Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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


    The EU Clinical Trials Register currently displays   38147   clinical trials with a EudraCT protocol, of which   6265   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    An 8-Week Open-Label, Sequential, Repeated Dose-Finding Study to Evaluate the Efficacy and Safety of Alirocumab in Children and Adolescents with Heterozygous Familial Hypercholesterolemia Followed by an Extension Phase

    Summary
    EudraCT number
    2015-003766-85
    Trial protocol
    SE   ES   CZ   FR   Outside EU/EEA  
    Global end of trial date
    22 Feb 2019

    Results information
    Results version number
    v1(current)
    This version publication date
    01 Sep 2019
    First version publication date
    01 Sep 2019
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    DFI14223
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02890992
    WHO universal trial number (UTN)
    U1111-1178-4764
    Other trial identifiers
    STUDY NAME: ODYSSEY KIDS
    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)
    Yes
    EMA paediatric investigation plan number(s)
    EMEA-001169-PIP01-11
    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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    03 May 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Feb 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the effect of alirocumab administered every 2 weeks (Q2W) or every 4 weeks (Q4W) on low-density lipoprotein cholesterol (LDL-C) levels after 8 weeks of treatment in heterozygous familial hypercholesterolemia (heFH) subjects aged of 8 to 17 years, with LDL-C greater than or equals (>=) 130 milligram/deciLitre (mg/dL) (3.37 millimoles/Litre [mmol/L]) on optimal stable daily dose of statin therapy ± other lipid modifying therapies (LMTs) or a stable dose of non-statin LMTs in case of intolerance to statins, for at least 4 weeks prior to the screening period.
    Protection of trial subjects
    The study was conducted by investigators experienced in the treatment of pediatric subjects. The parent(s) or guardian(s) as well as the children were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time. In addition to the consent form for the parent(s)/guardian(s), an assent form in child-appropriate language was provided and explained to the child. Repeated invasive procedures were minimized. The number of blood samples as well as the amount of blood drawn were adjusted according to age and weight. A topical anesthesia may have been used to minimize distress and discomfort.
    Background therapy
    Statins, Cholesterol absorption inhibitors (ezetimibe), Bile acid-binding sequestrants (such as cholestyramine, colestipol, colesevelam), Nicotinic acid, Fenofibrate, Omega-3 fatty acids (>=1000 mg daily) were used as background therapy.
    Evidence for comparator
    -
    Actual start date of recruitment
    30 Jun 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Norway: 1
    Country: Number of subjects enrolled
    Spain: 5
    Country: Number of subjects enrolled
    Sweden: 2
    Country: Number of subjects enrolled
    Czech Republic: 11
    Country: Number of subjects enrolled
    France: 1
    Country: Number of subjects enrolled
    South Africa: 1
    Country: Number of subjects enrolled
    Netherlands: 8
    Country: Number of subjects enrolled
    Canada: 3
    Country: Number of subjects enrolled
    Russian Federation: 4
    Country: Number of subjects enrolled
    United States: 6
    Worldwide total number of subjects
    42
    EEA total number of subjects
    28
    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)
    13
    Adolescents (12-17 years)
    29
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    The study was conducted at 16 sites in 10 countries. Overall 63 subjects were screened between 15 September 2016 and 13 June 2018, of whom 21 subjects were screen failures. Screen failures were mainly due to exclusion criteria met.

    Pre-assignment
    Screening details
    A total of 42 subjects were included in this study.

    Period 1
    Period 1 title
    12 Weeks Open-Label Dose Finding Period
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg
    Arm description
    Subjects with body weight less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 30 milligram(mg) administered every 2 weeks (Q2W) up to 8 weeks added to lipid modifying therapy (LMT).
    Arm type
    Experimental

    Investigational medicinal product name
    Alirocumab
    Investigational medicinal product code
    SAR236553, REGN727
    Other name
    Praluent®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Alirocumab administered as SC injection of 0.5 millilitre (mL) in the abdomen, thigh, or outer area of the upper arm.

    Arm title
    Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg
    Arm description
    Subjects with body weight greater than or equal to (>=) 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT.
    Arm type
    Experimental

    Investigational medicinal product name
    Alirocumab
    Investigational medicinal product code
    SAR236553, REGN727
    Other name
    Praluent®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Alirocumab administered as SC injection of 0.5 mL in the abdomen, thigh, or outer area of the upper arm.

    Arm title
    Cohort 2 - Alirocumab 40 mg Q2W: <50 kg
    Arm description
    Subjects with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT.
    Arm type
    Experimental

    Investigational medicinal product name
    Alirocumab
    Investigational medicinal product code
    SAR236553, REGN727
    Other name
    Praluent®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Alirocumab administered as SC injection of 0.5 mL in the abdomen, thigh, or outer area of the upper arm.

    Arm title
    Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg
    Arm description
    Subjects with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT.
    Arm type
    Experimental

    Investigational medicinal product name
    Alirocumab
    Investigational medicinal product code
    SAR236553, REGN727
    Other name
    Praluent®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Alirocumab administered as SC injection of 0.5 mL in the abdomen, thigh, or outer area of the arm.

    Arm title
    Cohort 3 - Alirocumab 75 mg Q4W: <50 kg
    Arm description
    Subjects with body weight < 50 kg received SC injection of alirocumab 75 mg administered every 4 weeks (Q4W) up to 8 weeks added to LMT.
    Arm type
    Experimental

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

    Arm title
    Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg
    Arm description
    Subjects with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT.
    Arm type
    Experimental

    Investigational medicinal product name
    Alirocumab
    Investigational medicinal product code
    SAR236553, REGN727
    Other name
    Praluent®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Alirocumab administered as SC injection of 1 mL in the abdomen, thigh, or outer area of the upper arm, Q4W.

    Arm title
    Cohort 4 - Alirocumab 150 mg Q4W: <50 kg
    Arm description
    Subjects with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT.
    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 of 1 mL in the abdomen, thigh, or outer area of the upper arm.

    Arm title
    Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Arm description
    Subjects with body weight >=50 kg received SC injection of Alirocumab 300 mg administered Q4W up to 12 weeks added to LMT.
    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 of 1 mL in the abdomen, thigh, or outer area of the upper arm.

    Number of subjects in period 1
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Started
    4
    6
    4
    6
    6
    5
    6
    5
    Treated
    4
    6
    4
    6
    6
    5
    6
    5
    Completed
    4
    6
    4
    6
    6
    5
    6
    5
    Period 2
    Period 2 title
    130 Weeks Open-Label Extension Period
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg
    Arm description
    Period 1: Subjects with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W up to 8 weeks added to LMT. Period 2: Subjects with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W from Week 16 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still < 50 kg, subjects received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg subjects received SC injection of alirocumab 75 mg administered Q2W until Week 130.
    Arm type
    Experimental

    Investigational medicinal product name
    Alirocumab
    Investigational medicinal product code
    SAR236553, REGN727
    Other name
    Praluent®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Alirocumab administered as SC injection of 0.5 millilitre (mL) in the abdomen, thigh, or outer area of the upper arm.

    Arm title
    Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg
    Arm description
    Period 1: Subjects with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. Period 2: Subjects with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W from Week 16 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130.
    Arm type
    Experimental

    Investigational medicinal product name
    Alirocumab
    Investigational medicinal product code
    SAR236553, REGN727
    Other name
    Praluent®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Alirocumab administered as SC injection of 0.5 mL in the abdomen, thigh, or outer area of the upper arm.

    Arm title
    Cohort 2 - Alirocumab 40 mg Q2W: <50 kg
    Arm description
    Period 1: Subjects with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. Period 2: Subjects with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W from Week 16 until switch of dosage in Cohorts 1 and 3. If body weight was still < 50 kg, subjects continued to receive SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg subjects received SC injection of alirocumab 75 mg administered Q2W until Week 130.
    Arm type
    Experimental

    Investigational medicinal product name
    Alirocumab
    Investigational medicinal product code
    SAR236553, REGN727
    Other name
    Praluent®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Alirocumab administered as SC injection of 0.5 mL in the abdomen, thigh, or outer area of the upper arm.

    Arm title
    Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg
    Arm description
    Period 1: Subjects with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. Period 2: Subjects with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W from Week 16 until Week 130.
    Arm type
    Experimental

    Investigational medicinal product name
    Alirocumab
    Investigational medicinal product code
    SAR236553, REGN727
    Other name
    Praluent®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Alirocumab administered as SC injection of 0.5 mL in the abdomen, thigh, or outer area of the arm.

    Arm title
    Cohort 3 - Alirocumab 75 mg Q4W: <50 kg
    Arm description
    Period 1: Subjects with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W up to 8 weeks added to LMT. Period 2: Subjects with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W from Week 14 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still < 50 kg, subjects received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg subjects received SC injection of alirocumab 75 mg administered Q2W until Week 130.
    Arm type
    Experimental

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

    Arm title
    Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg
    Arm description
    Period 1: Subjects with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. Period 2: Subjects with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 14 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130.
    Arm type
    Experimental

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

    Arm title
    Cohort 4 - Alirocumab 150 mg Q4W: <50 kg
    Arm description
    Period 1: Subjects with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. Period 2: Subjects with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 12 until Week 48.
    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 of 1 mL in the abdomen, thigh, or outer area of the upper arm

    Arm title
    Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Arm description
    Period 1: Subjects with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. Period 2: Subjects with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W from Week 12 until Week 48.
    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 of 1 mL in the abdomen, thigh, or outer area of the upper arm.

    Number of subjects in period 2 [1]
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Started
    3
    6
    4
    6
    6
    5
    6
    5
    Treated
    3
    6
    4
    6
    6
    5
    5
    4
    Completed
    3
    3
    4
    6
    6
    5
    5
    4
    Not completed
    0
    3
    0
    0
    0
    0
    1
    1
         Included but not treated
    -
    -
    -
    -
    -
    -
    1
    1
         Other than specified
    -
    2
    -
    -
    -
    -
    -
    -
         Adverse Event
    -
    1
    -
    -
    -
    -
    -
    -
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Out of 4 subjects from Period 1 of arm 'Cohort 1 - Alirocumab 30 mg Q2W: <50 kg', 3 subjects entered into the open-label extension (OLE) period.

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg
    Reporting group description
    Subjects with body weight less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 30 milligram(mg) administered every 2 weeks (Q2W) up to 8 weeks added to lipid modifying therapy (LMT).

    Reporting group title
    Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg
    Reporting group description
    Subjects with body weight greater than or equal to (>=) 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT.

    Reporting group title
    Cohort 2 - Alirocumab 40 mg Q2W: <50 kg
    Reporting group description
    Subjects with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT.

    Reporting group title
    Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg
    Reporting group description
    Subjects with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT.

    Reporting group title
    Cohort 3 - Alirocumab 75 mg Q4W: <50 kg
    Reporting group description
    Subjects with body weight < 50 kg received SC injection of alirocumab 75 mg administered every 4 weeks (Q4W) up to 8 weeks added to LMT.

    Reporting group title
    Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg
    Reporting group description
    Subjects with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT.

    Reporting group title
    Cohort 4 - Alirocumab 150 mg Q4W: <50 kg
    Reporting group description
    Subjects with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT.

    Reporting group title
    Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Reporting group description
    Subjects with body weight >=50 kg received SC injection of Alirocumab 300 mg administered Q4W up to 12 weeks added to LMT.

    Reporting group values
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg Total
    Number of subjects
    4 6 4 6 6 5 6 5 42
    Age categorical
    Units: subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    11.0 ± 2.0 13.8 ± 2.7 11.3 ± 2.2 14.3 ± 2.3 9.8 ± 1.9 13.8 ± 1.6 11.3 ± 2.2 13.6 ± 2.1 -
    Gender categorical
    Units: subjects
        Female
    2 4 2 2 3 3 1 2 19
        Male
    2 2 2 4 3 2 5 3 23
    Race
    Units: Subjects
        Black or African American
    0 0 0 0 0 0 0 2 2
        White
    0 0 0 0 1 0 0 0 1
        Black or African American/White
    4 6 4 6 5 5 6 3 39
    Low Density Lipoprotrein Cholesterol (LDL-C)
    Units: mmol/L
        arithmetic mean (standard deviation)
    5.169 ± 0.736 4.339 ± 1.200 3.596 ± 0.630 4.510 ± 1.052 4.337 ± 1.147 4.642 ± 1.272 5.100 ± 1.136 4.641 ± 0.926 -

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg
    Reporting group description
    Subjects with body weight less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 30 milligram(mg) administered every 2 weeks (Q2W) up to 8 weeks added to lipid modifying therapy (LMT).

    Reporting group title
    Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg
    Reporting group description
    Subjects with body weight greater than or equal to (>=) 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT.

    Reporting group title
    Cohort 2 - Alirocumab 40 mg Q2W: <50 kg
    Reporting group description
    Subjects with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT.

    Reporting group title
    Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg
    Reporting group description
    Subjects with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT.

    Reporting group title
    Cohort 3 - Alirocumab 75 mg Q4W: <50 kg
    Reporting group description
    Subjects with body weight < 50 kg received SC injection of alirocumab 75 mg administered every 4 weeks (Q4W) up to 8 weeks added to LMT.

    Reporting group title
    Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg
    Reporting group description
    Subjects with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT.

    Reporting group title
    Cohort 4 - Alirocumab 150 mg Q4W: <50 kg
    Reporting group description
    Subjects with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT.

    Reporting group title
    Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Reporting group description
    Subjects with body weight >=50 kg received SC injection of Alirocumab 300 mg administered Q4W up to 12 weeks added to LMT.
    Reporting group title
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg
    Reporting group description
    Period 1: Subjects with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W up to 8 weeks added to LMT. Period 2: Subjects with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W from Week 16 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still < 50 kg, subjects received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg subjects received SC injection of alirocumab 75 mg administered Q2W until Week 130.

    Reporting group title
    Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg
    Reporting group description
    Period 1: Subjects with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. Period 2: Subjects with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W from Week 16 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130.

    Reporting group title
    Cohort 2 - Alirocumab 40 mg Q2W: <50 kg
    Reporting group description
    Period 1: Subjects with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. Period 2: Subjects with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W from Week 16 until switch of dosage in Cohorts 1 and 3. If body weight was still < 50 kg, subjects continued to receive SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg subjects received SC injection of alirocumab 75 mg administered Q2W until Week 130.

    Reporting group title
    Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg
    Reporting group description
    Period 1: Subjects with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. Period 2: Subjects with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W from Week 16 until Week 130.

    Reporting group title
    Cohort 3 - Alirocumab 75 mg Q4W: <50 kg
    Reporting group description
    Period 1: Subjects with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W up to 8 weeks added to LMT. Period 2: Subjects with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W from Week 14 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still < 50 kg, subjects received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg subjects received SC injection of alirocumab 75 mg administered Q2W until Week 130.

    Reporting group title
    Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg
    Reporting group description
    Period 1: Subjects with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. Period 2: Subjects with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 14 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130.

    Reporting group title
    Cohort 4 - Alirocumab 150 mg Q4W: <50 kg
    Reporting group description
    Period 1: Subjects with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. Period 2: Subjects with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 12 until Week 48.

    Reporting group title
    Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Reporting group description
    Period 1: Subjects with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. Period 2: Subjects with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W from Week 12 until Week 48.

    Primary: Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8

    Close Top of page
    End point title
    Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 [1]
    End point description
    Percent change in calculated LDL-C was defined as 100*(calculated LDL-C value at Week 8 - calculated LDL-C value at baseline)/calculated LDL-C value at baseline. All available baseline & post-baseline calculated LDL-C value during OLDFI efficacy treatment period & within 1 of the analysis windows upto Week 8 were used in model. OLDFI efficacy treatment period: period from first investigational medicinal product (IMP) injection to last OLDFI IMP injection + 21 days(for Cohorts 1 & 2) or +35 days (for Cohorts 3 & 4). Adjusted Least-squares (LS) mean & standard error (SE) at Week 8 were obtained from mixed-effect model with repeated measures (MMRM) analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point & dose/dose regimen-by-time point interaction. Modified intent-to-treat (mITT)population included all subjects who received at least 1 dose or partial dose of IMP injection & had an evaluable endpoint during open-label dose finding efficacy treatment period.
    End point type
    Primary
    End point timeframe
    Baseline, Week 8
    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: As the endpoint is descriptive in nature, no statistical analysis is provided.
    End point values
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Number of subjects analysed
    4
    6
    4
    6
    6
    5
    6
    5
    Units: percent change
        least squares mean (standard error)
    -41.1 ± 12.6
    -7.9 ± 10.3
    -40.6 ± 13.2
    -49.8 ± 10.6
    -17.5 ± 10.3
    4.0 ± 11.2
    -31.9 ± 10.3
    -59.8 ± 11.2
    No statistical analyses for this end point

    Secondary: Absolute Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 8

    Close Top of page
    End point title
    Absolute Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 8
    End point description
    Absolute change in LDL-C was calculated by subtracting baseline value from Week 8 value. Adjusted LS means and SE were obtained using MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. Analysis was performed on mITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    End point values
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Number of subjects analysed
    4
    6
    4
    6
    6
    5
    6
    5
    Units: milligram per deciliter (mg/dL)
        least squares mean (standard error)
    -83.7 ± 19.5
    -27.6 ± 15.9
    -55.5 ± 20.8
    -88.3 ± 16.5
    -32.4 ± 15.9
    0.1 ± 17.4
    -55.9 ± 15.9
    -104.3 ± 17.4
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Achieving Calculated Low Density Lipoprotein Cholesterol <130 mg/dL (3.37 mmol/L) at Week 8

    Close Top of page
    End point title
    Percentage of Subjects Achieving Calculated Low Density Lipoprotein Cholesterol <130 mg/dL (3.37 mmol/L) at Week 8
    End point description
    Combined estimate for percentage of subjects was obtained by averaging out all the imputed percentage of subjects reaching the level of interest. A two-step multiple imputation procedure was used to address missing values in the mITT population in the two steps respectively; with number of imputations = 1000. In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables. Analysis was performed on mITT population.
    End point type
    Secondary
    End point timeframe
    At Week 8
    End point values
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Number of subjects analysed
    4
    6
    4
    6
    6
    5
    6
    5
    Units: percentage of subjects
        number (not applicable)
    100.0
    33.3
    97.6
    83.0
    33.3
    20.0
    66.7
    80.0
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Achieving Calculated Low Density Lipoprotein Cholesterol <110 mg/dL (2.84 mmol/L) at Week 8

    Close Top of page
    End point title
    Percentage of Subjects Achieving Calculated Low Density Lipoprotein Cholesterol <110 mg/dL (2.84 mmol/L) at Week 8
    End point description
    Combined estimate for percentage of subjects was obtained by averaging out all the imputed percentage of subjects reaching the level of interest. A two-step multiple imputation procedure was used to address missing values in the mITT population in the two steps respectively; with number of imputations = 1000. In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables. Analysis was performed on mITT population.
    End point type
    Secondary
    End point timeframe
    At Week 8
    End point values
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Number of subjects analysed
    4
    6
    4
    6
    6
    5
    6
    5
    Units: percentage of subjects
        number (not applicable)
    0.0
    0.0
    93.4
    65.7
    16.7
    20.0
    66.7
    80.0
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 12: Cohort 4

    Close Top of page
    End point title
    Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 12: Cohort 4 [2]
    End point description
    Adjusted LS means and SE at Week 12 were obtained from MMRM analysis, with fixed categorical effects of Alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. Analysis was performed on mITT population. Data for this endpoint was planned to be collected for Cohort 4 only.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be collected for Cohort 4 only.
    End point values
    Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Number of subjects analysed
    6
    5
    Units: percent change
        least squares mean (standard error)
    -29.7 ± 6.9
    -49.2 ± 7.5
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in Apolipoprotein (Apo) B at Week 8

    Close Top of page
    End point title
    Percent Change From Baseline in Apolipoprotein (Apo) B at Week 8
    End point description
    Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. Analysis was performed on mITT population. Here, number of subjects analysed=subjects with available data for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    End point values
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Number of subjects analysed
    3
    6
    3
    6
    6
    5
    6
    5
    Units: percent change
        least squares mean (standard error)
    -38.4 ± 12.8
    -9.7 ± 9.1
    -36.4 ± 12.8
    -40.1 ± 9.9
    -12.6 ± 9.1
    -0.9 ± 9.9
    -27.2 ± 9.1
    -51.4 ± 9.9
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 8

    Close Top of page
    End point title
    Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 8
    End point description
    Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose group, time point and dose-by-time point interaction. All available baselines value and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. Analysis was performed on mITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    End point values
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Number of subjects analysed
    4
    6
    4
    6
    6
    5
    6
    5
    Units: percent change
        least squares mean (standard error)
    -39.6 ± 11.9
    -7.1 ± 9.7
    -39.7 ± 12.5
    -43.9 ± 10.0
    -14.4 ± 9.7
    3.2 ± 10.7
    -31.5 ± 9.7
    -54.6 ± 10.7
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in Total Cholesterol (Total-C) at Week 8

    Close Top of page
    End point title
    Percent Change From Baseline in Total Cholesterol (Total-C) at Week 8
    End point description
    Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose group, time point and dose-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. Analysis was performed on mITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    End point values
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Number of subjects analysed
    4
    6
    4
    6
    6
    5
    6
    5
    Units: percent change
        least squares mean (standard error)
    -29.0 ± 9.7
    -4.1 ± 7.9
    -28.6 ± 10.1
    -34.2 ± 8.1
    -10.7 ± 7.9
    5.2 ± 8.6
    -24.0 ± 7.9
    -41.8 ± 8.6
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in Lipoprotein (a) at Week 8

    Close Top of page
    End point title
    Percent Change From Baseline in Lipoprotein (a) at Week 8
    End point description
    Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose group. A two-step multiple imputation procedure was used to address missing values in the mITT population in the two steps respectively (with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables. Analysis was performed on mITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    End point values
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Number of subjects analysed
    4
    6
    4
    6
    6
    5
    6
    5
    Units: percent change
        least squares mean (standard error)
    4.5 ± 21.1
    -26.9 ± 11.6
    1.5 ± 15.1
    -25.2 ± 14.4
    2.2 ± 10.5
    -7.7 ± 11.4
    0.1 ± 10.2
    -7.7 ± 11.1
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in Fasting Triglyceride (TG) at Week 8

    Close Top of page
    End point title
    Percent Change From Baseline in Fasting Triglyceride (TG) at Week 8
    End point description
    Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose group. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables. Analysis was performed on mITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    End point values
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Number of subjects analysed
    4
    6
    4
    6
    6
    5
    6
    5
    Units: percent change
        least squares mean (standard error)
    -0.4 ± 19.6
    -4.0 ± 16.0
    -7.4 ± 28.4
    -14.5 ± 19.0
    19.3 ± 16.0
    -3.1 ± 17.5
    -32.1 ± 16.0
    -7.1 ± 17.5
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 8

    Close Top of page
    End point title
    Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 8
    End point description
    Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen group, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. Analysis was performed on mITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    End point values
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Number of subjects analysed
    4
    6
    4
    6
    6
    5
    6
    5
    Units: percent change
        least squares mean (standard error)
    9.7 ± 7.1
    16.5 ± 5.8
    14.7 ± 7.7
    10.6 ± 6.1
    5.2 ± 5.8
    13.8 ± 6.4
    4.5 ± 5.8
    2.8 ± 6.4
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 8

    Close Top of page
    End point title
    Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 8
    End point description
    Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen group, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. Analysis was performed on mITT population. Here, number of subjects analysed=subjects with available data for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    End point values
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Number of subjects analysed
    3
    6
    3
    5
    6
    5
    6
    5
    Units: percent change
        least squares mean (standard error)
    4.4 ± 7.2
    14.8 ± 5.1
    10.7 ± 7.2
    1.8 ± 5.6
    8.9 ± 5.1
    7.4 ± 5.6
    5.8 ± 5.1
    7.2 ± 5.6
    No statistical analyses for this end point

    Secondary: Absolute Change From Baseline in Apolipoprotein B at Week 8

    Close Top of page
    End point title
    Absolute Change From Baseline in Apolipoprotein B at Week 8
    End point description
    Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose group, time point and dose-by-time point interaction. All available baseline value and a post-baseline value in at least one of the analysis windows up to Week 8 were used in the model. Analysis was performed on mITT population. Here, number of subjects analysed=subjects with available data for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    End point values
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Number of subjects analysed
    3
    6
    3
    5
    6
    5
    6
    5
    Units: mg/dL
        least squares mean (standard error)
    -51.7 ± 15.8
    -18.5 ± 11.1
    -35.3 ± 15.8
    -53.4 ± 12.2
    -15.3 ± 11.1
    -5.4 ± 12.2
    -34.2 ± 11.1
    -63.5 ± 12.2
    No statistical analyses for this end point

    Secondary: Absolute Change From Baseline in Non-High-Density Lipoprotein (Non-HDL-C) at Week 8

    Close Top of page
    End point title
    Absolute Change From Baseline in Non-High-Density Lipoprotein (Non-HDL-C) at Week 8
    End point description
    Adjusted LS means and standard error at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. Analysis was performed on mITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    End point values
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Number of subjects analysed
    4
    6
    4
    6
    6
    5
    6
    5
    Units: mg/dL
        least squares mean (standard error)
    -86.1 ± 20.8
    -28.7 ± 17.0
    -62.7 ± 22.1
    -88.5 ± 17.6
    -29.5 ± 17.0
    -0.6 ± 18.6
    -63.1 ± 17.0
    -106.4 ± 18.6
    No statistical analyses for this end point

    Secondary: Absolute Change From Baseline in Total Cholesterol (Total-C) at Week 8

    Close Top of page
    End point title
    Absolute Change From Baseline in Total Cholesterol (Total-C) at Week 8
    End point description
    Adjusted LS means and standard error at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. Analysis was performed on mITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    End point values
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Number of subjects analysed
    4
    6
    4
    6
    6
    5
    6
    5
    Units: mg/dL
        least squares mean (standard error)
    -80.1 ± 21.4
    -20.8 ± 17.5
    -57.1 ± 22.8
    -84.4 ± 18.1
    27.2 ± 17.5
    5.3 ± 19.1
    -60.7 ± 17.5
    -105.1 ± 19.1
    No statistical analyses for this end point

    Secondary: Absolute Change From Baseline in Lipoprotein (a) at Week 8

    Close Top of page
    End point title
    Absolute Change From Baseline in Lipoprotein (a) at Week 8
    End point description
    Combined estimates and standard errors (SE) were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen group. A two-step multiple imputation procedure was used to address missing values in the mITT population in the two steps respectively (with number of imputations= 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables. Analysis was performed on mITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    End point values
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Number of subjects analysed
    4
    6
    4
    6
    6
    5
    6
    5
    Units: gram/Litre (g/L)
        least squares mean (standard error)
    0.003 ± 0.022
    -0.021 ± 0.017
    0.007 ± 0.073
    -0.025 ± 0.020
    0.023 ± 0.018
    -0.031 ± 0.019
    -0.002 ± 0.017
    -0.120 ± 0.020
    No statistical analyses for this end point

    Secondary: Absolute Change From Baseline in High Density Lipoprotein Cholesterol at Week 8

    Close Top of page
    End point title
    Absolute Change From Baseline in High Density Lipoprotein Cholesterol at Week 8
    End point description
    Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. Analysis was performed on mITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    End point values
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Number of subjects analysed
    4
    6
    4
    6
    6
    5
    6
    5
    Units: mg/dL
        least squares mean (standard error)
    5.9 ± 3.4
    7.7 ± 2.8
    5.5 ± 3.7
    4.9 ± 2.9
    2.4 ± 2.8
    5.9 ± 3.1
    2.2 ± 2.8
    1.2 ± 3.1
    No statistical analyses for this end point

    Secondary: Absolute Change From Baseline in Fasting Triglyceride at Week 8

    Close Top of page
    End point title
    Absolute Change From Baseline in Fasting Triglyceride at Week 8
    End point description
    Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose group. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables. Analysis was performed on mITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    End point values
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Number of subjects analysed
    4
    6
    4
    6
    6
    5
    6
    5
    Units: mmol/L
        least squares mean (standard error)
    -0.121 ± 0.193
    -0.076 ± 0.157
    0.168 ± 0.226
    0.111 ± 0.188
    0.117 ± 0.157
    -0.045 ± 0.172
    -0.402 ± 0.157
    -0.107 ± 0.172
    No statistical analyses for this end point

    Secondary: Absolute Change From Baseline in Apolipoprotein A-1 at Week 8

    Close Top of page
    End point title
    Absolute Change From Baseline in Apolipoprotein A-1 at Week 8
    End point description
    Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. Analysis was performed on mITT population. Here, number of subjects analysed=subjects with available data for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    End point values
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Number of subjects analysed
    3
    6
    3
    5
    6
    5
    6
    5
    Units: mg/dL
        least squares mean (standard error)
    4.0 ± 9.3
    17.7 ± 6.5
    11.3 ± 9.3
    -0.4 ± 7.2
    10.5 ± 6.5
    8.0 ± 7.2
    7.5 ± 6.5
    11.0 ± 7.2
    No statistical analyses for this end point

    Secondary: Absolute Change From Baseline in Ratio Apolipoprotein B/Apolipoprotein A-1 at Week 8

    Close Top of page
    End point title
    Absolute Change From Baseline in Ratio Apolipoprotein B/Apolipoprotein A-1 at Week 8
    End point description
    Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. Analysis was performed on mITT population. Here, number of subjects analysed=subjects with available data for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    End point values
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Number of subjects analysed
    3
    6
    3
    5
    6
    5
    6
    5
    Units: ratio (Apo B/Apo A-1)
        least squares mean (standard error)
    -0.363 ± 0.123
    -0.262 ± 0.087
    -0.370 ± 0.123
    -0.402 ± 0.096
    -0.190 ± 0.087
    -0.086 ± 0.096
    -0.282 ± 0.087
    -0.473 ± 0.096
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    All Adverse Events (AEs) were collected from the time of first dose of investigational medicinal product (IMP) up to the end of study (Week 152) regardless of seriousness or relationship to investigational product.
    Adverse event reporting additional description
    Subjects from Cohorts 1, 2 and 3 had an option to switch to cohort 2 dosage according to their weight category. 7 subjects from Cohort 1 and 11 subjects from Cohort 2 and 3 switched the dosage. Safety population included population who actually received at least one dose or part of a dose of the open-label IMP.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    21.1
    Reporting groups
    Reporting group title
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg
    Reporting group description
    Subjects with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W up to the switch of dosage added to LMT.

    Reporting group title
    Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg
    Reporting group description
    Subjects with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W up to the switch of dosage added to LMT.

    Reporting group title
    Cohort 2 - Alirocumab 40 mg Q2W: <50 kg
    Reporting group description
    Subjects with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to the switch of dosage added to LMT.

    Reporting group title
    Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg
    Reporting group description
    Subjects with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to the switch of dosage added to LMT.

    Reporting group title
    Cohort 3 - Alirocumab 75 mg Q4W: <50 kg
    Reporting group description
    Subjects with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W up to the switch of dosage added to LMT.

    Reporting group title
    Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg
    Reporting group description
    Subjects with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to the switch of dosage added to LMT.

    Reporting group title
    Cohort 4 - Alirocumab 150 mg Q4W: <50 kg
    Reporting group description
    Subjects with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to the end of the OLE period (up to 130 weeks) added to LMT.

    Reporting group title
    Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
    Reporting group description
    Subjects with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to the end of the OLE period (up to 130 weeks) added to LMT.

    Reporting group title
    Alirocumab 40 Q2W Post-switch
    Reporting group description
    Subjects with body weight < 50 kg from cohort 1, 2 and 3 switched to dosage and received SC injection of alirocumab 40 mg administered Q2W from the switch up to the end of the OLE period (up to 130 weeks) added to LMT.

    Reporting group title
    Alirocumab 75 Q2W Post-switch
    Reporting group description
    Subjects from Cohort 1 (7 subjects), Cohort 2 and Cohort 3 (11 subjects) switched to dosage and received SC injection of alirocumab 75 mg administered Q2W up to the end of the OLE period (up to 130 weeks) added to LMT.

    Serious adverse events
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg Alirocumab 40 Q2W Post-switch Alirocumab 75 Q2W Post-switch
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg Alirocumab 40 Q2W Post-switch Alirocumab 75 Q2W Post-switch
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    4 / 4 (100.00%)
    5 / 6 (83.33%)
    1 / 4 (25.00%)
    4 / 6 (66.67%)
    5 / 6 (83.33%)
    3 / 5 (60.00%)
    3 / 6 (50.00%)
    4 / 5 (80.00%)
    7 / 10 (70.00%)
    9 / 18 (50.00%)
    Vascular disorders
    Pallor
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Pyogenic Granuloma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Immune system disorders
    Food Allergy
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Influenza Like Illness
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 10 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    4
    0
    0
    0
    0
    0
    1
    2
    0
    Injection Site Reaction
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    2
    0
    0
    Psychiatric disorders
    Alcohol Abuse
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Anxiety Disorder
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Depressed Mood
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Reproductive system and breast disorders
    Premenstrual Pain
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Animal Scratch
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Arthropod Bite
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Concussion
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Fall
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    1
    0
    0
    1
    0
    0
    0
    0
    0
    Hand Fracture
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Ligament Sprain
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    2 / 18 (11.11%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    0
    0
    2
    Post-Traumatic Pain
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Radius Fracture
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Road Traffic Accident
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Traumatic Haematoma
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Investigations
    Blood Follicle Stimulating Hormone Decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Blood Luteinising Hormone Decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Low Density Lipoprotein Decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Epistaxis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Oropharyngeal Pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Sinus Congestion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Neutropenia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    0
    0
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 10 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    2
    0
    Hypoaesthesia
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Presyncope
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Syncope
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Thoracic Outlet Syndrome
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Eye disorders
    Excessive Eye Blinking
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Gastrointestinal disorders
    Abdominal Discomfort
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Abdominal Pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Constipation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Diarrhoea
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    2
    0
    0
    1
    0
    1
    1
    0
    0
    Nausea
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    Toothache
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Vomiting
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Flank Pain
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Muscle Spasms
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Myalgia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Tendon Pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Metabolism and nutrition disorders
    Type 1 Diabetes Mellitus
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Vitamin D Deficiency
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 10 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    1
    1
    0
    Infections and infestations
    Abscess Limb
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Cystitis Bacterial
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Cytomegalovirus Hepatitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Ear Infection
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 10 (10.00%)
    1 / 18 (5.56%)
         occurrences all number
    1
    0
    0
    1
    1
    0
    0
    0
    1
    1
    Gastroenteritis Viral
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    3 / 10 (30.00%)
    1 / 18 (5.56%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    3
    2
    Infectious Mononucleosis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 6 (33.33%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 10 (10.00%)
    2 / 18 (11.11%)
         occurrences all number
    1
    5
    0
    1
    0
    1
    0
    0
    2
    2
    Otitis Externa
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 10 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    Otitis Media
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    Pharyngitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Pharyngitis Streptococcal
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Post Procedural Infection
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Pyelonephritis
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Sinusitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Tonsillitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Upper Respiratory Tract Infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 10 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    2
    1
    2
    0
    1
    1
    0
    Urinary Tract Infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Varicella
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 10 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Viral Upper Respiratory Tract Infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Vulvovaginal Mycotic Infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 Aug 2016
    Following amendments were made: - Clarifications regarding statin dosing requirements. - Replacement of a 2-option screening period, each of different lengths, with a single, up to 6-week (+1 week), screening period for all subjects, to allow inclusion as soon as eligibility was confirmed. - Clarification related to genotyping performed to confirm a diagnosis of heFH only. - Referral to an eye specialist in case of visual problems concomitant with very low LDL-C levels. Modifications related to approval of protocol amendments to include approval by Health Agencies. - Addition of a recommendation for providing sexual counseling. - Modifications of the levels of certain laboratory values used to define an abnormality requiring additional actions for this pediatric population (neutropenia, thrombocytopenia, acute renal failure, and suspicion of rhabdomyolysis). - Addition of use of clinical judgment in performing follow-up testing, in light of the constraints on amount of blood that could be drawn in the pediatric population.
    11 Dec 2017
    - Addition of a cohort (Cohort 4) using Q4W dosing regimen, evaluating doses of 150 mg for body weight <50 kg and 300 mg for body weight >=50 kg. - Clarification regarding the last alirocumab injection planned during the OLE period.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

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