 458 (1.53%)
         occurrences all number
    6
    6
    7
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    15 / 229 (6.55%)
    7 / 115 (6.09%)
    19 / 458 (4.15%)
         occurrences all number
    16
    8
    20
    Diarrhoea
         subjects affected / exposed
    17 / 229 (7.42%)
    4 / 115 (3.48%)
    25 / 458 (5.46%)
         occurrences all number
    19
    6
    28
    Musculoskeletal and connective tissue disorders
    Muscle spasms
         subjects affected / exposed
    13 / 229 (5.68%)
    4 / 115 (3.48%)
    10 / 458 (2.18%)
         occurrences all number
    15
    5
    14
    Back pain
         subjects affected / exposed
    14 / 229 (6.11%)
    3 / 115 (2.61%)
    29 / 458 (6.33%)
         occurrences all number
    14
    3
    30
    Arthralgia
         subjects affected / exposed
    15 / 229 (6.55%)
    7 / 115 (6.09%)
    29 / 458 (6.33%)
         occurrences all number
    15
    7
    35
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    18 / 229 (7.86%)
    10 / 115 (8.70%)
    39 / 458 (8.52%)
         occurrences all number
    29
    11
    46
    Bronchitis
         subjects affected / exposed
    12 / 229 (5.24%)
    7 / 115 (6.09%)
    19 / 458 (4.15%)
         occurrences all number
    12
    7
    24
    Urinary tract infection
         subjects affected / exposed
    10 / 229 (4.37%)
    7 / 115 (6.09%)
    28 / 458 (6.11%)
         occurrences all number
    12
    7
    31
    Sinusitis
         subjects affected / exposed
    11 / 229 (4.80%)
    4 / 115 (3.48%)
    28 / 458 (6.11%)
         occurrences all number
    12
    4
    31
    Upper respiratory tract infection
         subjects affected / exposed
    18 / 229 (7.86%)
    8 / 115 (6.96%)
    41 / 458 (8.95%)
         occurrences all number
    19
    9
    53

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Oct 2013
    - The upper limit of LDL-C was changed from 190 mg/dL to 160 mg/dL for subjects at moderate CVD risk, for consistency with Adult Treatment Panel (ATP) III guidelines. - The term “statin inappropriate” was replaced with “statin intolerant”, to ensure the appropriate study population was enrolled. A definition for statin intolerance had been added. - The definitions for moderate, high, and very high CVD risk were added for clarity.
    26 Aug 2014
    - Primary efficacy single endpoint within each concomitant statin therapy population was modified (i.e, subjects who received concomitant statin therapy and subjects who did not receive concomitant statin therapy) to co-primary (i.e, 2) efficacy endpoints. - Efficacy alpha level was not adjusted in this study for the 2 co-primary endpoints, since study was to be considered positive within a given concomitant statin population if statistical significance was met for both co-primary endpoints. - The primary efficacy analysis population was modified to ITT population for the primary and secondary efficacy endpoints, which included assessments both on- and off- study treatment through analysis period. - Statistical methodology for primary and secondary efficacy analysis endpoints was modified as follows: An MMRM was to be used for 2 co-primary endpoints and for other continuous secondary endpoints anticipated to have normally distributed data; For continuous endpoints expected to had non-normally distributed data, robust regression method was to be used to test treatment group differences and missing data was to be handled using multiple imputation approach; For binary endpoints, logistic regression method was to be used to test treatment group differences and missing data was to be handled using multiple imputation approach. - Specified further the sensitivity analyses that was to be performed on primary efficacy endpoint. - Primary and key secondary endpoints was also to be analyzed in mITT population to assess drug effect during the study treatment period (on-treatment approach). - The list of key and other secondary efficacy endpoints and estimands (ITT estimand or on-treatment estimand) were adjusted. - Clarified that LDL-C, measured and calculated, was to be performed at weeks 0 and 24.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA