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    Clinical Trial Results:
    An Open-Label Long-Term Extension to the Randomized, Double-blind, Placebo-controlled, Multi-center, Cross-over Study of Rosuvastatin in Children and Adolescents (aged 6 to <18 years) with Homozygous Familial Hypercholesterolemia (HoFH)

    Summary
    EudraCT number
    		 2014-004746-99
    Trial protocol
    		 BE   SE   DK  
    Global end of trial date
    21 Mar 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    07 May 2017
    First version publication date
    07 May 2017
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    D365NC00001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AstraZeneca AB
    Sponsor organisation address
    AstraZeneca Global Regulatory Affairs, Södertälje, Sweden, S-15185
    Public contact
    Information Centre, AstraZeneca, information.center@astrazeneca.com
    Scientific contact
    Information Centre, AstraZeneca, information.center@astrazeneca.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    08 Mar 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    17 Nov 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Mar 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The safety objective of the study was to assess the long-term safety and tolerability of rosuvastatin 20 mg in pediatric patients with HoFH. The efficacy objective of the study was to assess the longitudinal profile of rosuvastatin 20 mg on lipid parameters (LDL-C, high-density lipoprotein cholesterol [HDL-C], TC, triglycerides [TG], non-HDL-C, LDL-C/HDL-C, TC/HDL-C, non-HDL-C/HDL-C, apolipoprotein A-1 [ApoA-1], and ApoB/ApoA-1). The PK objective of the study was to characterize the trough plasma exposure of rosuvastatin in pediatric patients with HoFH who were up-titrated to a daily dose of rosuvastatin 40 mg.
    Protection of trial subjects
    Yada yada
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    06 Jun 2015
    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
    Belgium: 1
    Country: Number of subjects enrolled
    Canada: 1
    Country: Number of subjects enrolled
    Israel: 3
    Country: Number of subjects enrolled
    Malaysia: 1
    Country: Number of subjects enrolled
    Denmark: 1
    Country: Number of subjects enrolled
    Taiwan: 2
    Worldwide total number of subjects
    9
    EEA total number of subjects
    2
    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)
    5
    Adolescents (12-17 years)
    4
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The nine (9) patients recruited were all participants in the D3561C00004 HYDRA study

    Pre-assignment
    Screening details
    		 Inclusion criterion was to having completed D3561C00004

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Overall
    Arm description
    		 All patients
    Arm type
    		 Long term extension

    Investigational medicinal product name
    Rosuvastatin 20mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    20mg daily

    Investigational medicinal product name
    Rosuvastatin 40mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    20mg daily

    Number of subjects in period 1
    		Overall
    Started
    9
    Completed
    4
    Not completed
    5
         Started on non-allowed con med
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall
    Reporting group description
    		 All patients

    Reporting group values
    		 Overall Total
    Number of subjects
    		 9 9
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 6 6
        Adolescents (12-17 years)
    		 3 3
        Adults (18-64 years)
    		 0 0
        From 65-84 years
    		 0 0
        85 years and over
    		 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 10.6 ( 2.83 ) -
    Gender, Male/Female
    Units: Subjects
        Female
    		 4 4
        Male
    		 5 5
    Subject analysis sets

    Subject analysis set title
    Full analysis set
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Full analysis set, comprised of patient who received at least one dose of study drug.

    Subject analysis set title
    Sequence A
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Rosuva/Placebo in the D3561C00004 cross-over phase

    Subject analysis set title
    Sequence B
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Placebo/Rosuva in the D3561C00004 cross-over phase

    Subject analysis sets values
    		 Full analysis set Sequence A Sequence B
    Number of subjects
    9
    4
    5
    Age categorical
    Units: Subjects
        In utero
    0
    0
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
    0
    0
        Newborns (0-27 days)
    0
    0
    0
        Infants and toddlers (28 days-23 months)
    0
    0
    0
        Children (2-11 years)
    6
    2
    4
        Adolescents (12-17 years)
    3
    2
    1
        Adults (18-64 years)
    0
    0
    0
        From 65-84 years
    0
    0
    0
        85 years and over
    0
    0
    0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    10.6 ( 2.83 )
    10.8 ( 3.86 )
    10.4 ( 2.19 )
    Gender, Male/Female
    Units: Subjects
        Female
    4
    2
    2
        Male
    5
    2
    3

    End points

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    End points reporting groups
    Reporting group title
    Overall
    Reporting group description
    		 All patients

    Subject analysis set title
    Full analysis set
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Full analysis set, comprised of patient who received at least one dose of study drug.

    Subject analysis set title
    Sequence A
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Rosuva/Placebo in the D3561C00004 cross-over phase

    Subject analysis set title
    Sequence B
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Placebo/Rosuva in the D3561C00004 cross-over phase

    Primary: Safety and tolerability in terms of frequency and severity of adverse events, Serious Adverse Events

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    End point title
    		 Safety and tolerability in terms of frequency and severity of adverse events, Serious Adverse Events [1]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Full analysis set
    Number of subjects analysed
    9
    Units: participants
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of frequency and severity of adverse events, Discontinuations due to Adverse Events

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    End point title
    		 Safety and tolerability in terms of frequency and severity of adverse events, Discontinuations due to Adverse Events [2]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [2] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Full analysis set
    Number of subjects analysed
    9
    Units: participants
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Basophils/Leukocytes (%) >ULN

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    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Basophils/Leukocytes (%) >ULN [3]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [3] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    0
    0
        Week 6
    0
    0
        Week 12
    0
    0
        Week 18
    0
    0
        Week 24
    0
    0
        Week 36
    0
    0
        Week 48
    0
    0
        Week 60
    1
    0
        Week 72
    0
    0
        Week 84
    0
    0
        Week 96
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of growth, height

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    End point title
    		 Safety and tolerability in terms of growth, height [4]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [4] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: cm
    arithmetic mean (standard deviation)
        Baseline
    142.5 ( 23.57 )
    136.8 ( 15.02 )
        Week 6
    143.5 ( 23.57 )
    136.8 ( 15.32 )
        Week 12
    144 ( 23.9 )
    137.6 ( 14.94 )
        Week 18
    145.3 ( 23.56 )
    138 ( 14.83 )
        Week 24
    145.8 ( 24.02 )
    139.2 ( 15.74 )
        Week 36
    147 ( 24.15 )
    140.6 ( 15.61 )
        Week 48
    148.8 ( 24.25 )
    142.2 ( 15.21 )
        Week 60
    158 ( 19.47 )
    144 ( 16.37 )
        Week 72
    159 ( 20.22 )
    145 ( 15.12 )
        Week 84
    159.7 ( 20.43 )
    148.3 ( 17.27 )
        Week 96
    165 ( 25.46 )
    138 ( 12.73 )
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormalitites in sexual maturation

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    End point title
    		 Safety and tolerability in terms of abnormalitites in sexual maturation [5]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [5] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Full analysis set
    Number of subjects analysed
    9
    Units: participants
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of growth, height SD-score

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    End point title
    		 Safety and tolerability in terms of growth, height SD-score [6]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [6] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: standard deviations
    arithmetic mean (standard deviation)
        Baseline
    -0.43 ( 2.025 )
    -1.05 ( 1.787 )
        Week 6
    -0.48 ( 1.911 )
    -1.05 ( 1.871 )
        Week 12
    -0.41 ( 1.975 )
    -1.19 ( 1.709 )
        Week 18
    -0.43 ( 1.61 )
    -1.14 ( 1.705 )
        Week 24
    -0.6 ( 1.73 )
    -0.96 ( 1.67 )
        Week 36
    -0.43 ( 1.836 )
    -0.76 ( 1.727 )
        Week 48
    -0.16 ( 1.781 )
    -0.72 ( 1.729 )
        Week 60
    0.05 ( 1.757 )
    -1.04 ( 1.604 )
        Week 72
    0 ( 1.635 )
    -0.87 ( 1.604 )
        Week 84
    0.08 ( 1.734 )
    -0.33 ( 1.627 )
        Week 96
    1.18 ( 0.436 )
    -0.51 ( 0.886 )
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of growth, weight

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    End point title
    		 Safety and tolerability in terms of growth, weight [7]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [7] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: kg
    arithmetic mean (standard deviation)
        Baseline
    36.25 ( 14.719 )
    37.42 ( 16.089 )
        Week 6
    37.2 ( 16.23 )
    38.02 ( 16.7 )
        Week 12
    37.93 ( 17.11 )
    38.16 ( 17.501 )
        Week 18
    38.85 ( 17.633 )
    38.4 ( 16.688 )
        Week 24
    39.15 ( 17.521 )
    39 ( 16.704 )
        Week 36
    39.98 ( 18.293 )
    39.88 ( 15.015 )
        Week 48
    41 ( 17.579 )
    41.16 ( 16.045 )
        Week 60
    48.47 ( 16.933 )
    41.8 ( 15.656 )
        Week 72
    48.43 ( 16.393 )
    42.1 ( 17.047 )
        Week 84
    50.17 ( 16.737 )
    45.28 ( 19.143 )
        Week 96
    57.35 ( 16.476 )
    33.55 ( 2.192 )
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Alanine Aminotransferase (U/L) >ULN

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    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Alanine Aminotransferase (U/L) >ULN [8]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [8] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    0
    0
        Week 6
    0
    0
        Week 12
    0
    1
        Week 18
    0
    1
        Week 24
    0
    0
        Week 36
    0
    1
        Week 48
    0
    1
        Week 60
    0
    1
        Week 72
    0
    1
        Week 84
    0
    0
        Week 96
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Albumin (g/dL) >ULN

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    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Albumin (g/dL) >ULN [9]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [9] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    0
    1
        Week 6
    0
    0
        Week 12
    0
    0
        Week 18
    0
    1
        Week 24
    0
    0
        Week 36
    0
    0
        Week 48
    0
    0
        Week 60
    0
    0
        Week 72
    0
    0
        Week 84
    0
    0
        Week 96
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Aspartate Aminotransferase (U/L) >ULN

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    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Aspartate Aminotransferase (U/L) >ULN [10]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [10] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    0
    0
        Week 6
    0
    0
        Week 12
    0
    0
        Week 18
    0
    0
        Week 24
    0
    0
        Week 36
    0
    0
        Week 48
    0
    0
        Week 60
    0
    1
        Week 72
    0
    0
        Week 84
    0
    0
        Week 96
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Bicarbonate (mol/L) <LLN

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    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Bicarbonate (mol/L) <LLN [11]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [11] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    0
    0
        Week 6
    0
    1
        Week 12
    1
    1
        Week 18
    0
    1
        Week 24
    1
    1
        Week 36
    1
    2
        Week 48
    1
    1
        Week 60
    1
    3
        Week 72
    2
    1
        Week 84
    1
    1
        Week 96
    0
    1
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Bicarbonate (mol/L) >ULN

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    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Bicarbonate (mol/L) >ULN [12]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [12] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    0
    0
        Week 6
    0
    0
        Week 12
    0
    0
        Week 18
    0
    0
        Week 24
    0
    0
        Week 36
    0
    0
        Week 48
    0
    0
        Week 60
    0
    0
        Week 72
    0
    1
        Week 84
    0
    0
        Week 96
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Ery. Mean Corpuscular HGB Concentration (g/dL) <LLN

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    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Ery. Mean Corpuscular HGB Concentration (g/dL) <LLN [13]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [13] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    2
    3
        Week 6
    0
    2
        Week 12
    2
    2
        Week 18
    1
    2
        Week 24
    2
    3
        Week 36
    1
    3
        Week 48
    1
    4
        Week 60
    1
    4
        Week 72
    2
    3
        Week 84
    2
    3
        Week 96
    0
    1
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Ery. Mean Corpuscular HGB (pg) <LLN

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    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Ery. Mean Corpuscular HGB (pg) <LLN [14]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [14] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    1
    3
        Week 6
    1
    2
        Week 12
    1
    2
        Week 18
    1
    2
        Week 24
    1
    2
        Week 36
    1
    2
        Week 48
    1
    3
        Week 60
    0
    3
        Week 72
    0
    3
        Week 84
    0
    3
        Week 96
    2
    1
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Ery. Mean Corpuscular Volume (fL) <LLN

    		 Close Top of page
    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Ery. Mean Corpuscular Volume (fL) <LLN [15]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [15] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    1
    2
        Week 6
    1
    2
        Week 12
    1
    2
        Week 18
    1
    2
        Week 24
    1
    2
        Week 36
    1
    2
        Week 48
    1
    2
        Week 60
    0
    2
        Week 72
    0
    3
        Week 84
    0
    3
        Week 96
    2
    1
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Ery. Mean Corpuscular Volume (fL) >ULN

    		 Close Top of page
    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Ery. Mean Corpuscular Volume (fL) >ULN [16]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [16] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    0
    0
        Week 6
    0
    0
        Week 12
    0
    0
        Week 18
    0
    0
        Week 24
    0
    0
        Week 36
    0
    0
        Week 48
    0
    0
        Week 60
    0
    0
        Week 72
    0
    0
        Week 84
    1
    0
        Week 96
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Erythrocytes (10^12/L) <LLN

    		 Close Top of page
    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Erythrocytes (10^12/L) <LLN [17]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [17] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    1
    0
        Week 6
    0
    0
        Week 12
    0
    1
        Week 18
    0
    1
        Week 24
    0
    0
        Week 36
    0
    1
        Week 48
    0
    0
        Week 60
    0
    0
        Week 72
    0
    1
        Week 84
    0
    0
        Week 96
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Erythrocytes (10^12/L) >ULN

    		 Close Top of page
    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Erythrocytes (10^12/L) >ULN [18]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [18] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    0
    1
        Week 6
    0
    0
        Week 12
    0
    1
        Week 18
    0
    0
        Week 24
    1
    2
        Week 36
    0
    2
        Week 48
    0
    1
        Week 60
    0
    1
        Week 72
    0
    2
        Week 84
    0
    1
        Week 96
    0
    1
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Hematocrit (%) <LLN

    		 Close Top of page
    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Hematocrit (%) <LLN [19]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [19] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    2
    2
        Week 6
    2
    3
        Week 12
    1
    2
        Week 18
    1
    3
        Week 24
    0
    1
        Week 36
    1
    1
        Week 48
    0
    2
        Week 60
    0
    2
        Week 72
    0
    1
        Week 84
    0
    1
        Week 96
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Hemoglobin (g/dL) <LLN

    		 Close Top of page
    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Hemoglobin (g/dL) <LLN [20]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [20] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    2
    3
        Week 6
    2
    3
        Week 12
    1
    3
        Week 18
    1
    3
        Week 24
    0
    2
        Week 36
    1
    3
        Week 48
    1
    3
        Week 60
    0
    3
        Week 72
    0
    3
        Week 84
    0
    3
        Week 96
    0
    1
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Leukocytes >ULN

    		 Close Top of page
    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Leukocytes >ULN [21]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [21] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    0
    0
        Week 6
    0
    0
        Week 12
    0
    0
        Week 18
    0
    0
        Week 24
    0
    0
        Week 36
    0
    0
        Week 48
    0
    1
        Week 60
    0
    0
        Week 72
    0
    0
        Week 84
    0
    0
        Week 96
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Lymphocytes/Leukocytes (%) <LLN

    		 Close Top of page
    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Lymphocytes/Leukocytes (%) <LLN [22]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [22] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    0
    0
        Week 6
    0
    0
        Week 12
    0
    0
        Week 18
    0
    0
        Week 24
    0
    0
        Week 36
    0
    0
        Week 48
    0
    1
        Week 60
    0
    0
        Week 72
    0
    0
        Week 84
    0
    0
        Week 96
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Lymphocytes/Leukocytes (%) >ULN

    		 Close Top of page
    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Lymphocytes/Leukocytes (%) >ULN [23]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [23] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    0
    1
        Week 6
    0
    1
        Week 12
    0
    1
        Week 18
    0
    1
        Week 24
    0
    1
        Week 36
    0
    1
        Week 48
    0
    1
        Week 60
    0
    1
        Week 72
    0
    0
        Week 84
    0
    0
        Week 96
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Monocytes/Leukocytes (%) >ULN

    		 Close Top of page
    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Monocytes/Leukocytes (%) >ULN [24]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [24] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    0
    0
        Week 6
    0
    0
        Week 12
    0
    0
        Week 18
    0
    0
        Week 24
    0
    0
        Week 36
    0
    1
        Week 48
    0
    0
        Week 60
    0
    0
        Week 72
    0
    0
        Week 84
    0
    0
        Week 96
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Platelets (10^9/L) >ULN

    		 Close Top of page
    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Platelets (10^9/L) >ULN [25]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [25] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    1
    0
        Week 6
    0
    1
        Week 12
    0
    0
        Week 18
    0
    0
        Week 24
    0
    1
        Week 36
    0
    0
        Week 48
    0
    0
        Week 60
    0
    0
        Week 72
    0
    1
        Week 84
    0
    0
        Week 96
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Blood Urea Nitrogen (mg/dL) <LLN

    		 Close Top of page
    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Blood Urea Nitrogen (mg/dL) <LLN [26]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [26] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    1
    0
        Week 6
    1
    0
        Week 12
    1
    0
        Week 18
    1
    0
        Week 24
    0
    0
        Week 36
    0
    1
        Week 48
    1
    0
        Week 60
    0
    0
        Week 72
    0
    0
        Week 84
    0
    0
        Week 96
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Chloride (mmol/L) >ULN

    		 Close Top of page
    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Chloride (mmol/L) >ULN [27]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [27] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    0
    1
        Week 6
    0
    1
        Week 12
    0
    0
        Week 18
    0
    1
        Week 24
    0
    0
        Week 36
    0
    1
        Week 48
    0
    0
        Week 60
    0
    1
        Week 72
    0
    1
        Week 84
    0
    0
        Week 96
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Creatine Kinase (U/L) >ULN

    		 Close Top of page
    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Creatine Kinase (U/L) >ULN [28]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [28] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    0
    0
        Week 6
    1
    0
        Week 12
    0
    0
        Week 18
    0
    0
        Week 24
    1
    0
        Week 36
    1
    0
        Week 48
    0
    0
        Week 60
    1
    0
        Week 72
    0
    0
        Week 84
    0
    0
        Week 96
    1
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Glucose (mg/dL) >ULN

    		 Close Top of page
    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Glucose (mg/dL) >ULN [29]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [29] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    0
    0
        Week 6
    0
    0
        Week 12
    0
    0
        Week 18
    0
    1
        Week 24
    0
    0
        Week 36
    0
    0
        Week 48
    0
    0
        Week 60
    0
    0
        Week 72
    0
    0
        Week 84
    0
    1
        Week 96
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Lactate Dehydrogenase (U/L) <LLN

    		 Close Top of page
    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Lactate Dehydrogenase (U/L) <LLN [30]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [30] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    0
    0
        Week 6
    0
    0
        Week 12
    0
    0
        Week 18
    0
    0
        Week 24
    0
    0
        Week 36
    0
    0
        Week 48
    0
    0
        Week 60
    0
    0
        Week 72
    0
    1
        Week 84
    0
    0
        Week 96
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Phosphate (mg/dL) >ULN

    		 Close Top of page
    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Phosphate (mg/dL) >ULN [31]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [31] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    0
    0
        Week 6
    0
    0
        Week 12
    0
    0
        Week 18
    0
    1
        Week 24
    0
    0
        Week 36
    0
    0
        Week 48
    0
    0
        Week 60
    0
    0
        Week 72
    0
    1
        Week 84
    0
    1
        Week 96
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Protein (g/dL) >ULN

    		 Close Top of page
    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Protein (g/dL) >ULN [32]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [32] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    0
    0
        Week 6
    0
    0
        Week 12
    0
    1
        Week 18
    0
    0
        Week 24
    0
    1
        Week 36
    1
    0
        Week 48
    0
    0
        Week 60
    0
    0
        Week 72
    0
    0
        Week 84
    0
    0
        Week 96
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Sodium (mmol/L) <LLN

    		 Close Top of page
    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Sodium (mmol/L) <LLN [33]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [33] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    2
    0
        Week 6
    1
    0
        Week 12
    0
    0
        Week 18
    3
    1
        Week 24
    0
    1
        Week 36
    0
    0
        Week 48
    0
    1
        Week 60
    0
    0
        Week 72
    0
    1
        Week 84
    0
    0
        Week 96
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal serum laboratory values, Urate (mg/dL) >ULN

    		 Close Top of page
    End point title
    		 Safety and tolerability in terms of abnormal serum laboratory values, Urate (mg/dL) >ULN [34]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [34] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    1
    0
        Week 6
    1
    1
        Week 12
    1
    0
        Week 18
    1
    1
        Week 24
    1
    1
        Week 36
    1
    1
        Week 48
    1
    1
        Week 60
    1
    1
        Week 72
    1
    1
        Week 84
    1
    1
        Week 96
    1
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal urine laboratory values, Urine Ketones

    		 Close Top of page
    End point title
    		 Safety and tolerability in terms of abnormal urine laboratory values, Urine Ketones [35]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [35] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    0
    0
        Week 6
    0
    0
        Week 12
    0
    0
        Week 18
    0
    1
        Week 24
    0
    0
        Week 36
    0
    0
        Week 48
    0
    1
        Week 60
    0
    0
        Week 72
    0
    0
        Week 84
    0
    0
        Week 96
    1
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal urine laboratory values, Urine Occult Blood

    		 Close Top of page
    End point title
    		 Safety and tolerability in terms of abnormal urine laboratory values, Urine Occult Blood [36]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [36] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    1
    1
        Week 6
    2
    1
        Week 12
    1
    2
        Week 18
    1
    1
        Week 24
    1
    1
        Week 36
    1
    1
        Week 48
    1
    1
        Week 60
    1
    1
        Week 72
    2
    1
        Week 84
    1
    1
        Week 96
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal urine laboratory values, Urine Protein

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    End point title
    		 Safety and tolerability in terms of abnormal urine laboratory values, Urine Protein [37]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [37] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    2
    1
        Week 6
    1
    1
        Week 12
    2
    1
        Week 18
    1
    0
        Week 24
    2
    1
        Week 36
    2
    0
        Week 48
    1
    1
        Week 60
    3
    1
        Week 72
    3
    1
        Week 84
    2
    1
        Week 96
    1
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal ECG, abnormalities

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    End point title
    		 Safety and tolerability in terms of abnormal ECG, abnormalities [38]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [38] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    0
    0
        Week 24
    0
    0
        Final Visit
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal physical exams, Cardiovascular

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    End point title
    		 Safety and tolerability in terms of abnormal physical exams, Cardiovascular [39]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [39] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    0
    0
        Week 6
    0
    0
        Week 12
    0
    0
        Week 18
    0
    0
        Week 24
    0
    0
        Week 36
    0
    1
        Week 48
    0
    1
        Week 60
    0
    1
        Week 72
    0
    1
        Week 84
    0
    0
        Week 96
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal physical exams, General Appearance

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    End point title
    		 Safety and tolerability in terms of abnormal physical exams, General Appearance [40]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [40] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    1
    2
        Week 6
    1
    2
        Week 12
    1
    2
        Week 18
    1
    2
        Week 24
    1
    2
        Week 36
    1
    2
        Week 48
    1
    2
        Week 60
    1
    2
        Week 72
    1
    2
        Week 84
    1
    2
        Week 96
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal physical exams, Head and Neck

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    End point title
    		 Safety and tolerability in terms of abnormal physical exams, Head and Neck [41]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [41] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    0
    1
        Week 6
    0
    1
        Week 12
    0
    1
        Week 18
    0
    1
        Week 24
    0
    1
        Week 36
    0
    1
        Week 48
    0
    1
        Week 60
    0
    1
        Week 72
    0
    1
        Week 84
    0
    0
        Week 96
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal physical exams, Musculoskeletal/Extremities

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    End point title
    		 Safety and tolerability in terms of abnormal physical exams, Musculoskeletal/Extremities [42]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [42] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    0
    0
        Week 6
    0
    0
        Week 12
    0
    0
        Week 18
    0
    0
        Week 24
    0
    0
        Week 36
    0
    0
        Week 48
    0
    1
        Week 60
    0
    0
        Week 72
    0
    0
        Week 84
    0
    0
        Week 96
    0
    0
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal physical exams, Skin

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    End point title
    		 Safety and tolerability in terms of abnormal physical exams, Skin [43]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [43] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    3
    2
        Week 6
    3
    2
        Week 12
    3
    2
        Week 18
    3
    2
        Week 24
    3
    2
        Week 36
    3
    2
        Week 48
    3
    2
        Week 60
    2
    2
        Week 72
    2
    2
        Week 84
    2
    1
        Week 96
    2
    1
    No statistical analyses for this end point

    Primary: Safety and tolerability in terms of abnormal vital signs

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    End point title
    		 Safety and tolerability in terms of abnormal vital signs [44]
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks
    Notes
    [44] - 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: There are no statistical analyses entered for primary endpoints. No formal hypothesis testing or analyses were done for safety endpoints.
    End point values
    		 Sequence A Sequence B
    Number of subjects analysed
    4
    5
    Units: participants
        Baseline
    0
    0
        Week 6
    0
    0
        Week 12
    0
    0
        Week 18
    0
    0
        Week 24
    0
    0
        Week 36
    0
    0
        Week 48
    0
    0
        Week 60
    0
    0
        Week 72
    0
    0
        Week 84
    0
    0
        Week 96
    0
    0
    No statistical analyses for this end point

    Secondary: Percent change in LDL-C from end of placebo of D3561C00005 to the end of D356NC00001, repeated measures analysis

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    End point title
    		 Percent change in LDL-C from end of placebo of D3561C00005 to the end of D356NC00001, repeated measures analysis
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 22 months
    End point values
    		 Full analysis set
    Number of subjects analysed
    9
    Units: % LDL-C
    geometric mean (confidence interval 95%)
        Visit 1
    -21 (-32.1 to -8)
        Visit 2
    -18.6 (-28.4 to -7.4)
        Visit 3
    -14.7 (-25.2 to -2.8)
        Visit 4
    -12.1 (-23.8 to 1.4)
        Visit 5
    -21.3 (-33.7 to -6.6)
        Visit 6
    -20.5 (-33.6 to -4.8)
        Visit 7
    -12.4 (-28.2 to 7)
    No statistical analyses for this end point

    Secondary: Percent change in HDL-C from end of placebo of D3561C00005 to the end of D356NC00001, repeated measures analysis

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    End point title
    		 Percent change in HDL-C from end of placebo of D3561C00005 to the end of D356NC00001, repeated measures analysis
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 22 months
    End point values
    		 Full analysis set
    Number of subjects analysed
    9
    Units: % HDL-C
    geometric mean (confidence interval 95%)
        Visit 1
    12.3 (1.3 to 24.5)
        Visit 2
    19 (6.2 to 33.4)
        Visit 3
    5.2 (-8.4 to 20.8)
        Visit 4
    4.4 (-10.8 to 22.2)
        Visit 5
    4.4 (-12.7 to 24.9)
        Visit 6
    9.4 (-9.4 to 32.1)
        Visit 7
    3.8 (-13.1 to 23.9)
    No statistical analyses for this end point

    Secondary: Percent change in Total Cholesterol (TC) from end of placebo of D3561C00005 to the end of D356NC00001, repeated measures analysis

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    End point title
    		 Percent change in Total Cholesterol (TC) from end of placebo of D3561C00005 to the end of D356NC00001, repeated measures analysis
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 22 months
    End point values
    		 Full analysis set
    Number of subjects analysed
    9
    Units: % TC
    geometric mean (confidence interval 95%)
        Visit 1
    -19.4 (-29.7 to -7.6)
        Visit 2
    -16.8 (-25.7 to -6.8)
        Visit 3
    -14 (-23.6 to -3.3)
        Visit 4
    -11.8 (-22.3 to 0.1)
        Visit 5
    -19.9 (-31.1 to -6.9)
        Visit 6
    -18.3 (-30.2 to -4.3)
        Visit 7
    -11.9 (-26.3 to 5.2)
    No statistical analyses for this end point

    Secondary: Percent change in Triglycerides (TG) from end of placebo of D3561C00005 to the end of D356NC00001, repeated measures analysis

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    End point title
    		 Percent change in Triglycerides (TG) from end of placebo of D3561C00005 to the end of D356NC00001, repeated measures analysis
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 22 months
    End point values
    		 Full analysis set
    Number of subjects analysed
    9
    Units: % TG
    geometric mean (confidence interval 95%)
        Visit 1
    -17.3 (-31.9 to 0.5)
        Visit 2
    -17.4 (-34.2 to 3.8)
        Visit 3
    -16.2 (-36.1 to 10.1)
        Visit 4
    -22 (-42.8 to 6.5)
        Visit 5
    -23.3 (-45 to 7.1)
        Visit 6
    -21.7 (-43.4 to 8.4)
        Visit 7
    -28.5 (-47 to -3.6)
    No statistical analyses for this end point

    Secondary: Percent change in Non-HDL-C from end of placebo of D3561C00005 to the end of D356NC00001, repeated measures analysis

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    End point title
    		 Percent change in Non-HDL-C from end of placebo of D3561C00005 to the end of D356NC00001, repeated measures analysis
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 22 months
    End point values
    		 Full analysis set
    Number of subjects analysed
    9
    Units: % Non-HDL-C
    geometric mean (confidence interval 95%)
        Visit 1
    -21.7 (-32.7 to -9)
        Visit 2
    -19.2 (-28.8 to -8.3)
        Visit 3
    -15.7 (-25.7 to -4.3)
        Visit 4
    -13.3 (-24.3 to -0.7)
        Visit 5
    -22.1 (-33.8 to -8.4)
        Visit 6
    -21 (-33.2 to -6.5)
        Visit 7
    -13.2 (-28.1 to 4.8)
    No statistical analyses for this end point

    Secondary: Percent change in LDL-C/HDL-C from end of placebo of D3561C00005 to the end of D356NC00001, repeated measures analysis

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    End point title
    		 Percent change in LDL-C/HDL-C from end of placebo of D3561C00005 to the end of D356NC00001, repeated measures analysis
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 22 months
    End point values
    		 Full analysis set
    Number of subjects analysed
    9
    Units: % LDL-C/HDL-C
    geometric mean (confidence interval 95%)
        Visit 1
    -39.4 (-51.6 to -24.1)
        Visit 2
    -41.2 (-52.8 to -26.9)
        Visit 3
    -36.1 (-48.8 to -20.2)
        Visit 4
    -35 (-49.5 to -16.4)
        Visit 5
    -48.6 (-61.3 to -31.7)
        Visit 6
    -42.2 (-57.2 to -21.9)
        Visit 7
    -27.8 (-47.4 to -0.9)
    No statistical analyses for this end point

    Secondary: Percent change in TC/HDL-C from end of placebo of D3561C00005 to the end of D356NC00001, repeated measures analysis

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    End point title
    		 Percent change in TC/HDL-C from end of placebo of D3561C00005 to the end of D356NC00001, repeated measures analysis
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 22 months
    End point values
    		 Full analysis set
    Number of subjects analysed
    9
    Units: % TC/HDL-C
    geometric mean (confidence interval 95%)
        Visit 1
    -30.6 (-38.3 to -21.9)
        Visit 2
    -29.4 (-38.5 to -18.9)
        Visit 3
    -20.5 (-32 to -7)
        Visit 4
    -16.6 (-30.7 to 0.4)
        Visit 5
    -24.1 (-38.6 to -6.2)
        Visit 6
    -29.2 (-43.2 to -11.7)
        Visit 7
    -15.6 (-33.7 to 7.5)
    No statistical analyses for this end point

    Secondary: Percent change in Non-HDL-C/HDL-C from end of placebo of D3561C00005 to the end of D356NC00001, repeated measures analysis

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    End point title
    		 Percent change in Non-HDL-C/HDL-C from end of placebo of D3561C00005 to the end of D356NC00001, repeated measures analysis
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 22 months
    End point values
    		 Full analysis set
    Number of subjects analysed
    9
    Units: % Non-HDL-C/HDL-C
    geometric mean (confidence interval 95%)
        Visit 1
    -32.9 (-41.2 to -23.3)
        Visit 2
    -31.5 (-41.2 to -20.3)
        Visit 3
    -22.3 (-34.3 to -8.1)
        Visit 4
    -18.1 (-32.8 to -0.3)
        Visit 5
    -26.3 (-41.3 to -7.4)
        Visit 6
    -31.8 (-46 to -13.9)
        Visit 7
    -17.6 (-36.2 to 6.5)
    No statistical analyses for this end point

    Secondary: Percent change in ApoB from end of placebo of D3561C00005 to the end of D356NC00001, repeated measures analysis

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    End point title
    		 Percent change in ApoB from end of placebo of D3561C00005 to the end of D356NC00001, repeated measures analysis
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 22 months
    End point values
    		 Full analysis set
    Number of subjects analysed
    9
    Units: % ApoB
    geometric mean (confidence interval 95%)
        Visit 1
    -20.5 (-29.8 to -9.9)
        Visit 2
    -18.7 (-26.7 to -9.8)
        Visit 3
    -15.2 (-23.9 to -5.6)
        Visit 4
    -10.5 (-20.4 to 0.5)
        Visit 5
    -17.2 (-27.9 to -4.9)
        Visit 6
    -19.2 (-30.2 to -6.5)
        Visit 7
    -9.5 (-23.5 to 7.2)
    No statistical analyses for this end point

    Secondary: Percent change in ApoA-1 from end of placebo of D3561C00005 to the end of D356NC00001, repeated measures analysis

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    End point title
    		 Percent change in ApoA-1 from end of placebo of D3561C00005 to the end of D356NC00001, repeated measures analysis
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 22 months
    End point values
    		 Full analysis set
    Number of subjects analysed
    9
    Units: % ApoA-1
    geometric mean (confidence interval 95%)
        Visit 1
    8 (0 to 16.6)
        Visit 2
    7 (-2.3 to 17.1)
        Visit 3
    5.3 (-4.9 to 16.7)
        Visit 4
    6.5 (-5.3 to 19.7)
        Visit 5
    1 (-11.5 to 15.3)
        Visit 6
    10.7 (-2.6 to 25.7)
        Visit 7
    1.6 (-12.9 to 18.4)
    No statistical analyses for this end point

    Secondary: Percent change in ApoB/ApoA-1 from end of placebo of D3561C00005 to the end of D356NC00001, repeated measures analysis

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    End point title
    		 Percent change in ApoB/ApoA-1 from end of placebo of D3561C00005 to the end of D356NC00001, repeated measures analysis
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 22 months
    End point values
    		 Full analysis set
    Number of subjects analysed
    9
    Units: % ApoB/ApoA-1
    geometric mean (confidence interval 95%)
        Visit 1
    -23.3 (-34.3 to -10.5)
        Visit 2
    -22.1 (-32.7 to -9.8)
        Visit 3
    -18.9 (-31.2 to -4.4)
        Visit 4
    -15.7 (-30.2 to 1.7)
        Visit 5
    -17 (-33.1 to 2.8)
        Visit 6
    -26 (-41.1 to -7)
        Visit 7
    -14.7 (-33.7 to 9.7)
    No statistical analyses for this end point

    Secondary: Pharmacokinetic profile in terms of trough concentrations in pediatric HoFH taking a daily dose of rosuvastatin 40mg

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    End point title
    		 Pharmacokinetic profile in terms of trough concentrations in pediatric HoFH taking a daily dose of rosuvastatin 40mg
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 22 months
    End point values
    		 Full analysis set
    Number of subjects analysed
    9
    Units: ng/mL
    number (not applicable)
        Day 292
    9
        Day 376
    7.14
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    72 weeks
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Overall
    Reporting group description
    		 All patients

    Serious adverse events
    		 Overall
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 9 (0.00%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 Overall
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    5 / 9 (55.56%)
    Injury, poisoning and procedural complications
    Ligament sprain
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    General disorders and administration site conditions
    Chest discomfort
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Reproductive system and breast disorders
    Dysmenorrhoea
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Proteinuria
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Psychiatric disorders
    Attention deficit/hyperactivity disorder
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences all number
    2
    Otitis externa
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

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

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