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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43857   clinical trials with a EudraCT protocol, of which   7284   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    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:
    Long-term Safety and Tolerability of REGN727/SAR236553 in High Cardiovascular Risk Patients with Hypercholesterolemia not Adequately Controlled with Their Lipid Modifying Therapy: a Randomized, Double-blind, Placebo-controlled Study

    Summary
    EudraCT number
    		 2011-002806-59
    Trial protocol
    		 BE   FI   SE   ES   PT   DE   CZ   NO   GB   NL   HU   IT   DK   BG  
    Global end of trial date
    19 Nov 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    16 Apr 2016
    First version publication date
    16 Apr 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    LTS11717
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01507831
    WHO universal trial number (UTN)
    		 U1111-1121-3928
    Other trial identifiers
    		 Study Name: ODYSSEY LONG TERM
    Sponsors
    Sponsor organisation name
    Sanofi aventis recherche & développement
    Sponsor organisation address
    1 avenue Pierre Brossolette, Chilly-Mazarin , France, 91380
    Public contact
    Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
    Scientific contact
    Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.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
    24 Dec 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Nov 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the long-term safety and tolerability of SAR236553(REGN727) in high cardiovascular (CV) risk subjects with hypercholesterolemia not adequately controlled with their lipid modifying therapy (LMT).
    Protection of trial subjects
    Subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject is participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.
    Background therapy
    		 All subjects received a stable dose of statin (rosuvastatin, simvastatin or atorvastatin) with or without other LMT as clinically indicated throughout the duration of study.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    06 Jan 2012
    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
    Netherlands: 68
    Country: Number of subjects enrolled
    Norway: 48
    Country: Number of subjects enrolled
    Poland: 146
    Country: Number of subjects enrolled
    Portugal: 8
    Country: Number of subjects enrolled
    Spain: 92
    Country: Number of subjects enrolled
    Sweden: 32
    Country: Number of subjects enrolled
    United Kingdom: 484
    Country: Number of subjects enrolled
    Belgium: 25
    Country: Number of subjects enrolled
    Bulgaria: 78
    Country: Number of subjects enrolled
    Czech Republic: 20
    Country: Number of subjects enrolled
    Denmark: 16
    Country: Number of subjects enrolled
    Finland: 20
    Country: Number of subjects enrolled
    France: 87
    Country: Number of subjects enrolled
    Germany: 139
    Country: Number of subjects enrolled
    Hungary: 78
    Country: Number of subjects enrolled
    Italy: 37
    Country: Number of subjects enrolled
    Argentina: 28
    Country: Number of subjects enrolled
    Canada: 63
    Country: Number of subjects enrolled
    Chile: 2
    Country: Number of subjects enrolled
    Colombia: 2
    Country: Number of subjects enrolled
    Israel: 8
    Country: Number of subjects enrolled
    Mexico: 50
    Country: Number of subjects enrolled
    Romania: 44
    Country: Number of subjects enrolled
    Russian Federation: 28
    Country: Number of subjects enrolled
    South Africa: 215
    Country: Number of subjects enrolled
    Ukraine: 38
    Country: Number of subjects enrolled
    United States: 485
    Worldwide total number of subjects
    2341
    EEA total number of subjects
    1422
    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)
    1474
    From 65 to 84 years
    859
    85 years and over
    8

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The study was conducted at 320 centers in 27 countries. Overall, 5144 subjects were screened between January 2012 and March 2013, 2801 of whom were screen failures. Screen failures were mainly due to exclusion criteria met. In addition 2 subjects received study drug but did not undergo randomization. They were excluded from analysis.

    Pre-assignment
    Screening details
    		 Randomization was stratified as per diagnosis of heterozygous familial hypercholesterolemia (heFH), prior history of myocardial infarction (MI) or ischemic stroke, intensity of statin treatment and geographic region. Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 1:2 ratio (placebo:alirocumab).

    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
    Arm description
    		 Placebo (for alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable lipid modifying therapy (LMT) for 78 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    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 SC injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person.

    Arm title
    		 Alirocumab 150 mg Q2W
    Arm description
    		 Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
    Arm type
    		 Experimental

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

    Number of subjects in period 1
    		Placebo Q2W Alirocumab 150 mg Q2W
    Started
    788
    1553
    Treated
    788
    1550
    Completed
    595
    1113
    Not completed
    193
    440
         Physician decision
    -
    4
         Adverse Event
    48
    113
         Selection criteria finally not met
    -
    1
         Poor compliance to protocol
    38
    60
         Site closure
    -
    3
         Last visit outside protocol visit window
    51
    143
         Consent withdrawn by subject
    34
    72
         Randomized but not treated
    -
    3
         Death
    6
    2
         Subject moved
    5
    19
         Unspecified
    3
    6
         Lost to follow-up
    3
    -
         Related to study drug administration
    5
    14

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo Q2W
    Reporting group description
    		 Placebo (for alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable lipid modifying therapy (LMT) for 78 weeks.

    Reporting group title
    Alirocumab 150 mg Q2W
    Reporting group description
    		 Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.

    Reporting group values
    		 Placebo Q2W Alirocumab 150 mg Q2W Total
    Number of subjects
    		 788 1553 2341
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 60.6 ± 10.4 60.4 ± 10.4 -
    Gender categorical
    Units: Subjects
        Female
    		 314 570 884
        Male
    		 474 983 1457
    Calculated LDL-C in mg/dL
    Calculated LDL-C in mg/dL from Friedewald formula (LDL-C = Total cholesterol - High-density lipoprotein cholesterol - [Triglyceride/5]).
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 121.9 ± 41.4 122.7 ± 42.6 -
    Calculated LDL-C in mmol/L
    Units: mmol/L
        arithmetic mean (standard deviation)
    		 3.157 ± 1.073 3.178 ± 1.102 -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo Q2W
    Reporting group description
    		 Placebo (for alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable lipid modifying therapy (LMT) for 78 weeks.

    Reporting group title
    Alirocumab 150 mg Q2W
    Reporting group description
    		 Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.

    Primary: Percentage of Subjects Who Experienced Adverse Events (AEs)

    		 Close Top of page
    End point title
    		 Percentage of Subjects Who Experienced Adverse Events (AEs) [1]
    End point 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). Safety population: all randomized subjects who received at least one dose or part of a dose of a study drug (treated).
    End point type
    Primary
    End point timeframe
    Up to 10 weeks after last study drug administration (maximum of 86 weeks)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Safety analyses were descriptive in nature.
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    788
    1550
    Units: percentage of subjects
    number (not applicable)
        Any AE
    82.5
    81
        Any Serious AE
    19.5
    18.7
        Any AE leading to death
    1.3
    0.5
        Any AE leading to treatment discontinuation
    5.8
    7.2
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis

    		 Close Top of page
    End point title
    		 Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis
    End point description
    Adjusted least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on­ or off-treatment were used in the model (ITT analysis). ITT population: all randomized subjects with one baseline and at least one post-baseline calculated LDL-C value on­ or off-treatment.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    780
    1530
    Units: percent change
        least squares mean (standard error)
    0.8 ± 1
    -61 ± 0.7
    Statistical analysis title
    		 Alirocumab 150 mg Q2W vs Placebo Q2W
    Statistical analysis description
    Alirocumab group was compared to placebo group using an appropriate contrast statement.
    Comparison groups
    Alirocumab 150 mg Q2W v Placebo Q2W
    Number of subjects included in analysis
    2310
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [2]
    Method
    		 Mixed models analysis
    Parameter type
    		 LS mean difference
    Point estimate
    -61.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -64.3
         upper limit
    		 -59.4
    Notes
    [2] - Threshold for significance ≤ 0.05.

    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 52 (i.e. up to 21 days after last injection) (on-treatment analysis). Modified ITT (mITT) population: all randomized and treated subjects with one baseline and at least one post-baseline calculated LDL-C value on-treatment.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    777
    1523
    Units: percent change
        least squares mean (standard error)
    0.7 ± 1
    -62.8 ± 0.7
    Statistical analysis title
    		 Alirocumab 150 mg Q2W vs Placebo Q2W
    Statistical analysis description
    A hierarchial 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 hierarchial testing sequence continued only when previous endpoint was statistically significant at 0.05 level.
    Comparison groups
    Alirocumab 150 mg Q2W v Placebo Q2W
    Number of subjects included in analysis
    2300
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [3]
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -63.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -65.9
         upper limit
    		 -61.2
    Notes
    [3] - Threshold for significance ≤ 0.05.

    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 52 regardless of status on- or off-treatment. ITT population.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    780
    1530
    Units: Percent Change
        least squares mean (standard error)
    1.5 ± 1
    -63.3 ± 0.7
    Statistical analysis title
    		 Alirocumab 150 mg Q2W vs Placebo Q2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Alirocumab 150 mg Q2W v Placebo Q2W
    Number of subjects included in analysis
    2310
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [4]
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -64.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -67.2
         upper limit
    		 -62.4
    Notes
    [4] - Threshold for significance ≤ 0.05.

    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 52 (i.e. up to 21 days after last injection). mITT population.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    777
    1523
    Units: percent change
        least squares mean (standard error)
    1.4 ± 1
    -64.2 ± 0.7
    Statistical analysis title
    		 Alirocumab 150 mg Q2W vs Placebo Q2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Alirocumab 150 mg Q2W v Placebo Q2W
    Number of subjects included in analysis
    2300
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [5]
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -65.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -67.9
         upper limit
    		 -63.2
    Notes
    [5] - Threshold for significance ≤ 0.05.

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

    		 Close Top of page
    End point title
    		 Percent Change From Baseline in Measured LDL-C at Week 24 - ITT Analysis
    End point description
    Measured LDL-C values via beta quantification method. Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment. Subjects of the ITT population with one baseline and at least one post-baseline measured LDL-C value on- or off-treatment.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    652
    1278
    Units: percent change
        least squares mean (standard error)
    3.5 ± 1.1
    -57.8 ± 0.8
    Statistical analysis title
    		 Alirocumab 150 mg Q2W vs Placebo Q2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Alirocumab 150 mg Q2W v Placebo Q2W
    Number of subjects included in analysis
    1930
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [6]
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -61.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -64
         upper limit
    		 -58.5
    Notes
    [6] - Threshold for significance ≤ 0.05.

    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 52 regardless of status on- or off-treatment. Subjects of the ITT population with one baseline and at least one post-baseline Apo B value on- or off-treatment (Apo B ITT population).
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    753
    1468
    Units: percent change
        least squares mean (standard error)
    1.2 ± 1
    -52.8 ± 0.7
    Statistical analysis title
    		 Alirocumab 150 mg Q2W vs Placebo Q2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Alirocumab 150 mg Q2W v Placebo Q2W
    Number of subjects included in analysis
    2221
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [7]
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -56.3
         upper limit
    		 -51.7
    Notes
    [7] - Threshold for significance ≤ 0.05.

    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 52 (i.e. up to 21 days after last injection). Subjects of the mITT population with one baseline and at least one post-baseline Apo-B value on-treatment (Apo B mITT population).
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    743
    1444
    Units: percent change
        least squares mean (standard error)
    1.2 ± 0.9
    -54.3 ± 0.7
    Statistical analysis title
    		 Alirocumab 150 mg Q2W vs Placebo Q2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Alirocumab 150 mg Q2W v Placebo Q2W
    Number of subjects included in analysis
    2187
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [8]
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -55.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -57.7
         upper limit
    		 -53.2
    Notes
    [8] - Threshold for significance ≤ 0.05.

    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 52 regardless of status on- or off-treatment. Subjects of the ITT population with one baseline and at least one post-baseline non-HDL-C value on- or off-treatment (non-HDL-C ITT population).
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    780
    1530
    Units: Percent Change
        least squares mean (standard error)
    0.7 ± 0.9
    -51.6 ± 0.6
    Statistical analysis title
    		 Alirocumab 150 mg Q2W vs Placebo Q2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Alirocumab 150 mg Q2W v Placebo Q2W
    Number of subjects included in analysis
    2310
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [9]
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -52.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -54.4
         upper limit
    		 -50.2
    Notes
    [9] - Threshold for significance ≤ 0.05.

    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 52 (i.e. up to 21 days after last injection). Subjects of the mITT population with one baseline and at least one post-baseline non-HDL-C value on-treatment (non-HDL-C mITT population).
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    777
    1523
    Units: percent change
        least squares mean (standard error)
    0.6 ± 0.9
    -53.1 ± 0.6
    Statistical analysis title
    		 Alirocumab 150 mg Q2W vs Placebo Q2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Alirocumab 150 mg Q2W v Placebo Q2W
    Number of subjects included in analysis
    2300
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [10]
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -53.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -55.7
         upper limit
    		 -51.6
    Notes
    [10] - Threshold for significance ≤ 0.05.

    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 52 regardless of status on- or off-treatment. Subjects of the ITT population with one baseline and at least one post-baseline Total-C value on- or off-treatment (Total-C ITT population).
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    780
    1530
    Units: percent change
        least squares mean (standard error)
    -0.3 ± 0.7
    -37.8 ± 0.5
    Statistical analysis title
    		 Alirocumab 150 mg Q2W vs Placebo Q2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Alirocumab 150 mg Q2W v Placebo Q2W
    Number of subjects included in analysis
    2310
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [11]
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -37.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -39.1
         upper limit
    		 -35.9
    Notes
    [11] - Threshold for significance ≤ 0.05.

    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 52 regardless of status on- or off-treatment. Apo B ITT population.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    753
    1468
    Units: percent change
        least squares mean (standard error)
    0.5 ± 0.9
    -55.5 ± 0.7
    Statistical analysis title
    		 Alirocumab 150 mg Q2W vs Placebo Q2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Alirocumab 150 mg Q2W v Placebo Q2W
    Number of subjects included in analysis
    2221
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [12]
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -56
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -58.3
         upper limit
    		 -53.7
    Notes
    [12] - Threshold for significance ≤ 0.05.

    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 52 regardless of status on- or off-treatment. Non-HDL-C ITT population.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    780
    1530
    Units: percent change
        least squares mean (standard error)
    0.9 ± 0.8
    -53.7 ± 0.6
    Statistical analysis title
    		 Alirocumab 150 mg Q2W vs Placebo Q2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Alirocumab 150 mg Q2W v Placebo Q2W
    Number of subjects included in analysis
    2310
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [13]
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -54.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -56.6
         upper limit
    		 -52.6
    Notes
    [13] - Threshold for significance ≤ 0.05.

    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 52 regardless of status on- or off-treatment. Total-C ITT population.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    780
    1530
    Units: percent change
        least squares mean (standard error)
    0.2 ± 0.6
    -38.8 ± 0.4
    Statistical analysis title
    		 Alirocumab 150 mg Q2W vs Placebo Q2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Alirocumab 150 mg Q2W v Placebo Q2W
    Number of subjects included in analysis
    2310
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [14]
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -40.4
         upper limit
    		 -37.5
    Notes
    [14] - Threshold for significance ≤ 0.05.

    Secondary: Percentage of Very High Cardiovascular (CV) Risk Subjects Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Subjects Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) 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 (1.81 mmol/L) or High CV Risk Subjects Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis
    End point description
    Very high CV risk: Heterozygous Familial Hypercholesterolemia(heFH) subjects with coronary heart disease(CHD) or CHD risk equivalents or non- Familial Hypercholesterolemia(FH). High CV risk: heFH subjects without CHD or CHD risk equivalents. CHD risk equivalent: peripheral arterial disease, ischemic stroke, moderate chronic kidney disease (estimated glomerular filtration rate, 30 to <60 ml/minute/1.73 m^2 of body-surface area), or diabetes mellitus + 2 or more additional risk factors (hypertension; ankle-brachial index of ≤0.90; microalbuminuria, macroalbuminuria, or a urinary dipstick result of >2+ protein; preproliferative or proliferative retinopathy or laser treatment for retinopathy; or family history of premature CHD). 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 52 regardless of status on- or off-treatment were included in imputation model. ITT population.
    End point type
    Secondary
    End point timeframe
    Up to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    780
    1530
    Units: percentage of subjects
        number (not applicable)
    8.5
    80.7
    Statistical analysis title
    		 Alirocumab 150 mg Q2W vs Placebo Q2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Multiple imputation approach followed by logistic regression model.
    Comparison groups
    Alirocumab 150 mg Q2W v Placebo Q2W
    Number of subjects included in analysis
    2310
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [15]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    71.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 51.6
         upper limit
    		 99.1
    Notes
    [15] - Threshold for significance ≤ 0.05.

    Secondary: Percentage of Very High CV Risk Subjects Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) 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 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 52 (i.e. up to 21 days after last injection). mITT population.
    End point type
    Secondary
    End point timeframe
    Up to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    777
    1523
    Units: percentage of subjects
        number (not applicable)
    8.5
    82.8
    Statistical analysis title
    		 Alirocumab 150 mg Q2W vs Placebo Q2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Multiple imputation approach followed by logistic regression model.
    Comparison groups
    Alirocumab 150 mg Q2W v Placebo Q2W
    Number of subjects included in analysis
    2300
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [16]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    93.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 66.1
         upper limit
    		 132
    Notes
    [16] - Threshold for significance ≤ 0.05.

    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 52 regardless of status on- or off-treatment were included in the imputation model. ITT population.
    End point type
    Secondary
    End point timeframe
    Up to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    780
    1530
    Units: percentage of subjects
        number (not applicable)
    8
    79.3
    Statistical analysis title
    		 Alirocumab 150 mg Q2W vs Placebo Q2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Multiple imputation approach followed by logistic regression model.
    Comparison groups
    Alirocumab 150 mg Q2W v Placebo Q2W
    Number of subjects included in analysis
    2310
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [17]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    74.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 53.3
         upper limit
    		 104.4
    Notes
    [17] - Threshold for significance ≤ 0.05.

    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 52 (i.e. up to 21 days after last injection). mITT population.
    End point type
    Secondary
    End point timeframe
    Up to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    777
    1523
    Units: percentage of subjects
        number (not applicable)
    8
    81.2
    Statistical analysis title
    		 Alirocumab 150 mg Q2W vs Placebo Q2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Multiple imputation approach followed by logistic regression model.
    Comparison groups
    Alirocumab 150 mg Q2W v Placebo Q2W
    Number of subjects included in analysis
    2300
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [18]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    97.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 68.2
         upper limit
    		 138.9
    Notes
    [18] - Threshold for significance ≤ 0.05.

    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 were obtained from multiple imputation approach followed by robust regression model for handling of missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment were included in the imputation model. ITT population.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    780
    1530
    Units: percent change
        arithmetic mean (standard error)
    -3.7 ± 1
    -29.3 ± 0.7
    Statistical analysis title
    		 Alirocumab 150 mg Q2W vs Placebo Q2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Multiple imputation approach followed by a robust regression model.
    Comparison groups
    Alirocumab 150 mg Q2W v Placebo Q2W
    Number of subjects included in analysis
    2310
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [19]
    Method
    		 Regression, Robust
    Parameter type
    		 Adjusted Mean Difference
    Point estimate
    -25.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -28.1
         upper limit
    		 -23.1
    Notes
    [19] - Threshold for significance ≤ 0.05.

    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 52 regardless of status on- or off-treatment. Subjects of the ITT population with one baseline and at least one post-baseline HDL-C value on- or off-treatment (HDL-C ITT population).
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    780
    1530
    Units: percent change
        least squares mean (standard error)
    -0.6 ± 0.5
    4 ± 0.4
    Statistical analysis title
    		 Alirocumab 150 mg Q2W vs Placebo Q2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Alirocumab 150 mg Q2W v Placebo Q2W
    Number of subjects included in analysis
    2310
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [20]
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    4.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.3
         upper limit
    		 5.9
    Notes
    [20] - Threshold for significance ≤ 0.05.

    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 52 regardless of status on-or off-treatment. ITT population.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    780
    1530
    Units: percent change
        arithmetic mean (standard error)
    1.8 ± 1.2
    -15.6 ± 0.8
    Statistical analysis title
    		 Alirocumab 150 mg Q2W vs Placebo Q2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Multiple imputation approach followed by a robust regression model.
    Comparison groups
    Alirocumab 150 mg Q2W v Placebo Q2W
    Number of subjects included in analysis
    2310
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [21]
    Method
    		 Regression, Robust
    Parameter type
    		 Adjusted Mean Difference
    Point estimate
    -17.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -20.1
         upper limit
    		 -14.6
    Notes
    [21] - Threshold for significance ≤ 0.05.

    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 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment. Subjects of the ITT population with one baseline and at least one post-baseline Apo A1 value on- or off-treatment (Apo A1 ITT population).
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    753
    1468
    Units: percent change
        least squares mean (standard error)
    1.2 ± 0.6
    4 ± 0.4
    Statistical analysis title
    		 Alirocumab 150 mg Q2W vs Placebo Q2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Alirocumab 150 mg Q2W v Placebo Q2W
    Number of subjects included in analysis
    2221
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [22]
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    2.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.6
         upper limit
    		 4.2
    Notes
    [22] - Threshold for significance ≤ 0.05.

    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 52 regardless of status on-or off-treatment. ITT population.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    780
    1530
    Units: percent change
        arithmetic mean (standard error)
    -3.1 ± 1
    -28.2 ± 0.7
    Statistical analysis title
    		 Alirocumab 150 mg Q2W vs Placebo Q2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Multiple imputation approach followed by a robust regression model.
    Comparison groups
    Alirocumab 150 mg Q2W v Placebo Q2W
    Number of subjects included in analysis
    2310
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [23]
    Method
    		 Regression, Robust
    Parameter type
    		 Adjusted Mean Difference
    Point estimate
    -25.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -27.4
         upper limit
    		 -22.7
    Notes
    [23] - Threshold for significance ≤ 0.05.

    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 52 regardless of status on- or off-treatment. HDL-C ITT population.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    780
    1530
    Units: percent change
        least squares mean (standard error)
    0.2 ± 0.5
    5.8 ± 0.4
    Statistical analysis title
    		 Alirocumab 150 mg Q2W vs Placebo Q2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Alirocumab 150 mg Q2W v Placebo Q2W
    Number of subjects included in analysis
    2310
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [24]
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    5.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.3
         upper limit
    		 6.8
    Notes
    [24] - Threshold for significance ≤ 0.05.

    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 52 regardless of status on-or off-treatment. ITT population.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    780
    1530
    Units: percent change
        arithmetic mean (standard error)
    1.2 ± 1.1
    -16.7 ± 0.8
    Statistical analysis title
    		 Alirocumab 150 mg Q2W vs Placebo Q2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Multiple imputation approach followed by a robust regression model.
    Comparison groups
    Alirocumab 150 mg Q2W v Placebo Q2W
    Number of subjects included in analysis
    2310
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [25]
    Method
    		 Regression, Robust
    Parameter type
    		 Adjusted Mean Difference
    Point estimate
    -17.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -20.5
         upper limit
    		 -15.3
    Notes
    [25] - Threshold for significance ≤ 0.05.

    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 52 regardless of status on- or off-treatment. Apo A1 ITT population.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    753
    1468
    Units: percent change
        least squares mean (standard error)
    0.6 ± 0.5
    4.6 ± 0.3
    Statistical analysis title
    		 Alirocumab 150 mg Q2W vs Placebo Q2W
    Statistical analysis description
    Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
    Comparison groups
    Alirocumab 150 mg Q2W v Placebo Q2W
    Number of subjects included in analysis
    2221
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [26]
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.8
         upper limit
    		 5.2
    Notes
    [26] - Threshold for significance ≤ 0.05.

    Other pre-specified: Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis

    		 Close Top of page
    End point title
    		 Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis
    End point description
    Adjusted LS means and standard errors at Week 52 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment. ITT population.
    End point type
    Other pre-specified
    End point timeframe
    From Baseline to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    780
    1530
    Units: percent change
        least squares mean (standard error)
    4.4 ± 1.2
    -56.8 ± 0.8
    No statistical analyses for this end point

    Other pre-specified: Percent Change From Baseline in Calculated LDL-C at Week 52 - On-Treatment Analysis

    		 Close Top of page
    End point title
    		 Percent Change From Baseline in Calculated LDL-C at Week 52 - On-Treatment Analysis
    End point description
    Adjusted LS means and standard errors at Week 52 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection). mITT population.
    End point type
    Other pre-specified
    End point timeframe
    From Baseline to Week 52
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    777
    1523
    Units: percent change
        least squares mean (standard error)
    4.6 ± 1.1
    -59.9 ± 0.8
    No statistical analyses for this end point

    Other pre-specified: Percent Change From Baseline in Calculated LDL-C at Week 78 - ITT Analysis

    		 Close Top of page
    End point title
    		 Percent Change From Baseline in Calculated LDL-C at Week 78 - ITT Analysis
    End point description
    Adjusted LS means and standard errors at Week 78 from MMRM model including all available post-baseline data from Week 4 to Week 78 regardless of status on- or off-treatment. ITT population.
    End point type
    Other pre-specified
    End point timeframe
    From Baseline to Week 78
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    780
    1530
    Units: percent change
        least squares mean (standard error)
    3.6 ± 1.3
    -52.4 ± 0.9
    No statistical analyses for this end point

    Other pre-specified: Percent Change From Baseline in Calculated LDL-C at Week 78 - On-Treatment Analysis

    		 Close Top of page
    End point title
    		 Percent Change From Baseline in Calculated LDL-C at Week 78 - On-Treatment Analysis
    End point description
    Adjusted LS means and standard errors at Week 78 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 78 (i.e. up to 21 days after last injection). mITT population.
    End point type
    Other pre-specified
    End point timeframe
    From Baseline to Week 78
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    777
    1523
    Units: percent change
        least squares mean (standard error)
    3.9 ± 1.2
    -58 ± 0.9
    No statistical analyses for this end point

    Other pre-specified: Percentage of Subjects Who Experienced Cardiovascular (CV) Events

    		 Close Top of page
    End point title
    		 Percentage of Subjects Who Experienced Cardiovascular (CV) Events
    End point description
    CV events included coronary heart disease (CHD) death; non-fatal myocardial infarction (MI); fatal and non-fatal ischemic stroke; unstable angina requiring hospitalization; congestive heart failure (CHF) requiring hospitalization; ischemia-driven coronary revascularization procedure. Reported events are CV events as confirmed by an independent Clinical Events Committee (CEC) that occurred during the treatment emergent period ( i.e. from first dose up to the last dose of study drug + 70 days). Safety population.
    End point type
    Other pre-specified
    End point timeframe
    Up to 10 weeks after last study drug administration (maximum of 86 weeks)
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    788
    1550
    Units: percentage of subjects
        number (not applicable)
    5.1
    4.6
    No statistical analyses for this end point

    Post-hoc: Percentage of Subjects Who Experienced Major Adverse CV Events

    		 Close Top of page
    End point title
    		 Percentage of Subjects Who Experienced Major Adverse CV Events
    End point description
    Major adverse CV events were defined as all adverse CV events except Congestive heart failure (CHF) requiring hospitalization; and ischemia-driven coronary revascularization procedure. Safety population.
    End point type
    Post-hoc
    End point timeframe
    Up to 10 weeks after last study drug administration (maximum of 86 weeks)
    End point values
    		 Placebo Q2W Alirocumab 150 mg Q2W
    Number of subjects analysed
    788
    1550
    Units: percentage of subjects
        number (not applicable)
    3.3
    1.7
    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 86 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product.
    Adverse event reporting additional description
    Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'the treatment emergent period’ (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
    		 Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.

    Reporting group title
    Alirocumab 150 Q2W
    Reporting group description
    		 Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.

    Serious adverse events
    		 Placebo Q2W Alirocumab 150 Q2W
    Total subjects affected by serious adverse events
         subjects affected / exposed
    154 / 788 (19.54%)
    290 / 1550 (18.71%)
         number of deaths (all causes)
    8
    7
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute Myeloid Leukaemia
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Adenocarcinoma Of Colon
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    B-Cell Lymphoma
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basal Cell Carcinoma
         subjects affected / exposed
    2 / 788 (0.25%)
    8 / 1550 (0.52%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign Ovarian Tumour
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder Cancer
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast Cancer
         subjects affected / exposed
    1 / 788 (0.13%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Choroid Melanoma
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic Lymphocytic Leukaemia
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon Cancer
         subjects affected / exposed
    0 / 788 (0.00%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ductal Adenocarcinoma Of Pancreas
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Endometrial Cancer
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endometrial Cancer Stage I
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngeal Squamous Cell Carcinoma
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lentigo Maligna
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lip Squamous Cell Carcinoma
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant Melanoma
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuroendocrine Carcinoma Metastatic
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-Hodgkin's Lymphoma Metastatic
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Oesophageal Carcinoma
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic Carcinoma
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pancreatic Carcinoma Metastatic
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleomorphic Liposarcoma
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate Cancer
         subjects affected / exposed
    3 / 788 (0.38%)
    3 / 1550 (0.19%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate Cancer Metastatic
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate Cancer Recurrent
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal Adenocarcinoma
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal Cancer
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin Cancer
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous Cell Carcinoma
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous Cell Carcinoma Of Lung
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous Cell Carcinoma Of Skin
         subjects affected / exposed
    0 / 788 (0.00%)
    3 / 1550 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous Cell Carcinoma Of The Oral Cavity
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tongue Cancer Metastatic
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Aortic Aneurysm
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic Aneurysm Rupture
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Aortic Dissection
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Deep Vein Thrombosis
         subjects affected / exposed
    0 / 788 (0.00%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Extremity Necrosis
         subjects affected / exposed
    1 / 788 (0.13%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral Artery Aneurysm
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    2 / 788 (0.25%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive Crisis
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 788 (0.13%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemic Shock
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iliac Artery Occlusion
         subjects affected / exposed
    0 / 788 (0.00%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphocele
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral Arterial Occlusive Disease
         subjects affected / exposed
    1 / 788 (0.13%)
    4 / 1550 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral Artery Stenosis
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral Ischaemia
         subjects affected / exposed
    2 / 788 (0.25%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral Vascular Disorder
         subjects affected / exposed
    1 / 788 (0.13%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subclavian Artery Stenosis
         subjects affected / exposed
    1 / 788 (0.13%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombophlebitis
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion Spontaneous
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest Pain
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary Artery Restenosis
         subjects affected / exposed
    1 / 788 (0.13%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Device Failure
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device Malfunction
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multi-Organ Failure
         subjects affected / exposed
    4 / 788 (0.51%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 3
    0 / 1
    Non-Cardiac Chest Pain
         subjects affected / exposed
    2 / 788 (0.25%)
    13 / 1550 (0.84%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral Artery Restenosis
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Cytokine Release Syndrome
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug Hypersensitivity
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypersensitivity
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Galactorrhoea
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Menorrhagia
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metrorrhagia
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian Cyst
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatomegaly
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine Haemorrhage
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute Respiratory Distress Syndrome
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute Respiratory Failure
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    1 / 788 (0.13%)
    3 / 1550 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis Chronic
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic Obstructive Pulmonary Disease
         subjects affected / exposed
    6 / 788 (0.76%)
    4 / 1550 (0.26%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural Effusion
         subjects affected / exposed
    2 / 788 (0.25%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngeal Oedema
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia Aspiration
         subjects affected / exposed
    1 / 788 (0.13%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pulmonary Embolism
         subjects affected / exposed
    1 / 788 (0.13%)
    6 / 1550 (0.39%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary Hypertension
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary Oedema
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Alcohol Abuse
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bipolar Disorder
         subjects affected / exposed
    0 / 788 (0.00%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Confusional State
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    2 / 788 (0.25%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression Suicidal
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Major Depression
         subjects affected / exposed
    1 / 788 (0.13%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental Disorder Due To A General Medical Condition
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental Status Changes
         subjects affected / exposed
    2 / 788 (0.25%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Panic Attack
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicidal Ideation
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicide Attempt
         subjects affected / exposed
    1 / 788 (0.13%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood Creatine Phosphokinase Increased
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electrocardiogram Qt Prolonged
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electrocardiogram St Segment Depression
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Troponin Increased
         subjects affected / exposed
    1 / 788 (0.13%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Abdominal Injury
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Accidental Overdose
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle Fracture
         subjects affected / exposed
    0 / 788 (0.00%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arterial Injury
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clavicle Fracture
         subjects affected / exposed
    1 / 788 (0.13%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral Neck Fracture
         subjects affected / exposed
    1 / 788 (0.13%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur Fracture
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fibula Fracture
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hand Fracture
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip Fracture
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus Fracture
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intentional Overdose
         subjects affected / exposed
    1 / 788 (0.13%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint Injury
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laceration
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ligament Rupture
         subjects affected / exposed
    2 / 788 (0.25%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle Rupture
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle Strain
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post Procedural Haematoma
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post Procedural Haematuria
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative Respiratory Failure
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib Fracture
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal Cord Injury
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendon Rupture
         subjects affected / exposed
    0 / 788 (0.00%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tibia Fracture
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic Haematoma
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic Intracranial Haemorrhage
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Vascular Pseudoaneurysm
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wrist Fracture
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Hypertrophic Cardiomyopathy
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thyroglossal Cyst
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute Coronary Syndrome
         subjects affected / exposed
    6 / 788 (0.76%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute Myocardial Infarction
         subjects affected / exposed
    11 / 788 (1.40%)
    9 / 1550 (0.58%)
         occurrences causally related to treatment / all
    0 / 13
    1 / 10
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Angina Pectoris
         subjects affected / exposed
    6 / 788 (0.76%)
    9 / 1550 (0.58%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina Unstable
         subjects affected / exposed
    9 / 788 (1.14%)
    29 / 1550 (1.87%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 31
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic Valve Stenosis
         subjects affected / exposed
    1 / 788 (0.13%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriosclerosis Coronary Artery
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial Fibrillation
         subjects affected / exposed
    7 / 788 (0.89%)
    9 / 1550 (0.58%)
         occurrences causally related to treatment / all
    0 / 8
    1 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial Flutter
         subjects affected / exposed
    1 / 788 (0.13%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular Block
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular Block Second Degree
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 788 (0.00%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac Arrest
         subjects affected / exposed
    0 / 788 (0.00%)
    3 / 1550 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac Failure
         subjects affected / exposed
    3 / 788 (0.38%)
    4 / 1550 (0.26%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac Failure Chronic
         subjects affected / exposed
    0 / 788 (0.00%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac Failure Congestive
         subjects affected / exposed
    3 / 788 (0.38%)
    4 / 1550 (0.26%)
         occurrences causally related to treatment / all
    0 / 4
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiogenic Shock
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary Artery Disease
         subjects affected / exposed
    3 / 788 (0.38%)
    10 / 1550 (0.65%)
         occurrences causally related to treatment / all
    0 / 3
    2 / 10
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Coronary Artery Occlusion
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary Artery Stenosis
         subjects affected / exposed
    2 / 788 (0.25%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dressler's Syndrome
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Extrasystoles
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive Heart Disease
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Ischaemic Cardiomyopathy
         subjects affected / exposed
    1 / 788 (0.13%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial Infarction
         subjects affected / exposed
    4 / 788 (0.51%)
    4 / 1550 (0.26%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Myocardial Ischaemia
         subjects affected / exposed
    2 / 788 (0.25%)
    3 / 1550 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pleuropericarditis
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sick Sinus Syndrome
         subjects affected / exposed
    1 / 788 (0.13%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Silent Myocardial Infarction
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus Bradycardia
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular Tachycardia
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular Fibrillation
         subjects affected / exposed
    2 / 788 (0.25%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Ventricular Tachycardia
         subjects affected / exposed
    1 / 788 (0.13%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Altered State Of Consciousness
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ataxia
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain Stem Infarction
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid Arteriosclerosis
         subjects affected / exposed
    1 / 788 (0.13%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid Artery Stenosis
         subjects affected / exposed
    1 / 788 (0.13%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carpal Tunnel Syndrome
         subjects affected / exposed
    0 / 788 (0.00%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebellar Infarction
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral Haemorrhage
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral Infarction
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular Accident
         subjects affected / exposed
    0 / 788 (0.00%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Convulsion
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dementia
         subjects affected / exposed
    1 / 788 (0.13%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Demyelination
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysarthria
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frontotemporal Dementia
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Generalised Tonic-Clonic Seizure
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic Stroke
         subjects affected / exposed
    0 / 788 (0.00%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Headache
         subjects affected / exposed
    1 / 788 (0.13%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoaesthesia
         subjects affected / exposed
    2 / 788 (0.25%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemic Coma
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic Stroke
         subjects affected / exposed
    1 / 788 (0.13%)
    5 / 1550 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lacunar Infarction
         subjects affected / exposed
    0 / 788 (0.00%)
    3 / 1550 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Loss Of Consciousness
         subjects affected / exposed
    0 / 788 (0.00%)
    3 / 1550 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Miller Fisher Syndrome
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myoclonic Epilepsy
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nerve Root Compression
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Optic Neuritis
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parkinson's Disease
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    1 / 788 (0.13%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    6 / 788 (0.76%)
    11 / 1550 (0.71%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient Ischaemic Attack
         subjects affected / exposed
    0 / 788 (0.00%)
    7 / 1550 (0.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Coagulopathy
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iron Deficiency Anaemia
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spontaneous Haematoma
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo Positional
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Age-Related Macular Degeneration
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blepharochalasis
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cataract
         subjects affected / exposed
    1 / 788 (0.13%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic Retinopathy
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine Ophthalmopathy
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Macular Hole
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Open Angle Glaucoma
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal Artery Occlusion
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal Haemorrhage
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal Vein Occlusion
         subjects affected / exposed
    2 / 788 (0.25%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal Vein Thrombosis
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Visual Impairment
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vitreous Detachment
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal Adhesions
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal Hernia
         subjects affected / exposed
    1 / 788 (0.13%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal Hernia Obstructive
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal Pain
         subjects affected / exposed
    1 / 788 (0.13%)
    3 / 1550 (0.19%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcoholic Pancreatitis
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Barrett's Oesophagus
         subjects affected / exposed
    1 / 788 (0.13%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    3 / 788 (0.38%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum Intestinal
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal Ulcer Haemorrhage
         subjects affected / exposed
    1 / 788 (0.13%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    2 / 788 (0.25%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroduodenal Haemorrhage
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hiatus Hernia
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal Obstruction
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal Perforation
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intussusception
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large Intestine Polyp
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis Acute
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis Chronic
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis Relapsing
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peptic Ulcer Haemorrhage
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Umbilical Hernia
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper Gastrointestinal Haemorrhage
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile Duct Stone
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    1 / 788 (0.13%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis Acute
         subjects affected / exposed
    0 / 788 (0.00%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 788 (0.00%)
    3 / 1550 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug-Induced Liver Injury
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic Steatosis
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatocellular Injury
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dermatitis Allergic
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypersensitivity Vasculitis
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Bladder Spasm
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Calculus Ureteric
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Calculus Urinary
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis Interstitial
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic Nephropathy
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    1 / 788 (0.13%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertonic Bladder
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 788 (0.13%)
    3 / 1550 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal Artery Stenosis
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal Failure Acute
         subjects affected / exposed
    3 / 788 (0.38%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal Failure Chronic
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal Impairment
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal Pain
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteric Stenosis
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urethral Stenosis
         subjects affected / exposed
    0 / 788 (0.00%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary Retention
         subjects affected / exposed
    1 / 788 (0.13%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Thyrotoxic Crisis
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Ankylosing Spondylitis
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthralgia
         subjects affected / exposed
    0 / 788 (0.00%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    0 / 788 (0.00%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back Pain
         subjects affected / exposed
    1 / 788 (0.13%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral Disc Degeneration
         subjects affected / exposed
    1 / 788 (0.13%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral Disc Protrusion
         subjects affected / exposed
    0 / 788 (0.00%)
    4 / 1550 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar Spinal Stenosis
         subjects affected / exposed
    2 / 788 (0.25%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal Chest Pain
         subjects affected / exposed
    3 / 788 (0.38%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myositis
         subjects affected / exposed
    0 / 788 (0.00%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    3 / 788 (0.38%)
    8 / 1550 (0.52%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteochondrosis
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polymyalgia Rheumatica
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rotator Cuff Syndrome
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal Column Stenosis
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal Osteoarthritis
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertebral Foraminal Stenosis
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 788 (0.13%)
    3 / 1550 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium Difficile Colitis
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cystitis Viral
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device Related Infection
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic Foot Infection
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 788 (0.00%)
    4 / 1550 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    2 / 788 (0.25%)
    5 / 1550 (0.32%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis Viral
         subjects affected / exposed
    0 / 788 (0.00%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal Viral Infection
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Groin Abscess
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Helicobacter Gastritis
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incision Site Infection
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infective Exacerbation Of Chronic Obstructive Airways Disease
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    2 / 788 (0.25%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Labyrinthitis
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lobar Pneumonia
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower Respiratory Tract Infection
         subjects affected / exposed
    1 / 788 (0.13%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lyme Disease
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenic Sepsis
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    1 / 788 (0.13%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    7 / 788 (0.89%)
    6 / 1550 (0.39%)
         occurrences causally related to treatment / all
    0 / 7
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia Pneumococcal
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia Staphylococcal
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post Procedural Sepsis
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Postoperative Wound Infection
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 788 (0.00%)
    3 / 1550 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis Acute
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 788 (0.13%)
    5 / 1550 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic Shock
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Upper Respiratory Tract Infection
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary Tract Infection
         subjects affected / exposed
    0 / 788 (0.00%)
    3 / 1550 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary Tract Infection Pseudomonal
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound Abscess
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes Mellitus
         subjects affected / exposed
    2 / 788 (0.25%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic Ketoacidosis
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 788 (0.13%)
    2 / 1550 (0.13%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 788 (0.13%)
    3 / 1550 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lactic Acidosis
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lipomatosis
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour Lysis Syndrome
         subjects affected / exposed
    1 / 788 (0.13%)
    0 / 1550 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Type 2 Diabetes Mellitus
         subjects affected / exposed
    0 / 788 (0.00%)
    1 / 1550 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo Q2W Alirocumab 150 Q2W
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    366 / 788 (46.45%)
    707 / 1550 (45.61%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    44 / 788 (5.58%)
    76 / 1550 (4.90%)
         occurrences all number
    47
    103
    General disorders and administration site conditions
    Injection Site Reaction
         subjects affected / exposed
    33 / 788 (4.19%)
    91 / 1550 (5.87%)
         occurrences all number
    42
    184
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    45 / 788 (5.71%)
    89 / 1550 (5.74%)
         occurrences all number
    49
    112
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    52 / 788 (6.60%)
    80 / 1550 (5.16%)
         occurrences all number
    60
    87
    Back Pain
         subjects affected / exposed
    52 / 788 (6.60%)
    84 / 1550 (5.42%)
         occurrences all number
    57
    90
    Myalgia
         subjects affected / exposed
    23 / 788 (2.92%)
    84 / 1550 (5.42%)
         occurrences all number
    31
    94
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    40 / 788 (5.08%)
    83 / 1550 (5.35%)
         occurrences all number
    45
    102
    Influenza
         subjects affected / exposed
    43 / 788 (5.46%)
    88 / 1550 (5.68%)
         occurrences all number
    53
    103
    Nasopharyngitis
         subjects affected / exposed
    103 / 788 (13.07%)
    209 / 1550 (13.48%)
         occurrences all number
    143
    267
    Upper Respiratory Tract Infection
         subjects affected / exposed
    68 / 788 (8.63%)
    114 / 1550 (7.35%)
         occurrences all number
    79
    136
    Urinary Tract Infection
         subjects affected / exposed
    54 / 788 (6.85%)
    87 / 1550 (5.61%)
         occurrences all number
    84
    121

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    29 Nov 2011
    Additional assessments were added for a possible significant lowering of LDL-C by alirocumab, including adrenal function monitoring and neurological examinations. The monitoring plan for LDL-C <25 mg/dL (0.65 mmol/L) was revised accordingly; Hepatitis C testing was added to the end of the treatment visit because some data suggested that proprotein convertase subtilisin kexin type 9 (PCSK9) negatively regulates CD81 levels ; An ophthalmologic sub-study in a sub-set of subjects and color vision testing in all subjects was added due to the observation of optic nerve degeneration and chorioretinal lesions in 26-week toxicology studies in rats and monkeys, respectively; Measured LDL-C via beta quantification method was added at key efficacy time points due to potential inaccuracies of calculated LDL-C, when the LDL-C level reaches <50 mg/dL (1.30 mmol/L); The exclusion criteria related to LDL-C was changed to <100 mg/dL (2.59 mmol/L), since this exclusion criterion was used in the phase 2 studies, it was viewed as more appropriate to keep the same inclusion criterion in LTS11717, when using the dose of 150 mg every 2 weeks.
    11 May 2012
    The exclusion criteria of LDL-C >160 mg/dL (4.14 mmol/L) at screening and subject only on statin monotherapy without additional LMT were deleted. Such subjects could be included, but an explanation for no second LMT was to be provided; A guideline was added for medical work up for cases of low hemoglobin (post-baseline decrease of ≥15 g/dL), and an algorithm was added for the identification of cases of hemolytic anemia; Clearer guidance was provided on follow-up of anti-alirocumab antibodies to maintain the integrity of the double-blind in the study; Criterion to meet an LDL-C rescue alert was modified; Clinical criteria for diagnosis of heFH for study eligibility was clarified; A CHD risk equivalent was added to include moderate chronic kidney disease as defined by estimated glomerular filtration rate (eGFR) 30 to <60 mL/min/1.73 m2 for 3 months or more consistently with the 2011 Guidelines for the Management of Dyslipidaemias by The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology and the European Atherosclerosis Society; Recent information on rare cases of hypersensitivity was added as well as details on monitoring, reporting, and collecting information to better document potential allergy events.
    12 Nov 2012
    Exclusion criterion related to LDL-C was changed from <100 mg/dL (2.59 mmol/L) to <70 mg/dL (1.81 mmol/L), thereby including a subject population that more completely represents the expected future clinical use of the compound; Assessments regarding vitamins A, D, and K as other fat soluble vitamins and gonadal hormones assessments were clarified to ensure the integrity of the blood sample and information collected; The description of adrenal function monitoring was updated to recommend early morning sampling to best evaluate this parameter.
    26 Feb 2014
    The primary efficacy analysis population was changed to the ITT population and the statistical analysis methodology for the primary and secondary efficacy analysis endpoints was changed to ITT analysis performed on the ITT population and including all lipid values (on-treatment and off-treatment); The language regarding the recording of injection site reactions not related to IMP was updated to clarify the reporting of local injection site reactions.

    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.
    Manual reclassification was done by the Sponsor for the "other reasons" of non-completion of study as specified in the electronic case report (eCRF) form.

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/25773378
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Wed Apr 24 18:02:45 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA