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    Clinical Trial Results:
    A Multi-Site, Open-Label Extension Trial of Oral RPC1063 in Relapsing Multiple Sclerosis

    Summary
    EudraCT number
    		 2015-002500-91
    Trial protocol
    		 HU   BE   GB   ES   BG   SK   GR   PL   LV   EE   LT   PT   SE   HR   IT  
    Global end of trial date
    05 Jan 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    28 Dec 2023
    First version publication date
    28 Dec 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    RPC01-3001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02576717
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Bristol-Myers Squibb
    Sponsor organisation address
    Chaussee de la Hulpe 185, Brussels, Belgium, 1170
    Public contact
    EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com
    Scientific contact
    Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.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
    30 Mar 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Jan 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To characterize the long-term safety and tolerability of RPC1063 in patients with relapsing multiple sclerosis
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial participants were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    16 Oct 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
    Belarus: 203
    Country: Number of subjects enrolled
    Belgium: 12
    Country: Number of subjects enrolled
    Bosnia and Herzegovina: 16
    Country: Number of subjects enrolled
    Bulgaria: 43
    Country: Number of subjects enrolled
    Croatia: 32
    Country: Number of subjects enrolled
    Estonia: 10
    Country: Number of subjects enrolled
    Georgia: 82
    Country: Number of subjects enrolled
    Germany: 7
    Country: Number of subjects enrolled
    Greece: 11
    Country: Number of subjects enrolled
    Hungary: 21
    Country: Number of subjects enrolled
    Italy: 22
    Country: Number of subjects enrolled
    Latvia: 6
    Country: Number of subjects enrolled
    Lithuania: 4
    Country: Number of subjects enrolled
    Moldova, Republic of: 12
    Country: Number of subjects enrolled
    New Zealand: 7
    Country: Number of subjects enrolled
    Poland: 676
    Country: Number of subjects enrolled
    Portugal: 23
    Country: Number of subjects enrolled
    Romania: 57
    Country: Number of subjects enrolled
    Russian Federation: 364
    Country: Number of subjects enrolled
    Serbia: 177
    Country: Number of subjects enrolled
    Slovakia: 5
    Country: Number of subjects enrolled
    South Africa: 16
    Country: Number of subjects enrolled
    Spain: 57
    Country: Number of subjects enrolled
    Sweden: 2
    Country: Number of subjects enrolled
    Ukraine: 538
    Country: Number of subjects enrolled
    United Kingdom: 10
    Country: Number of subjects enrolled
    United States: 81
    Worldwide total number of subjects
    2494
    EEA total number of subjects
    988
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    2494
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants must have participated in Trial RPC01-201, Trial RPC01-301, and/or Trial RPC01-1001 prior to joining RPC01-3001.

    Pre-assignment
    Screening details
    		 Participants were Pooled According to Treatment Group Assignment in Parent Trial.

    Period 1
    Period 1 title
    Treatment Period: Safety Population (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Parent Treatment Group IFN-B-1a 30 ug
    Arm description
    		 Participants received a 7-day titration regimen of RPC1063, as applicable to reach the targeted dose of 1.0 mg which was taken by mouth once per day until the end of the trial or until the Sponsor discontinued the development program. Participants were instructed to take RPC1063 at approximately the same time each day with or without food.
    Arm type
    		 Experimental

    Investigational medicinal product name
    RPC1063
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    1 mg daily by mouth

    Arm title
    		 Parent Treatment Group: RPC1063 0.5 mg
    Arm description
    		 Participants received a 7-day titration regimen of RPC1063, as applicable to reach the targeted dose of 1.0 mg which was taken by mouth once per day until the end of the trial or until the Sponsor discontinued the development program. Participants were instructed to take RPC1063 at approximately the same time each day with or without food.
    Arm type
    		 Experimental

    Investigational medicinal product name
    RPC1063
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    1 mg daily by mouth

    Arm title
    		 Parent Treatment Group: RPC1063 1.0 mg
    Arm description
    		 Participants received a 7-day titration regimen of RPC1063, as applicable to reach the targeted dose of 1.0 mg which was taken by mouth once per day until the end of the trial or until the Sponsor discontinued the development program. Participants were instructed to take RPC1063 at approximately the same time each day with or without food.
    Arm type
    		 Experimental

    Investigational medicinal product name
    RPC1063
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    1 mg daily by mouth

    Number of subjects in period 1
    		Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Started
    736
    877
    881
    Transferred from IFN β-1a
    0 [1]
    3 [2]
    1 [3]
    Transferred from RPC1063 0.5 mg
    0 [4]
    0 [5]
    1 [6]
    From equivalent Placebo group
    0 [7]
    37 [8]
    35 [9]
    Completed
    562
    692
    696
    Not completed
    174
    185
    185
         Adverse event, serious fatal
    3
    5
    3
         Physician decision
    3
    8
    9
         Covid-19 Pandemic
    -
    1
    1
         Other Reasons
    14
    18
    16
         Adverse event, non-fatal
    26
    32
    26
         Sponsor Decision
    -
    -
    1
         Lost to follow-up
    9
    10
    19
         Participant Voluntarily Withdrew from Study
    91
    83
    85
         Protocol deviation
    4
    -
    5
         Lack of efficacy
    24
    28
    20
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Participants did not transfer from another group.
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Participants did not transfer from another group.
    [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Participants transferred from another group.
    [4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Participants did not transfer from another group.
    [5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Participants transferred from another group.
    [6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Participants transferred from another group.
    [7] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Participants did not transfer from another group.
    [8] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Participants transferred from another group.
    [9] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Participants transferred from another group.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Parent Treatment Group IFN-B-1a 30 ug
    Reporting group description
    		 Participants received a 7-day titration regimen of RPC1063, as applicable to reach the targeted dose of 1.0 mg which was taken by mouth once per day until the end of the trial or until the Sponsor discontinued the development program. Participants were instructed to take RPC1063 at approximately the same time each day with or without food.

    Reporting group title
    Parent Treatment Group: RPC1063 0.5 mg
    Reporting group description
    		 Participants received a 7-day titration regimen of RPC1063, as applicable to reach the targeted dose of 1.0 mg which was taken by mouth once per day until the end of the trial or until the Sponsor discontinued the development program. Participants were instructed to take RPC1063 at approximately the same time each day with or without food.

    Reporting group title
    Parent Treatment Group: RPC1063 1.0 mg
    Reporting group description
    		 Participants received a 7-day titration regimen of RPC1063, as applicable to reach the targeted dose of 1.0 mg which was taken by mouth once per day until the end of the trial or until the Sponsor discontinued the development program. Participants were instructed to take RPC1063 at approximately the same time each day with or without food.

    Reporting group values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg Total
    Number of subjects
    		 736 877 881 2494
    Age Categorical
    Units: Participants
        <=18 years
    		 0 0 0 0
        Between 18 and 65 years
    		 736 877 881 2494
        >=65 years
    		 0 0 0 0
    Sex: Female, Male
    Units: Participants
        Female
    		 498 595 575 1668
        Male
    		 238 282 306 826
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 3 8 16 27
        Not Hispanic or Latino
    		 733 869 865 2467
        Unknown or Not Reported
    		 0 0 0 0
    Race/Ethnicity, Customized
    Race
    Units: Subjects
        White
    		 734 865 875 2474
        Black or African American
    		 1 7 6 14
        Asian
    		 0 3 0 3
        Other
    		 1 2 0 3

    End points

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    End points reporting groups
    Reporting group title
    Parent Treatment Group IFN-B-1a 30 ug
    Reporting group description
    		 Participants received a 7-day titration regimen of RPC1063, as applicable to reach the targeted dose of 1.0 mg which was taken by mouth once per day until the end of the trial or until the Sponsor discontinued the development program. Participants were instructed to take RPC1063 at approximately the same time each day with or without food.

    Reporting group title
    Parent Treatment Group: RPC1063 0.5 mg
    Reporting group description
    		 Participants received a 7-day titration regimen of RPC1063, as applicable to reach the targeted dose of 1.0 mg which was taken by mouth once per day until the end of the trial or until the Sponsor discontinued the development program. Participants were instructed to take RPC1063 at approximately the same time each day with or without food.

    Reporting group title
    Parent Treatment Group: RPC1063 1.0 mg
    Reporting group description
    		 Participants received a 7-day titration regimen of RPC1063, as applicable to reach the targeted dose of 1.0 mg which was taken by mouth once per day until the end of the trial or until the Sponsor discontinued the development program. Participants were instructed to take RPC1063 at approximately the same time each day with or without food.

    Subject analysis set title
    Parent Treatment Group IFN-B-1a 30 ug ITT Population
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Participants received a 7-day titration regimen of RPC1063, as applicable to reach the targeted dose of 1.0 mg which was taken by mouth once per day until the end of the trial or until the Sponsor discontinued the development program. Participants were instructed to take RPC1063 at approximately the same time each day with or without food.

    Subject analysis set title
    Parent Treatment Group: RPC1063 0.5 mg ITT
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Participants received a 7-day titration regimen of RPC1063, as applicable to reach the targeted dose of 1.0 mg which was taken by mouth once per day until the end of the trial or until the Sponsor discontinued the development program. Participants were instructed to take RPC1063 at approximately the same time each day with or without food.

    Subject analysis set title
    Parent Treatment Group: RPC1063 1.0 mg ITT
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Participants received a 7-day titration regimen of RPC1063, as applicable to reach the targeted dose of 1.0 mg which was taken by mouth once per day until the end of the trial or until the Sponsor discontinued the development program. Participants were instructed to take RPC1063 at approximately the same time each day with or without food.

    Subject analysis set title
    Withdrawal Analysis Combination
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received a 7-day titration regimen of RPC1063, as applicable to reach the targeted dose of 1.0 mg which was taken by mouth once per day until the end of the trial or until the Sponsor discontinued the development program. Participants were instructed to take RPC1063 at approximately the same time each day with or without food.

    Subject analysis set title
    Parent Treatment Group: Placebo for RPC1063 0.5 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received a 7-day titration regimen of RPC1063 to reach the targeted dose of 1.0 mg which was taken by mouth once per day until the end of the trial or until the Sponsor discontinued the development program. Participants were instructed to take RPC1063 at approximately the same time each day with or without food.

    Subject analysis set title
    Parent Treatment Group: Placebo for RPC1063 1 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received a 7-day titration regimen of RPC1063 to reach the targeted dose of 1.0 mg which was taken by mouth once per day until the end of the trial or until the Sponsor discontinued the development program. Participants were instructed to take RPC1063 at approximately the same time each day with or without food.

    Primary: Number of Participants Experiencing Adverse Events (AEs)

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    End point title
    		 Number of Participants Experiencing Adverse Events (AEs) [1]
    End point description
    An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the use of medicinal product, whether or not considered related to the investigational medicinal product.
    End point type
    Primary
    End point timeframe
    From first dose to 90-days post last dose (an average of 65 months up to a max of 85 months)
    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: Only descriptive statistics were planned for this endpoint.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Number of subjects analysed
    736
    877
    881
    Units: Participants
    668
    775
    776
    No statistical analyses for this end point

    Primary: Number of Participants Experiencing Serious Adverse Events (SAEs)

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    End point title
    		 Number of Participants Experiencing Serious Adverse Events (SAEs) [2]
    End point description
    A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose results in death, is life-threatening (defined as an event in which the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization.
    End point type
    Primary
    End point timeframe
    From first dose to 90-days post last dose (an average of 65 months up to a max of 85 months)
    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: Only descriptive statistics were planned for this endpoint.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Number of subjects analysed
    736
    877
    881
    Units: Participants
    108
    139
    134
    No statistical analyses for this end point

    Primary: Number of Participants Experiencing Adverse Events (AEs) of Special Interest

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    End point title
    		 Number of Participants Experiencing Adverse Events (AEs) of Special Interest [3]
    End point description
    An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the use of medicinal product, whether or not considered related to the investigational medicinal product.
    End point type
    Primary
    End point timeframe
    From first dose to 90-days post last dose (an average of 65 months up to a max of 85 months)
    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: Only descriptive statistics were planned for this endpoint.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Number of subjects analysed
    736
    877
    881
    Units: Participants
        Infections and infestations
    19
    26
    19
        Neoplasms benign, malignant and unspecified
    9
    14
    16
        Blood and lymphatic system disorders
    0
    0
    1
        Nervous system disorders
    0
    2
    1
        Eye disorders
    5
    2
    2
        Cardiac disorders
    0
    1
    2
        Hepatobiliary disorders
    0
    1
    0
        Skin and subcutaneous tissue disorders
    0
    0
    1
        Congenital, familial and genetic disorders
    1
    0
    0
        Investigations
    15
    14
    8
    No statistical analyses for this end point

    Primary: Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation

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    End point title
    		 Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation [4]
    End point description
    An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the use of medicinal product, whether or not considered related to the investigational medicinal product.
    End point type
    Primary
    End point timeframe
    From first dose to 90-days post last dose (an average of 65 months up to a max of 85 months)
    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: Only descriptive statistics were planned for this endpoint.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Number of subjects analysed
    736
    877
    881
    Units: Participants
    35
    35
    28
    No statistical analyses for this end point

    Primary: Number of Participants Experiencing Adverse Events (AEs) Leading to Withdrawal

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    End point title
    		 Number of Participants Experiencing Adverse Events (AEs) Leading to Withdrawal [5]
    End point description
    An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the use of medicinal product, whether or not considered related to the investigational medicinal product.
    End point type
    Primary
    End point timeframe
    From first dose to 90-days post last dose (an average of 65 months up to a max of 85 months)
    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: Only descriptive statistics were planned for this endpoint.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Number of subjects analysed
    736
    877
    881
    Units: Participants
    32
    35
    28
    No statistical analyses for this end point

    Primary: Number of Participants with Abnormalities in Blood Absolute Lymphocyte Count (ALC)

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    End point title
    		 Number of Participants with Abnormalities in Blood Absolute Lymphocyte Count (ALC) [6]
    End point description
    An absolute lymphocyte count (ALC) is a part of a blood test that measures the number of lymphocytes, a type of white blood cell, in the blood. Lymphocytes help fight infections and diseases. Reductions in ALC levels for participants in this study is expected and is a primary pharmacodynamic effect of RPC1063. LLN = Lower limit of normal
    End point type
    Primary
    End point timeframe
    From first dose up until last dose of study treatment (up to approximately 82 months)
    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: Only descriptive statistics were planned for this endpoint.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Number of subjects analysed
    727
    868
    877
    Units: Participants
        ALC < 0.2 x 10^9/L
    33
    33
    27
        ALC < 0.5 x 10^9/L
    265
    323
    339
        ALC < 0.8 x 10^9/L
    497
    620
    616
        ALC < LLN
    592
    703
    704
    No statistical analyses for this end point

    Primary: Number of Participants with Abnormalities in Blood Absolute Neutrophil Count (ANC)

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    End point title
    		 Number of Participants with Abnormalities in Blood Absolute Neutrophil Count (ANC) [7]
    End point description
    An absolute neutrophil count is a part of a blood test that measures the number of neutrophils, a type of white blood cell, in the blood. Neutrophils help fight infections and diseases.
    End point type
    Primary
    End point timeframe
    From first dose up until last dose of study treatment (up to approximately 82 months)
    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: Only descriptive statistics were planned for this endpoint.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Number of subjects analysed
    727
    868
    877
    Units: Participants
    0
    2
    1
    No statistical analyses for this end point

    Primary: Number of Participants with Abnormalities in White Blood Cell Count (WBC)

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    End point title
    		 Number of Participants with Abnormalities in White Blood Cell Count (WBC) [8]
    End point description
    A white blood cell count is a part of a blood test that measures the number of white blood cells in the blood. White blood cells help fight infections and diseases. LLN = Lower limit of normal
    End point type
    Primary
    End point timeframe
    From first dose up until last dose of study treatment (up to approximately 82 months)
    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: Only descriptive statistics were planned for this endpoint.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Number of subjects analysed
    727
    868
    877
    Units: Participants
        Total WBC > 20 x 10^9/L
    0
    0
    2
        Total WBC < 3 x 10^9/L
    27
    48
    43
        Total WBC < 2 x 10^9/L
    0
    2
    0
        Total WBC < 1 x 10^9/L
    0
    0
    0
        Total WBC < LLN
    92
    107
    108
    No statistical analyses for this end point

    Primary: Number of Participants with Electrocardiogram (ECG) Result Outliers

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    End point title
    		 Number of Participants with Electrocardiogram (ECG) Result Outliers [9]
    End point description
    An electrocardiogram (ECG) measures electrical activity of the heart to detect cardiac problems.
    End point type
    Primary
    End point timeframe
    From first dose to 28-days post last dose (an average of 63 months up to a max of 83 months)
    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: Only descriptive statistics were planned for this endpoint.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Number of subjects analysed
    736
    876
    880
    Units: Participants
        QT > 480 (ms)
    6
    5
    3
        QT > 500 (ms)
    1
    0
    0
        QTcF > 450 (ms)
    44
    49
    44
        QTcF > 480 (ms)
    1
    5
    3
        QTcF > 500 (ms)
    0
    0
    0
        QTcB > 450 (ms)
    173
    186
    184
        QTcB > 480 (ms)
    8
    15
    13
        QTcB > 500 (ms)
    0
    2
    0
        Change from Baseline in QTcF >30 ms
    134
    140
    120
        Change from Baseline in QTcF >60 ms
    0
    5
    6
        Change from Baseline in QTcB >30 ms
    183
    215
    205
        Change from Baseline in QTcB >60 ms
    5
    9
    13
        Atrial Ventricular Bock or Conduction Ratio, 2:1
    0
    0
    1
    No statistical analyses for this end point

    Primary: Number of Participants with Abnormalities in Specific Liver Function Tests

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    End point title
    		 Number of Participants with Abnormalities in Specific Liver Function Tests [10]
    End point description
    The number of participants with laboratory abnormalities in specific liver tests above ULN by category. ULN = Upper Limit of Normal.
    End point type
    Primary
    End point timeframe
    From first dose up until last dose of study treatment (up to approximately 82 months)
    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: Only descriptive statistics were planned for this endpoint.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Number of subjects analysed
    728
    875
    880
    Units: Participants
        > 1 x ULN
    311
    353
    353
        >= 2 x ULN
    90
    100
    107
        >= 3 x ULN
    32
    30
    29
        >= 4 x ULN
    16
    19
    6
        >= 5 x ULN
    8
    12
    0
        >= 10 x ULN
    4
    5
    0
    No statistical analyses for this end point

    Primary: Number of Participants with Clinically Relevant Abnormalities in Vital Signs

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    End point title
    		 Number of Participants with Clinically Relevant Abnormalities in Vital Signs [11]
    End point description
    Vital signs included body temperature, sitting heart rate/pulse (HR), sitting systolic blood pressure (SBP), sitting diastolic blood pressure (DBP).
    End point type
    Primary
    End point timeframe
    At baseline and 60 months after first dose of study therapy
    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: Only descriptive statistics were planned for this endpoint.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Number of subjects analysed
    567
    715
    707
    Units: Participants
        Temp(C) >38.5 and incr frm BL >= 1
    0
    0
    0
        HR(bpm) >120bpm post-BL or incr frm BL>20 bpm
    15
    19
    26
        HR(bpm) >120 bpm post-BL if BL<=120 bpm
    0
    0
    0
        HR(bpm) Incr from BL > 20 bpm
    15
    19
    26
        HR(bpm) <45 bpm post-BL or decr from BL>20bpm
    7
    12
    8
        HR(bpm) <45 bpm post-BL if BL >=45 bpm
    0
    0
    0
        HR(bpm) Decr from BL >20 bpm
    7
    12
    8
        SBP>180 mmHg post-BL or incr from BL>40 mmHg
    3
    5
    5
        SBP >180 mmHg post-BL if BL<=180 mmHg
    0
    0
    0
        SBP: Increase from BL>40 mmHg
    3
    5
    5
        SBP<90 mmHg post-BL or decr from BL>30 mmHg
    3
    1
    3
        SBP<90 mmHg post-BL if BL>=90 mmHg
    1
    0
    0
        SBP: Decr from BL > 30 mmHg
    2
    1
    3
        DBP>105 mmHg post-BL or incr from BL>30 mmHg
    2
    4
    4
        DBP >105 mmHg post-BL if BL<=105 mmHg
    1
    2
    3
        DBP: Increase from BBL>30 mmHg
    1
    2
    2
        DBP<50 mmHg post-BL or decr from BL>30 mmHg
    1
    2
    0
        DBP<50 mmHg post-BL if BL>=50 mmHg
    0
    0
    0
        DBP: Decrease from BL>30 mmHg
    1
    2
    0
    No statistical analyses for this end point

    Primary: Number of Participants with Physical Examination Abnormalities

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    End point title
    		 Number of Participants with Physical Examination Abnormalities [12]
    End point description
    The number of participants with abnormal physical examination results. The assessments included abdominal, extremity, head, heart, lungs, neck, neurological non-MS, other and skin assessments.
    End point type
    Primary
    End point timeframe
    At baseline and every 12 months thereafter up until 84 months post first dose.
    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: Only descriptive statistics were planned for this endpoint.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Number of subjects analysed
    736
    877
    881
    Units: Participants
        Baseline - Abdominal
    0
    0
    1
        Baseline - Extremities
    3
    2
    8
        Baseline - Head
    0
    1
    1
        Baseline - Heart
    1
    0
    1
        Baseline - Lungs
    0
    1
    2
        Baseline - Neck
    0
    1
    3
        Baseline - Neurological-Non-MS
    1
    1
    5
        Baseline - Other
    2
    6
    4
        Baseline - Skin
    17
    17
    16
        Month 12 - Abdominal
    1
    2
    2
        Month 12 - Extremities
    2
    4
    6
        Month 12 - Head
    2
    2
    3
        Month 12 - Heart
    3
    0
    0
        Month 12 - Lungs
    0
    0
    1
        Month 12 - Neck
    0
    1
    3
        Month 12 - Neurological-Non-MS
    1
    3
    0
        Month 12 - Other
    2
    4
    2
        Month 12 - Skin
    25
    24
    21
        Month 24 - Abdominal
    0
    2
    2
        Month 24 -Extremities
    5
    9
    6
        Month 24 - Head
    3
    4
    2
        Month 24 - Lungs
    0
    1
    3
        Month 24 - Neck
    1
    1
    2
        Month 24 - Neurological-Non-MS
    2
    1
    3
        Month 24 - Other
    2
    3
    3
        Month 24 - Skin
    20
    21
    23
        Month 36 - Abdominal
    1
    1
    1
        Month 36 - Extremities
    5
    5
    7
        Month 36 - Head
    1
    0
    4
        Month 36 - Heart
    0
    0
    1
        Month 36 - Lungs
    1
    2
    1
        Month 36 - Neck
    1
    1
    0
        Month 36 - Neurological-Non-MS
    1
    1
    4
        Month 36 - Other
    4
    4
    4
        Month 36 - Skin
    22
    32
    34
        Month 48 - Abdominal
    0
    0
    1
        Month 48 - Extremities
    4
    7
    5
        Month 48 - Head
    1
    2
    1
        Month 48 - Heart
    0
    0
    1
        Month 48 - Lungs
    0
    1
    2
        Month 48 - Neck
    0
    1
    0
        Month 48 - Neurological-Non-MS
    3
    1
    0
        Month 48 - Other
    2
    3
    4
        Month 48 - Skin
    19
    23
    18
        Month 60 - Abdominal
    1
    2
    0
        Month 60 - Extremities
    4
    9
    11
        Month 60 - Head
    1
    1
    1
        Month 60 - Heart
    0
    0
    2
        Month 60 - Lungs
    0
    1
    2
        Month 60 - Neck
    2
    0
    0
        Month 60 - Neurological-Non-MS
    2
    1
    4
        Month 60 - Other
    3
    4
    1
        Month 60 - Skin
    16
    28
    18
        Month 72 - Abdominal
    1
    2
    2
        Month 72 - Extremities
    4
    5
    5
        Month 72 - Head
    0
    1
    1
        Month 72 - Heart
    0
    0
    0
        Month 72 - Lungs
    0
    0
    1
        Month 72 - Neck
    1
    0
    0
        Month 72 - Neurological-Non-MS
    2
    2
    2
        Month 72 - Other
    5
    3
    2
        Month 72 - Skin
    8
    19
    10
        Month 84 - Abdominal
    0
    1
    0
        Month 84 - Extremities
    0
    1
    1
        Month 84 - Skin
    0
    2
    0
    No statistical analyses for this end point

    Primary: Number of Participants Self-Identifying Suicidality by Columbia-Suicide Severity Rating Scale (C-SSRS)

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    End point title
    		 Number of Participants Self-Identifying Suicidality by Columbia-Suicide Severity Rating Scale (C-SSRS) [13]
    End point description
    The Columbia-Suicide Severity Rating Scale (C-SSRS) is a unique suicide risk assessment tool that supports suicide risk assessment through a series of simple, plain-language questions. The answers help users identify whether someone is at risk for suicide, assess the severity and immediacy of that risk, and gauge the level of support that the person needs.
    End point type
    Primary
    End point timeframe
    At baseline and every 3 months thereafter up until 78 months post first dose.
    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: Only descriptive statistics were planned for this endpoint.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Number of subjects analysed
    733
    874
    879
    Units: Participants
        At baseline (Suicidal Ideation or Behavior)
    0
    2
    0
        At month 3 (Suicidal Ideation or Behavior)
    2
    1
    1
        At month 6 (Suicidal Ideation or Behavior)
    1
    1
    2
        At month 9 (Suicidal Ideation or Behavior)
    3
    0
    1
        At month 12 (Suicidal Ideation or Behavior)
    3
    0
    2
        At month 15 (Suicidal Ideation or Behavior)
    0
    0
    1
        At month 18 (Suicidal Ideation or Behavior)
    1
    1
    2
        At month 21 (Suicidal Ideation or Behavior)
    1
    0
    1
        At month 24 (Suicidal Ideation or Behavior)
    1
    2
    1
        At month 27 (Suicidal Ideation or Behavior)
    0
    0
    0
        At month 33 (Suicidal Ideation or Behavior)
    1
    0
    0
        At month 36 (Suicidal Ideation or Behavior)
    2
    1
    0
        At month 39 (Suicidal Ideation or Behavior)
    0
    1
    0
        At month 42 (Suicidal Ideation or Behavior)
    0
    0
    1
        At month 45 (Suicidal Ideation or Behavior)
    0
    0
    0
        At month 48 (Suicidal Ideation or Behavior)
    2
    0
    1
        At month 54 (Suicidal Ideation or Behavior)
    1
    0
    1
        At month 57 (Suicidal Ideation or Behavior)
    0
    0
    0
        At month 60 (Suicidal Ideation or Behavior)
    2
    1
    1
        At month 66 (Suicidal Ideation or Behavior)
    1
    2
    1
        At month 69 (Suicidal Ideation or Behavior)
    1
    0
    1
        At month 72 (Suicidal Ideation or Behavior)
    1
    0
    1
        At month 78 (Suicidal Ideation or Behavior)
    0
    0
    1
    No statistical analyses for this end point

    Primary: Change in Physician's Withdrawal Checklist (PWC-20) Score from Last Day on Treatment

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    End point title
    		 Change in Physician's Withdrawal Checklist (PWC-20) Score from Last Day on Treatment [14]
    End point description
    End point type
    Primary
    End point timeframe
    1, 4, 7, 14, 21, and 90 post last dose.
    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: Only descriptive statistics were planned for this endpoint.
    End point values
    		 Withdrawal Analysis Combination
    Number of subjects analysed
    95
    Units: PWS-20 Score
    arithmetic mean (standard deviation)
        End of Treatment
    -0.1 ± 6.33
        Follow-up Visit Day 1
    -0.6 ± 5.06
        Follow-up Visit Day 4
    -0.5 ± 4.51
        Follow-up Visit Day 7
    -1.1 ± 4.33
        Follow-up Visit Day 14
    -0.4 ± 4.93
        Follow-up Visit Day 21
    -1.2 ± 5.31
        Follow-up Visit Day 90
    -0.7 ± 5.15
    No statistical analyses for this end point

    Primary: Change in Hospital Anxiety and Depression Scale (HADS) Score from Last Day on Treatment

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    End point title
    		 Change in Hospital Anxiety and Depression Scale (HADS) Score from Last Day on Treatment [15]
    End point description
    End point type
    Primary
    End point timeframe
    1, 4, 7, 14, 21, and 90 days post last dose.
    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: Only descriptive statistics were planned for this endpoint.
    End point values
    		 Withdrawal Analysis Combination
    Number of subjects analysed
    96
    Units: HADS Score
    arithmetic mean (standard deviation)
        Depression - End of Treatment
    0.3 ± 3.17
        Depression - Follow-up Visit Day 1
    -0.1 ± 2.15
        Depression - Follow-up Visit Day 4
    -0.1 ± 2.13
        Depression - Follow-up Visit Day 7
    -0.2 ± 2.29
        Depression - Follow-up Visit Day 14
    0.1 ± 2.36
        Depression - Follow-up Visit Day 21
    0.1 ± 2.35
        Depression - 90-Day Safety Follow-up Visit
    -0.2 ± 2.86
        Anxiety - End of Treatment
    -0.3 ± 2.76
        Anxiety - Follow-up Visit Day 1
    -0.5 ± 2.33
        Anxiety - Follow-up Visit Day 4
    -0.4 ± 2.30
        Anxiety - Follow-up Visit Day 7
    -0.8 ± 2.47
        Anxiety - Follow-up Visit Day 14
    -0.6 ± 2.17
        Anxiety - Follow-up Visit Day 21
    -0.7 ± 2.35
        Anxiety -90-Day Safety Follow-up Visit
    -0.7 ± 2.99
    No statistical analyses for this end point

    Primary: Changes in Epworth Sleepiness Scale (ESS) Score from Last Day on Treatment

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    End point title
    		 Changes in Epworth Sleepiness Scale (ESS) Score from Last Day on Treatment [16]
    End point description
    End point type
    Primary
    End point timeframe
    1, 4, 7, 14, 21, and 90 days post last dose.
    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: Only descriptive statistics were planned for this endpoint.
    End point values
    		 Withdrawal Analysis Combination
    Number of subjects analysed
    96
    Units: ESS Score
    arithmetic mean (standard deviation)
        End of Treatment
    0.4 ± 4.92
        Follow-up Visit Day 1
    -0.6 ± 4.28
        Follow-up Visit Day 4
    -0.5 ± 4.38
        Follow-up Visit Day 7
    -0.7 ± 4.25
        Follow-up Visit Day 14
    -0.9 ± 4.10
        Follow-up Visit Day 21
    -0.9 ± 4.42
        Follow-up Visit Day 90
    -0.8 ± 3.75
    No statistical analyses for this end point

    Primary: Changes in Columbia-Suicide Severity Rating Scale (C-SSRS) Score from Last Day on Treatment

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    End point title
    		 Changes in Columbia-Suicide Severity Rating Scale (C-SSRS) Score from Last Day on Treatment [17]
    End point description
    End point type
    Primary
    End point timeframe
    1, 4, 7, 14, 21, and 90 days post last dose.
    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: Only descriptive statistics were planned for this endpoint.
    End point values
    		 Withdrawal Analysis Combination
    Number of subjects analysed
    250
    Units: Participants
        End of Treatment
    3
        Follow-up Visit Day 1
    0
        Follow-up Visit Day 4
    0
        Follow-up Visit Day 7
    0
        Follow-up Visit Day 14
    0
        Follow-up Visit Day 21
    0
        Safety Follow-up Visit (Day 28)
    0
        Follow-up Visit Day 90
    0
    No statistical analyses for this end point

    Primary: Changes in Vital Sign Values from Last Day on Treatment

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    End point title
    		 Changes in Vital Sign Values from Last Day on Treatment [18]
    End point description
    End point type
    Primary
    End point timeframe
    1, 4, 7, 14, 21, and 90 days post last dose.
    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: Only descriptive statistics were planned for this endpoint.
    End point values
    		 Withdrawal Analysis Combination
    Number of subjects analysed
    252
    Units: Unit Specific to Each Measure
    arithmetic mean (standard deviation)
        Systolic Blood Pressure: End of Treatment
    -1.77 ± 11.189
        Systolic Blood Pressure: Follow-up Visit Day 1
    0.63 ± 8.311
        Systolic Blood Pressure: Follow-up Visit Day 4
    -0.04 ± 8.931
        Systolic Blood Pressure: Follow-up Visit Day 7
    0.82 ± 7.911
        Systolic Blood Pressure: Follow-up Visit Day 14
    -0.4 ± 8.128
        Systolic Blood Pressure: Follow-up Visit Day 21
    1.25 ± 9.029
        Systolic Blood Pressure: Safety Follow-up
    -0.72 ± 11.135
        Systolic Blood Pressure: Follow-up Visit Day 90
    -0.69 ± 10.865
        Diastolic Blood Pressure: End of Treatment
    -1.10 ± 8.356
        Diastolic Blood Pressure: Follow-up Visit Day 1
    -1.18 ± 8.218
        Diastolic Blood Pressure: Follow-up Visit Day 4
    -2.02 ± 7.760
        Diastolic Blood Pressure: Follow-up Visit Day 7
    -1.80 ± 7.275
        Diastolic Blood Pressure: Follow-up Visit Day 14
    -1.82 ± 7.643
        Diastolic Blood Pressure: Follow-up Visit Day 21
    -1.00 ± 8.181
        Diastolic Blood Pressure Safety Follow-up
    -1.21 ± 8.103
        Diastolic Blood Pressure: Follow-up Day 90
    -2.01 ± 7.689
    No statistical analyses for this end point

    Secondary: Annualized Relapse Rate (ARR)

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    End point title
    		 Annualized Relapse Rate (ARR)
    End point description
    The Annualized Relapse Rate (ARR) is the average number of relapses per study arm in one year. A relapse is defined as the occurrence of new or worsening neurological symptoms attributable to multiple sclerosis (MS) and immediately preceded by a relatively stable or improving neurological state of at least 30 days. The adjusted ARR was based on the negative binomial regression model with parent treatment group, adjusted for region (Eastern Europe vs Rest of World), age at parent baseline, and the parent baseline number of gadolinium-enhanced (GdE) lesions. The natural log transformation of time on treatment was used as an offset term to adjust for participants having different exposure times.
    End point type
    Secondary
    End point timeframe
    From first dose up until last dose of study treatment or data-cutoff date, whichever occurred first (up to approximately 87 months)
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Number of subjects analysed
    736
    877
    881
    Units: Proportion of participants
        median (confidence interval 95%)
    0.097 (0.078 to 0.121)
    0.108 (0.088 to 0.133)
    0.090 (0.073 to 0.111)
    No statistical analyses for this end point

    Secondary: Time to First Relapse (TFR)

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    End point title
    		 Time to First Relapse (TFR)
    End point description
    The time between first dose of study treatment and first relapse if experienced by a participant. A participant was censored if follow-up ended before a relapse occurred, whether due to the participant completing study, withdrawing from the study, or due to the cutoff of data collection for the analysis. The censor date was the date of the end of study or the date of the data cutoff for participant who were ongoing. Participants who withdraw from the study after the baseline visit were censored at the last known date while on study. Based on Kaplan-Meier product limit estimates. "99999" = N/A
    End point type
    Secondary
    End point timeframe
    Overall: From first dose to end of study or data-cutoff date, whichever occurred first (up to approx 87 months); Specific Visits: At 2 weeks post first dose, then 3 months post first dose and every 3 months thereafter up until 81 months post first dose.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Number of subjects analysed
    725
    868
    881
    Units: Days
    median (confidence interval 95%)
        Overall Study
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
        Week 2 (15 Days)
    0.01 (0.01 to 0.03)
    0.01 (0.01 to 0.02)
    0.01 (0.00 to 0.01)
        Month 3 (92 Days)
    0.07 (0.05 to 0.09)
    0.05 (0.03 to 0.06)
    0.04 (0.03 to 0.05)
        Month 6 (183 Days)
    0.11 (0.09 to 0.13)
    0.09 (0.07 to 0.11)
    0.08 (0.06 to 0.10)
        Month 9 (274 Days)
    0.12 (0.10 to 0.15)
    0.12 (0.10 to 0.14)
    0.11 (0.09 to 0.13)
        Month 12 (365 Days)
    0.14 (0.12 to 0.17)
    0.15 (0.12 to 0.17)
    0.14 (0.11 to 0.16)
        Month 15 (456 Days)
    0.16 (0.13 to 0.19)
    0.17 (0.14 to 0.19)
    0.15 (0.13 to 0.17)
        Month 18 (547 Days)
    0.18 (0.15 to 0.21)
    0.18 (0.16 to 0.21)
    0.17 (0.15 to 0.20)
        Month 21 (638 Days)
    0.19 (0.16 to 0.22)
    0.20 (0.17 to 0.23)
    0.19 (0.16 to 0.21)
        Month 24 (729 Days)
    0.21 (0.18 to 0.24)
    0.22 (0.19 to 0.25)
    0.20 (0.18 to 0.23)
        Month 27 (820 Days)
    0.22 (0.19 to 0.25)
    0.23 (0.20 to 0.26)
    0.21 (0.19 to 0.24)
        Month 30 (911 Days)
    0.23 (0.20 to 0.27)
    0.23 (0.21 to 0.26)
    0.22 (0.20 to 0.25)
        Month 33 (1002 Days)
    0.24 (0.21 to 0.28)
    0.25 (0.22 to 0.28)
    0.23 (0.20 to 0.26)
        Month 36 (1093 Days)
    0.26 (0.23 to 0.29)
    0.26 (0.23 to 0.29)
    0.24 (0.21 to 0.27)
        Month 39 (1184 Days)
    0.27 (0.24 to 0.30)
    0.26 (0.24 to 0.30)
    0.25 (0.22 to 0.28)
        Month 42 (1275 Days)
    0.28 (0.25 to 0.32)
    0.27 (0.24 to 0.30)
    0.27 (0.24 to 0.30)
        Month 45 (1366 Days)
    0.29 (0.25 to 0.32)
    0.28 (0.25 to 0.31)
    0.28 (0.25 to 0.31)
        Month 48 (1457 Days)
    0.29 (0.26 to 0.32)
    0.29 (0.26 to 0.32)
    0.29 (0.26 to 0.32)
        Month 51 (1548 Days)
    0.30 (0.26 to 0.33)
    0.29 (0.26 to 0.32)
    0.29 (0.26 to 0.32)
        Month 54 (1639 Days)
    0.30 (0.27 to 0.34)
    0.30 (0.27 to 0.33)
    0.30 (0.27 to 0.34)
        Month 57 (1730 Days)
    0.30 (0.27 to 0.34)
    0.30 (0.27 to 0.34)
    0.31 (0.28 to 0.34)
        Month 60 (1821 Days)
    0.31 (0.28 to 0.35)
    0.31 (0.28 to 0.34)
    0.32 (0.29 to 0.35)
        Month 63 (1912 Days)
    0.32 (0.28 to 0.35)
    0.31 (0.28 to 0.35)
    0.33 (0.30 to 0.36)
        Month 66 (2003 Days)
    0.32 (0.29 to 0.36)
    0.32 (0.29 to 0.36)
    0.33 (0.30 to 0.36)
        Month 69 (2094 Days)
    0.33 (0.29 to 0.36)
    0.33 (0.30 to 0.36)
    0.33 (0.30 to 0.37)
        Month 72 (2185 Days)
    0.33 (0.29 to 0.36)
    0.33 (0.30 to 0.37)
    0.33 (0.30 to 0.37)
        Month 75 (2276 Days)
    0.33 (0.29 to 0.36)
    0.33 (0.30 to 0.37)
    0.34 (0.30 to 0.37)
        Month 78 (2367 Days)
    0.33 (0.29 to 0.36)
    0.33 (0.30 to 0.37)
    0.34 (0.30 to 0.37)
        Month 81 (2458 Days)
    0 (0 to 0)
    0.33 (0.30 to 0.37)
    0.34 (0.30 to 0.37)
    No statistical analyses for this end point

    Secondary: Time to Onset of Disability Progression as Defined by a Sustained Worsening in Expanded Disability Status Scale (EDSS)

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    End point title
    		 Time to Onset of Disability Progression as Defined by a Sustained Worsening in Expanded Disability Status Scale (EDSS)
    End point description
    Multiple sclerosis (MS) disability progression is defined as a sustained worsening in EDSS of 1.0 points or more from baseline, confirmed after a 3-month and 6-month period. The EDSS is a standardized method, widely accepted, numerical scale used to evaluate disability in people with multiple sclerosis (MS). The EDSS is evaluated according to signs and symptoms observed during a standard neurological examination. These clinical observations are classified in 7 FS scales, each of them grading signs and symptoms for different neurological functions: pyramidal, cerebellar, brainstem, sensory, bowel or bladder, visual, and cerebral. Derived using Kaplan-Meier estimates. "99999" = N/A
    End point type
    Secondary
    End point timeframe
    At 3 and 6 months post first dose.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Number of subjects analysed
    122
    160
    146
    Units: Days
    median (confidence interval 95%)
        Month 3
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
        Month 6
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Number of Participants Free of Gadolinium-Enhanced (GdE) Brain Lesions at Each Visit

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    End point title
    		 Number of Participants Free of Gadolinium-Enhanced (GdE) Brain Lesions at Each Visit
    End point description
    Number of participants without gadolinium enhanced (GdE) brain MRI lesions at each visit. Increased numbers of GdE lesions indicates an increase in the in the amount of active inflammation at the site and may be indicative of progressive disease. Based on cumulative number of GdE lesions at a participant level.
    End point type
    Secondary
    End point timeframe
    At baseline and every 12 months thereafter up until 72 months post first dose.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug ITT Population Parent Treatment Group: RPC1063 0.5 mg ITT Parent Treatment Group: RPC1063 1.0 mg ITT
    Number of subjects analysed
    740
    756
    760
    Units: Participants
        Baseline
    609
    662
    538
        Month 12
    644
    627
    622
        Month 24
    601
    596
    582
        Month 36
    576
    569
    538
        Month 48
    518
    517
    569
        Month 60
    528
    512
    478
        Month 72
    145
    149
    121
    No statistical analyses for this end point

    Secondary: Number of Participants Free of New or Enlarging T2 Lesions at Each Visit

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    End point title
    		 Number of Participants Free of New or Enlarging T2 Lesions at Each Visit
    End point description
    Number of participants without new or enlarging T2 brain MRI lesions at each visit. Some multiple Sclerosis (MS) lesions appear as bright spots in a T2-weighted MRI scan - these are called T2 lesions. The presence of new or larger T2 lesions may mean the participant is at higher risk of disability and may have a less favorable long-term outcome. Based on cumulative number of new or enlarging T2 lesions at a participant level.
    End point type
    Secondary
    End point timeframe
    At baseline and every 12 months thereafter up until 72 months post first dose.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Number of subjects analysed
    696
    722
    726
    Units: Participants
        Month 12
    322
    400
    419
        Month 24
    260
    323
    338
        Month 36
    220
    264
    271
        Month 48
    204
    223
    223
        Month 60
    177
    213
    209
        Month 72
    53
    59
    57
    No statistical analyses for this end point

    Secondary: Percent Change in Normalized Brain Volume (Atrophy) on Brain MRI Scans from Baseline at Each Visit

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    End point title
    		 Percent Change in Normalized Brain Volume (Atrophy) on Brain MRI Scans from Baseline at Each Visit
    End point description
    Percent change in normalized brain volume (Atrophy) on brain MRI scans from baseline at each visit. Brain atrophy can be seen in the earliest stages of multiple sclerosis (MS) and is a reliable predictor of future physical and cognitive disability.
    End point type
    Secondary
    End point timeframe
    At baseline and every 12 months thereafter up until approximately 87 months post first dose.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Number of subjects analysed
    596
    611
    623
    Units: Percent Volume Change from Baseline
    arithmetic mean (standard deviation)
        Month 12
    -0.407 ± 0.731
    -0.359 ± 0.607
    -0.385 ± 0.602
        Month 24
    -0.702 ± 0.809
    -0.657 ± 0.713
    -0.671 ± 0.706
        Month 36
    -0.992 ± 0.882
    -0.947 ± 0.825
    -0.977 ± 0.764
        Month 48
    -1.241 ± 1.012
    -1.214 ± 0.980
    -1.233 ± 0.949
        Month 60
    -1.485 ± 1.079
    -1.478 ± 1.014
    -1.544 ± 1.017
        Month 72
    -1.889 ± 1.288
    -1.696 ± 1.118
    -1.922 ± 1.290
        End of Treatment
    -1.283 ± 1.206
    -1.298 ± 1.133
    -1.355 ± 1.121
    No statistical analyses for this end point

    Secondary: Change in Multiple Sclerosis Functional Composite (MSFC) Score from Baseline at Each Applicable Visit

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    End point title
    		 Change in Multiple Sclerosis Functional Composite (MSFC) Score from Baseline at Each Applicable Visit
    End point description
    The MSFC is a three-part tool used in clinical studies to measure disability progression in patients with multiple sclerosis (MS). It includes the assessment of leg function, arm and hand function, and cognitive function. Scores from each of the three components are converted into Z-scores and averaged to create an overall composite score. "99999" = N/A
    End point type
    Secondary
    End point timeframe
    At baseline and every 12 months thereafter up until 84 months post first dose.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Number of subjects analysed
    702
    721
    732
    Units: MSFC Z-Score Change from Baseline
    arithmetic mean (standard deviation)
        MSFC Z Score Month 12
    0.058 ± 2.540
    -0.085 ± 0.488
    -0.064 ± 0.618
        MSFC Z Score Month 24
    -0.072 ± 0.855
    -0.082 ± 0.615
    -0.086 ± 0.632
        MSFC Z Score Month 36
    -0.105 ± 0.876
    -0.100 ± 0.529
    -0.109 ± 0.656
        MSFC Z Score Month 48
    -0.162 ± 1.025
    -0.148 ± 0.611
    -0.103 ± 1.460
        MSFC Z Score Month 60
    -0.182 ± 1.062
    -0.174 ± 0.675
    -0.148 ± 0.580
        MSFC Z Score Month 72
    -0.248 ± 1.256
    -0.239 ± 0.745
    -0.219 ± 0.672
        MSFC Z Score Month 84
    0 ± 0
    -0.099 ± 99999
    0 ± 0
        MSFC Z Score (LCLA) Month 12
    0.043 ± 1.919
    -0.059 ± 0.402
    -0.055 ± 0.483
        MSFC Z Score (LCLA) Month 24
    -0.056 ± 0.655
    -0.064 ± 0.483
    -0.074 ± 0.509
        MSFC Z Score (LCLA) Month 36
    -0.097 ± 0.686
    -0.089 ± 0.447
    -0.103 ± 0.542
        MSFC Z Score (LCLA) Month 48
    -0.158 ± 0.796
    -0.149 ± 0.525
    -0.103 ± 1.125
        MSFC Z Score (LCLA) Month 60
    -0.175 ± 0.837
    -0.181 ± 0.572
    -0.153 ± 0.505
        MSFC Z Score (LCLA) Month 72
    -0.237 ± 0.983
    -0.250 ± 0.624
    -0.213 ± 0.590
        MSFC Z Score (LCLA) Month 84
    0 ± 0
    -0.103 ± 99999
    0 ± 0
    No statistical analyses for this end point

    Secondary: Change in Multiple Sclerosis Quality of Life 54 Score from Baseline at Each Applicable Visit

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    End point title
    		 Change in Multiple Sclerosis Quality of Life 54 Score from Baseline at Each Applicable Visit
    End point description
    Multiple Sclerosis Quality of Life 54 (MSQOL-54) is a widely-used, health-related quality of life (HRQOL) instrument specific for multiple sclerosis (MS). This 54-item instrument generates 12 subscales along with two summary scores, and two additional single-item measures. The subscales are: physical function, role limitations-physical, role limitations-emotional, pain, emotional well-being, energy, health perceptions, social function, cognitive function, health distress, overall quality of life, and sexual function. "99999" = N/A
    End point type
    Secondary
    End point timeframe
    At baseline and every 12 months thereafter up until 84 months post first dose.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Number of subjects analysed
    659
    678
    678
    Units: MSQOL-54 Score Change from Baseline
    arithmetic mean (standard deviation)
        Month 12
    0.1 ± 10.68
    -0.1 ± 10.55
    0.2 ± 9.85
        Month 24
    0.8 ± 11.51
    -0.6 ± 10.76
    -0.3 ± 11.25
        Month 36
    0.1 ± 12.20
    -0.6 ± 11.23
    -0.4 ± 12.37
        Month 48
    -0.3 ± 12.60
    -1.4 ± 12.66
    -1.4 ± 12.71
        Month 60
    -1.1 ± 13.27
    -2.7 ± 13.11
    -2.1 ± 12.62
        Month 72
    -1.6 ± 14.97
    -3.0 ± 13.42
    -3.0 ± 13.88
        Month 84
    0 ± 0
    -0.3 ± 99999
    0 ± 0
    No statistical analyses for this end point

    Secondary: Change from Baseline in Volume of Gadolinium Enhanced T1 Lesions

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    End point title
    		 Change from Baseline in Volume of Gadolinium Enhanced T1 Lesions
    End point description
    Change from baseline in volume of gadolinium enhanced T1 lesions. T1-lesions are permanently damaged areas of the brain that appear as dark spots or “black holes” on a type of MRI scan. The growth of T1 lesions may mean the participant's Multiple Sclerosis (MS) is progressing.
    End point type
    Secondary
    End point timeframe
    At baseline and every 12 months thereafter up until 72 months post first dose.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Number of subjects analysed
    695
    723
    725
    Units: Volume (cm^3) Change from Baseline
    arithmetic mean (standard deviation)
        Month 12
    -0.092 ± 0.435
    -0.015 ± 0.229
    -0.004 ± 0.180
        Month 24
    -0.099 ± 0.431
    -0.017 ± 0.193
    0.009 ± 0.264
        Month 36
    -0.089 ± 0.485
    -0.018 ± 0.183
    0.012 ± 0.237
        Month 48
    -0.081 ± 0.467
    -0.012 ± 0.204
    0.017 ± 0.252
        Month 60
    -0.090 ± 0.448
    -0.017 ± 0.217
    0.000 ± 0.189
        Month 72
    -0.044 ± 0.145
    0.003 ± 0.157
    0.014 ± 0.307
    No statistical analyses for this end point

    Secondary: Change from Baseline in Volume of T2 Lesions

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    End point title
    		 Change from Baseline in Volume of T2 Lesions
    End point description
    Some multiple Sclerosis (MS) lesions appear as bright spots in a T2-weighted MRI scan - these are called T2 lesions. Larger T2 lesions may mean the participant is at higher risk of disability and may have a less favorable long-term outcome.
    End point type
    Secondary
    End point timeframe
    At baseline and every 12 months thereafter up until 72 months post first dose.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Number of subjects analysed
    696
    723
    726
    Units: Volume (cm^3) Change from Baseline
    arithmetic mean (standard deviation)
        Month 12
    0.190 ± 1.498
    0.174 ± 1.154
    0.278 ± 1.384
        Month 24
    0.307 ± 1.633
    0.303 ± 1.503
    0.518 ± 2.294
        Month 36
    0.536 ± 2.218
    0.456 ± 1.597
    0.711 ± 2.540
        Month 48
    0.695 ± 2.805
    0.583 ± 1.975
    0.952 ± 2.945
        Month 60
    0.709 ± 2.907
    0.683 ± 2.470
    0.987 ± 3.197
        Month 72
    0.889 ± 2.760
    0.557 ± 2.465
    1.234 ± 4.307
    No statistical analyses for this end point

    Secondary: Change from Baseline in Volume of Unenhancing T1 Lesions

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    End point title
    		 Change from Baseline in Volume of Unenhancing T1 Lesions
    End point description
    Change from baseline in volume of unenhancing T1 lesions. T1-lesions are permanently damaged areas of the brain that appear as dark spots or “black holes” on a type of MRI scan. The growth of T1 lesions may mean the participant's Multiple Sclerosis (MS) is progressing.
    End point type
    Secondary
    End point timeframe
    At baseline and every 12 months thereafter up until 72 months post first dose.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Number of subjects analysed
    695
    723
    726
    Units: Volume (cm^3) Change from Baseline
    arithmetic mean (standard deviation)
        Month 12
    -0.625 ± 2.012
    -0.772 ± 1.792
    -0.760 ± 1.869
        Month 24
    -0.192 ± 1.837
    -0.465 ± 1.735
    -0.455 ± 1.758
        Month 36
    -0.482 ± 2.913
    -0.618 ± 2.430
    -0.583 ± 2.249
        Month 48
    -0.398 ± 3.025
    -0.423 ± 2.439
    -0.403 ± 2.171
        Month 60
    -0.261 ± 2.885
    -0.356 ± 2.679
    -0.209 ± 2.134
        Month 72
    -0.047 ± 2.209
    -0.372 ± 3.257
    -0.256 ± 2.036
    No statistical analyses for this end point

    Secondary: Number of New Unenhancing T1 Lesions

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    End point title
    		 Number of New Unenhancing T1 Lesions
    End point description
    Number of new unenhancing T1 lesions. T1-lesions are permanently damaged areas of the brain that appear as dark spots or “black holes” on a type of MRI scan. The appearance of new T1 lesions may mean the participant's MS is progressing. Derived as the cumulative number of new or enlarging T1 lesions relative to baseline at a participant level.
    End point type
    Secondary
    End point timeframe
    At baseline and every 12 months thereafter up until 72 months post first dose.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Number of subjects analysed
    695
    722
    725
    Units: New or Enlarging Lesions.
    arithmetic mean (standard deviation)
        Month 12
    1.9 ± 4.66
    1.1 ± 2.86
    1.2 ± 3.16
        Month 24
    2.7 ± 6.30
    1.8 ± 5.04
    2.2 ± 5.24
        Month 36
    3.6 ± 8.41
    2.5 ± 7.04
    3.0 ± 7.55
        Month 48
    4.6 ± 11.02
    3.3 ± 8.67
    4.3 ± 10.56
        Month 60
    4.8 ± 11.43
    3.9 ± 10.18
    4.9 ± 12.39
        Month 72
    4.5 ± 10.11
    3.2 ± 8.76
    5.8 ± 16.55
    No statistical analyses for this end point

    Secondary: Average Number of New or Enlarging Hyperintense T2-Weighted Brain MRI Lesions Per Scan at Each Visit

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    End point title
    		 Average Number of New or Enlarging Hyperintense T2-Weighted Brain MRI Lesions Per Scan at Each Visit
    End point description
    Adjusted Mean of new enlarging T2 lesions per scan at each visit. Based on a negative binomial regression model, adjusted for parent study, region (Eastern Europe vs. Rest of the World), age at Baseline, and baseline number of GdE lesions. The natural log transformation of the number of available MRI scans per visit is used as an offset term. T2 Magnetic Resonance Imaging (MRI) sequences are used to highlight areas of demyelination in brain neurons, which happens when the outer layer of the neurons is damaged due to multiple sclerosis (MS) activity. T2 sequences can be used to count the total number of MS lesions, which look like bright white spots on T2 sequences, and can be called “hyperintense”.
    End point type
    Secondary
    End point timeframe
    At 12 months post first dose and every 12 months thereafter up until 72 months post first dose.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug ITT Population Parent Treatment Group: RPC1063 0.5 mg ITT Parent Treatment Group: RPC1063 1.0 mg ITT
    Number of subjects analysed
    696
    722
    726
    Units: New or Enlarging Lesions per Scan
    arithmetic mean (confidence interval 95%)
        Month 12
    1.532 (1.309 to 1.792)
    1.163 (0.995 to 1.360)
    1.302 (1.116 to 1.519)
        Month 24
    1.254 (1.072 to 1.466)
    1.005 (0.862 to 1.172)
    1.190 (1.022 to 1.385)
        Month 36
    1.136 (0.963 to 1.340)
    1.021 (0.872 to 1.197)
    1.142 (0.976 to 1.335)
        Month 48
    0.935 (0.786 to 1.112)
    0.915 (0.770 to 1.087)
    1.044 (0.883 to 1.234)
        Month 60
    0.791 (0.661 to 0.948)
    0.864 (0.728 to 1.025)
    0.935 (0.787 to 1.110)
        Month 72
    0.800 (0.566 to 1.132)
    0.780 (0.567 to 1.074)
    0.926 (0.684 to 1.255)
    No statistical analyses for this end point

    Secondary: Average Number of Gadolinium-Enhanced (GdE) Brain MRI Lesions Per Scan at Each Visit

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    End point title
    		 Average Number of Gadolinium-Enhanced (GdE) Brain MRI Lesions Per Scan at Each Visit
    End point description
    Number of gadolinium-enhanced (GdE) (also called GdE enhanced T1) brain MRI lesions per scan at each visit. Increased numbers of GdE lesions indicates an increase in the in the amount of active inflammation at the site and may be indicative of progressive disease. Based on a negative binomial regression model, adjusted for parent study, region (Eastern Europe vs. Rest of the World), age at Baseline, and Baseline number of GdE lesions.
    End point type
    Secondary
    End point timeframe
    At baseline and every 12 months thereafter up until 72 months post first dose.
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug ITT Population Parent Treatment Group: RPC1063 0.5 mg ITT Parent Treatment Group: RPC1063 1.0 mg ITT
    Number of subjects analysed
    740
    756
    760
    Units: New or Enlarging Lesions
    arithmetic mean (confidence interval 95%)
        Baseline
    0.460 (0.369 to 0.573)
    0.244 (0.193 to 0.308)
    0.177 (0.138 to 0.226)
        Month 12
    0.106 (0.076 to 0.147)
    0.130 (0.097 to 0.175)
    0.205 (0.155 to 0.273)
        Month 24
    0.138 (0.099 to 0.192)
    0.149 (0.109 to 0.205)
    0.224 (0.166 to 0.302)
        Month 36
    0.194 (0.134 to 0.281)
    0.155 (0.109 to 0.221)
    0.243 (0.173 to 0.342)
        Month 48
    0.230 (0.163 to 0.325)
    0.161 (0.108 to 0.241)
    0.245 (0.170 to 0.355)
        Month 60
    0.074 (0.043 to 0.125)
    0.062 (0.037 to 0.104)
    0.076 (0.046 to 0.126)
        Month 72
    0.099 (0.044 to 0.224)
    0.102 (0.049 to 0.213)
    0.082 (0.038 to 0.177)
    No statistical analyses for this end point

    Other pre-specified: Number of Participants Who Were Relapse Free

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    End point title
    		 Number of Participants Who Were Relapse Free
    End point description
    The number of participants who did not experience relapse. A relapse is defined as the occurrence of new or worsening neurological symptoms attributable to multiple sclerosis (MS) and immediately preceded by a relatively stable or improving neurological state of at least 30 days.
    End point type
    Other pre-specified
    End point timeframe
    From first dose to last dose of study treatment or data-cutoff date, whichever occurred first (up to approximately 87 months)
    End point values
    		 Parent Treatment Group IFN-B-1a 30 ug Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: RPC1063 1.0 mg
    Number of subjects analysed
    736
    877
    881
    Units: Participants
    513
    605
    605
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All events from first dose of OLE up to and including last dose +90 days
    Adverse event reporting additional description
    Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.1
    Reporting groups
    Reporting group title
    Parent Treatment Group: Placebo-RPC1063 0.5 mg
    Reporting group description
    		 Participants received a 7-day titration regimen of RPC1063 to reach the targeted dose of 1.0 mg which was taken by mouth once per day until the end of the trial or until the Sponsor discontinued the development program. Participants were instructed to take RPC1063 at approximately the same time each day with or without food.

    Reporting group title
    Parent Treatment Group: Placebo-RPC1063 1 mg
    Reporting group description
    		 Participants received a 7-day titration regimen of RPC1063 to reach the targeted dose of 1.0 mg which was taken by mouth once per day until the end of the trial or until the Sponsor discontinued the development program. Participants were instructed to take RPC1063 at approximately the same time each day with or without food.

    Reporting group title
    Parent Treatment Group: RPC1063 1 mg
    Reporting group description
    		 Participants received a 7-day titration regimen of RPC1063, as applicable to reach the targeted dose of 1.0 mg which was taken by mouth once per day until the end of the trial or until the Sponsor discontinued the development program. Participants were instructed to take RPC1063 at approximately the same time each day with or without food.

    Reporting group title
    Parent Treatment Group: RPC1063 0.5 mg
    Reporting group description
    		 Participants received a 7-day titration regimen of RPC1063, as applicable to reach the targeted dose of 1.0 mg which was taken by mouth once per day until the end of the trial or until the Sponsor discontinued the development program. Participants were instructed to take RPC1063 at approximately the same time each day with or without food.

    Reporting group title
    Parent Treatment Group: IFN beta-1a 30 ug
    Reporting group description
    		 Participants received a 7-day titration regimen of RPC1063, as applicable to reach the targeted dose of 1.0 mg which was taken by mouth once per day until the end of the trial or until the Sponsor discontinued the development program. Participants were instructed to take RPC1063 at approximately the same time each day with or without food.

    Serious adverse events
    		 Parent Treatment Group: Placebo-RPC1063 0.5 mg Parent Treatment Group: Placebo-RPC1063 1 mg Parent Treatment Group: RPC1063 1 mg Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: IFN beta-1a 30 ug
    Total subjects affected by serious adverse events
         subjects affected / exposed
    7 / 37 (18.92%)
    3 / 35 (8.57%)
    131 / 846 (15.48%)
    132 / 840 (15.71%)
    108 / 736 (14.67%)
         number of deaths (all causes)
    0
    0
    5
    5
    6
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Angiomyxoma
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Bladder papilloma
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colorectal adenoma
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clear cell renal cell carcinoma
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic myeloid leukaemia
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervix carcinoma
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    2 / 840 (0.24%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    1 / 840 (0.12%)
    2 / 736 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Borderline serous tumour of ovary
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Invasive lobular breast carcinoma
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leiomyoma
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    2 / 846 (0.24%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lipoma
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dermatofibrosarcoma protuberans
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endometrial adenocarcinoma
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal stromal tumour
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Glioblastoma
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Invasive breast carcinoma
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    3 / 846 (0.35%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic carcinoma metastatic
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian germ cell teratoma
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neurilemmoma benign
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant neoplasm progression
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasm malignant
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Myxoid liposarcoma
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Melanocytic naevus
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephroblastoma
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 35 (2.86%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine leiomyoma
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    5 / 840 (0.60%)
    6 / 736 (0.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 5
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thyroid cancer
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of the cervix
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seminoma
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    2 / 846 (0.24%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombophlebitis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Varicose vein
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    1 / 840 (0.12%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Circulatory collapse
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Medical device removal
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Haemorrhage in pregnancy
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abortion missed
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abortion spontaneous
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    2 / 736 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anembryonic gestation
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Sudden death
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Swelling face
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Social circumstances
    Miscarriage of partner
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Abnormal uterine bleeding
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Menometrorrhagia
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydrosalpinx
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Heavy menstrual bleeding
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endometrial hyperplasia
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervix disorder
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical dysplasia
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast dysplasia
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adnexa uteri cyst
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    2 / 736 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adenomyosis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    2 / 846 (0.24%)
    1 / 840 (0.12%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pelvic pain
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vaginal haemorrhage
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    2 / 840 (0.24%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine polyp
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine haemorrhage
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    2 / 846 (0.24%)
    1 / 840 (0.12%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive tract disorder
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectocele
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostatitis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Polycystic ovaries
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Perineal fistula
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Varicocele
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    2 / 846 (0.24%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    Pulmonary sarcoidosis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Cardiovascular somatic symptom disorder
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adjustment disorder with mixed anxiety and depressed mood
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute stress disorder
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    4 / 840 (0.48%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 7
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Needle issue
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Chronic hepatitis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Biliary polyp
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    1 / 840 (0.12%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 35 (2.86%)
    3 / 846 (0.35%)
    2 / 840 (0.24%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholestasis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Concussion
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    2 / 736 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Eye injury
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Forearm fracture
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foreign body in gastrointestinal tract
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fracture
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    2 / 846 (0.24%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple injuries
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fracture displacement
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hand fracture
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    2 / 840 (0.24%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intentional overdose
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    2 / 736 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint injury
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ligament injury
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ligament sprain
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary contusion
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    2 / 840 (0.24%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax traumatic
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nerve injury
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Traumatic haematoma
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Traumatic fracture
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    3 / 736 (0.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thermal burn
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    2 / 736 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Sebaceous naevus
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Kidney duplex
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydrocele
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cryptorchism
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrioventricular block second degree
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adams-Stokes syndrome
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    1 / 840 (0.12%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Sinoatrial block
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Cerebral haematoma
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebellar infarction
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Altered state of consciousness
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical radiculopathy
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    3 / 846 (0.35%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    2 / 846 (0.24%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoaesthesia
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    2 / 736 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    3 / 840 (0.36%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epilepsia partialis continua
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Encephalitis autoimmune
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radicular pain
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peroneal nerve palsy
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paraparesis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Optic neuritis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Noninfective encephalitis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neurological decompensation
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple sclerosis relapse
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Restless legs syndrome
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Monoparesis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Status epilepticus
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sensory disturbance
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    2 / 840 (0.24%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Trigeminal neuralgia
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Haemolytic anaemia
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune thrombocytopenia
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphadenitis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    2 / 846 (0.24%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Microcytic anaemia
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Deafness
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deafness neurosensory
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otosclerosis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Choroiditis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Iridocyclitis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blepharal pigmentation
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cataract
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Visual impairment
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uveitis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal polyp
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal perforation
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis ulcerative
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 35 (2.86%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal hernia
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoids thrombosed
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal inflammation
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    2 / 846 (0.24%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric disorder
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Functional gastrointestinal disorder
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inflammatory bowel disease
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    2 / 840 (0.24%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Irritable bowel syndrome
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ranula
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tooth loss
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermal cyst
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    2 / 846 (0.24%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eczema
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Decubitus ulcer
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psoriasis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urticaria
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Cystitis haemorrhagic
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Calculus urinary
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Kidney hypermobility
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neurogenic bladder
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urethral stenosis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urogenital fistula
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ureteric stenosis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Proteinuria
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Basedow's disease
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperadrenocorticism
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Goitre
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Bursal fluid accumulation
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    2 / 840 (0.24%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    4 / 840 (0.48%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Connective tissue disorder
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foot deformity
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemarthrosis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc disorder
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    2 / 846 (0.24%)
    0 / 840 (0.00%)
    3 / 736 (0.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chondromalacia
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    3 / 840 (0.36%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neck pain
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mandibular mass
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    2 / 736 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spondylolisthesis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    2 / 846 (0.24%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rheumatoid arthritis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    2 / 736 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal wall infection
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis infective
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    7 / 846 (0.83%)
    8 / 840 (0.95%)
    4 / 736 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 7
    0 / 8
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    Abscess limb
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute sinusitis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic hepatitis B
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic sinusitis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    2 / 846 (0.24%)
    4 / 840 (0.48%)
    3 / 736 (0.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 35 (0.00%)
    10 / 846 (1.18%)
    6 / 840 (0.71%)
    4 / 736 (0.54%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 10
    0 / 6
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis staphylococcal
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epididymitis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endometritis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    2 / 846 (0.24%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Echinococciasis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dacryocystitis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    2 / 840 (0.24%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonsillar abscess
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis media acute
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Orchitis
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lyme disease
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 35 (2.86%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung abscess
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Injection site abscess
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis A
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HIV infection
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Measles
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Salpingo-oophoritis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Salpingitis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis chronic
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    7 / 846 (0.83%)
    2 / 840 (0.24%)
    3 / 736 (0.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 7
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Progressive multifocal leukoencephalopathy
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    1 / 840 (0.12%)
    4 / 736 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vestibular neuronitis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    2 / 736 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Toxic shock syndrome
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    1 / 846 (0.12%)
    0 / 840 (0.00%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    0 / 840 (0.00%)
    1 / 736 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    0 / 846 (0.00%)
    1 / 840 (0.12%)
    0 / 736 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Parent Treatment Group: Placebo-RPC1063 0.5 mg Parent Treatment Group: Placebo-RPC1063 1 mg Parent Treatment Group: RPC1063 1 mg Parent Treatment Group: RPC1063 0.5 mg Parent Treatment Group: IFN beta-1a 30 ug
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    27 / 37 (72.97%)
    26 / 35 (74.29%)
    659 / 846 (77.90%)
    663 / 840 (78.93%)
    598 / 736 (81.25%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Skin papilloma
         subjects affected / exposed
    2 / 37 (5.41%)
    2 / 35 (5.71%)
    6 / 846 (0.71%)
    8 / 840 (0.95%)
    11 / 736 (1.49%)
         occurrences all number
    2
    2
    6
    8
    11
    Melanocytic naevus
         subjects affected / exposed
    2 / 37 (5.41%)
    1 / 35 (2.86%)
    12 / 846 (1.42%)
    8 / 840 (0.95%)
    6 / 736 (0.82%)
         occurrences all number
    2
    1
    13
    8
    6
    Vascular disorders
    Hypertension
         subjects affected / exposed
    5 / 37 (13.51%)
    2 / 35 (5.71%)
    60 / 846 (7.09%)
    81 / 840 (9.64%)
    76 / 736 (10.33%)
         occurrences all number
    5
    2
    67
    93
    82
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    2 / 37 (5.41%)
    3 / 35 (8.57%)
    29 / 846 (3.43%)
    27 / 840 (3.21%)
    17 / 736 (2.31%)
         occurrences all number
    2
    3
    30
    30
    17
    Immune system disorders
    Immunisation reaction
         subjects affected / exposed
    0 / 37 (0.00%)
    2 / 35 (5.71%)
    6 / 846 (0.71%)
    9 / 840 (1.07%)
    5 / 736 (0.68%)
         occurrences all number
    0
    2
    10
    12
    5
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 37 (5.41%)
    0 / 35 (0.00%)
    30 / 846 (3.55%)
    32 / 840 (3.81%)
    18 / 736 (2.45%)
         occurrences all number
    2
    0
    34
    34
    21
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 37 (0.00%)
    4 / 35 (11.43%)
    29 / 846 (3.43%)
    26 / 840 (3.10%)
    28 / 736 (3.80%)
         occurrences all number
    0
    4
    34
    28
    30
    Depression
         subjects affected / exposed
    0 / 37 (0.00%)
    2 / 35 (5.71%)
    41 / 846 (4.85%)
    45 / 840 (5.36%)
    38 / 736 (5.16%)
         occurrences all number
    0
    2
    45
    54
    43
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    3 / 37 (8.11%)
    3 / 35 (8.57%)
    34 / 846 (4.02%)
    40 / 840 (4.76%)
    46 / 736 (6.25%)
         occurrences all number
    3
    3
    44
    54
    67
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 37 (5.41%)
    1 / 35 (2.86%)
    15 / 846 (1.77%)
    20 / 840 (2.38%)
    23 / 736 (3.13%)
         occurrences all number
    2
    1
    15
    24
    32
    Blood cholesterol increased
         subjects affected / exposed
    0 / 37 (0.00%)
    4 / 35 (11.43%)
    8 / 846 (0.95%)
    7 / 840 (0.83%)
    5 / 736 (0.68%)
         occurrences all number
    0
    4
    8
    7
    5
    Blood triglycerides increased
         subjects affected / exposed
    0 / 37 (0.00%)
    2 / 35 (5.71%)
    3 / 846 (0.35%)
    3 / 840 (0.36%)
    4 / 736 (0.54%)
         occurrences all number
    0
    2
    3
    3
    4
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 37 (2.70%)
    4 / 35 (11.43%)
    61 / 846 (7.21%)
    63 / 840 (7.50%)
    71 / 736 (9.65%)
         occurrences all number
    1
    4
    85
    82
    94
    Low density lipoprotein increased
         subjects affected / exposed
    0 / 37 (0.00%)
    2 / 35 (5.71%)
    4 / 846 (0.47%)
    3 / 840 (0.36%)
    1 / 736 (0.14%)
         occurrences all number
    0
    3
    4
    3
    1
    Lymphocyte count decreased
         subjects affected / exposed
    7 / 37 (18.92%)
    2 / 35 (5.71%)
    81 / 846 (9.57%)
    77 / 840 (9.17%)
    68 / 736 (9.24%)
         occurrences all number
    8
    2
    104
    106
    86
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 37 (0.00%)
    2 / 35 (5.71%)
    13 / 846 (1.54%)
    8 / 840 (0.95%)
    11 / 736 (1.49%)
         occurrences all number
    0
    3
    20
    9
    13
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    0 / 37 (0.00%)
    2 / 35 (5.71%)
    3 / 846 (0.35%)
    3 / 840 (0.36%)
    6 / 736 (0.82%)
         occurrences all number
    0
    2
    3
    3
    6
    Nervous system disorders
    Paraesthesia
         subjects affected / exposed
    1 / 37 (2.70%)
    2 / 35 (5.71%)
    20 / 846 (2.36%)
    10 / 840 (1.19%)
    12 / 736 (1.63%)
         occurrences all number
    1
    2
    21
    11
    12
    Muscle spasticity
         subjects affected / exposed
    0 / 37 (0.00%)
    2 / 35 (5.71%)
    13 / 846 (1.54%)
    9 / 840 (1.07%)
    3 / 736 (0.41%)
         occurrences all number
    0
    2
    14
    9
    3
    Headache
         subjects affected / exposed
    2 / 37 (5.41%)
    7 / 35 (20.00%)
    144 / 846 (17.02%)
    142 / 840 (16.90%)
    131 / 736 (17.80%)
         occurrences all number
    2
    25
    298
    303
    242
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    4 / 37 (10.81%)
    4 / 35 (11.43%)
    36 / 846 (4.26%)
    31 / 840 (3.69%)
    28 / 736 (3.80%)
         occurrences all number
    7
    4
    37
    46
    35
    Lymphopenia
         subjects affected / exposed
    3 / 37 (8.11%)
    6 / 35 (17.14%)
    73 / 846 (8.63%)
    92 / 840 (10.95%)
    83 / 736 (11.28%)
         occurrences all number
    6
    8
    99
    125
    108
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 37 (0.00%)
    2 / 35 (5.71%)
    12 / 846 (1.42%)
    15 / 840 (1.79%)
    13 / 736 (1.77%)
         occurrences all number
    0
    2
    13
    15
    18
    Gastritis
         subjects affected / exposed
    1 / 37 (2.70%)
    2 / 35 (5.71%)
    11 / 846 (1.30%)
    17 / 840 (2.02%)
    15 / 736 (2.04%)
         occurrences all number
    1
    2
    12
    17
    17
    Diarrhoea
         subjects affected / exposed
    1 / 37 (2.70%)
    4 / 35 (11.43%)
    25 / 846 (2.96%)
    37 / 840 (4.40%)
    21 / 736 (2.85%)
         occurrences all number
    1
    5
    31
    42
    26
    Haemorrhoids
         subjects affected / exposed
    2 / 37 (5.41%)
    0 / 35 (0.00%)
    7 / 846 (0.83%)
    9 / 840 (1.07%)
    8 / 736 (1.09%)
         occurrences all number
    2
    0
    7
    10
    8
    Vomiting
         subjects affected / exposed
    1 / 37 (2.70%)
    3 / 35 (8.57%)
    7 / 846 (0.83%)
    8 / 840 (0.95%)
    5 / 736 (0.68%)
         occurrences all number
    1
    3
    16
    9
    8
    Skin and subcutaneous tissue disorders
    Eczema
         subjects affected / exposed
    1 / 37 (2.70%)
    2 / 35 (5.71%)
    4 / 846 (0.47%)
    6 / 840 (0.71%)
    1 / 736 (0.14%)
         occurrences all number
    1
    2
    4
    7
    1
    Dermatitis allergic
         subjects affected / exposed
    2 / 37 (5.41%)
    0 / 35 (0.00%)
    5 / 846 (0.59%)
    7 / 840 (0.83%)
    5 / 736 (0.68%)
         occurrences all number
    2
    0
    5
    7
    5
    Renal and urinary disorders
    Urinary incontinence
         subjects affected / exposed
    2 / 37 (5.41%)
    1 / 35 (2.86%)
    5 / 846 (0.59%)
    7 / 840 (0.83%)
    6 / 736 (0.82%)
         occurrences all number
    2
    1
    5
    11
    7
    Nephrolithiasis
         subjects affected / exposed
    2 / 37 (5.41%)
    0 / 35 (0.00%)
    3 / 846 (0.35%)
    6 / 840 (0.71%)
    2 / 736 (0.27%)
         occurrences all number
    2
    0
    3
    6
    2
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    2 / 37 (5.41%)
    3 / 35 (8.57%)
    32 / 846 (3.78%)
    29 / 840 (3.45%)
    26 / 736 (3.53%)
         occurrences all number
    3
    4
    41
    31
    33
    Back pain
         subjects affected / exposed
    7 / 37 (18.92%)
    6 / 35 (17.14%)
    71 / 846 (8.39%)
    81 / 840 (9.64%)
    72 / 736 (9.78%)
         occurrences all number
    7
    8
    103
    99
    89
    Arthralgia
         subjects affected / exposed
    1 / 37 (2.70%)
    3 / 35 (8.57%)
    61 / 846 (7.21%)
    53 / 840 (6.31%)
    43 / 736 (5.84%)
         occurrences all number
    2
    4
    67
    61
    48
    Infections and infestations
    Herpes zoster
         subjects affected / exposed
    2 / 37 (5.41%)
    2 / 35 (5.71%)
    12 / 846 (1.42%)
    17 / 840 (2.02%)
    13 / 736 (1.77%)
         occurrences all number
    2
    2
    12
    19
    13
    COVID-19
         subjects affected / exposed
    8 / 37 (21.62%)
    7 / 35 (20.00%)
    136 / 846 (16.08%)
    130 / 840 (15.48%)
    116 / 736 (15.76%)
         occurrences all number
    8
    7
    148
    136
    124
    Bronchitis
         subjects affected / exposed
    1 / 37 (2.70%)
    3 / 35 (8.57%)
    55 / 846 (6.50%)
    58 / 840 (6.90%)
    38 / 736 (5.16%)
         occurrences all number
    1
    3
    68
    75
    46
    Viral infection
         subjects affected / exposed
    1 / 37 (2.70%)
    2 / 35 (5.71%)
    3 / 846 (0.35%)
    7 / 840 (0.83%)
    7 / 736 (0.95%)
         occurrences all number
    1
    2
    3
    9
    8
    Urinary tract infection
         subjects affected / exposed
    8 / 37 (21.62%)
    3 / 35 (8.57%)
    58 / 846 (6.86%)
    52 / 840 (6.19%)
    48 / 736 (6.52%)
         occurrences all number
    11
    6
    97
    106
    75
    Upper respiratory tract infection
         subjects affected / exposed
    5 / 37 (13.51%)
    8 / 35 (22.86%)
    97 / 846 (11.47%)
    101 / 840 (12.02%)
    99 / 736 (13.45%)
         occurrences all number
    7
    11
    143
    162
    146
    Sinusitis
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 35 (0.00%)
    30 / 846 (3.55%)
    33 / 840 (3.93%)
    37 / 736 (5.03%)
         occurrences all number
    1
    0
    38
    38
    51
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 35 (0.00%)
    46 / 846 (5.44%)
    52 / 840 (6.19%)
    46 / 736 (6.25%)
         occurrences all number
    0
    0
    69
    91
    68
    Respiratory tract infection
         subjects affected / exposed
    2 / 37 (5.41%)
    1 / 35 (2.86%)
    53 / 846 (6.26%)
    56 / 840 (6.67%)
    53 / 736 (7.20%)
         occurrences all number
    2
    1
    82
    86
    88
    Pharyngitis
         subjects affected / exposed
    0 / 37 (0.00%)
    3 / 35 (8.57%)
    35 / 846 (4.14%)
    39 / 840 (4.64%)
    30 / 736 (4.08%)
         occurrences all number
    0
    3
    47
    49
    37
    Nasopharyngitis
         subjects affected / exposed
    5 / 37 (13.51%)
    9 / 35 (25.71%)
    177 / 846 (20.92%)
    176 / 840 (20.95%)
    164 / 736 (22.28%)
         occurrences all number
    7
    20
    295
    316
    320
    Influenza
         subjects affected / exposed
    0 / 37 (0.00%)
    4 / 35 (11.43%)
    24 / 846 (2.84%)
    32 / 840 (3.81%)
    24 / 736 (3.26%)
         occurrences all number
    0
    7
    33
    40
    28
    Metabolism and nutrition disorders
    Dyslipidaemia
         subjects affected / exposed
    0 / 37 (0.00%)
    2 / 35 (5.71%)
    11 / 846 (1.30%)
    10 / 840 (1.19%)
    15 / 736 (2.04%)
         occurrences all number
    0
    2
    11
    10
    15
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 37 (2.70%)
    3 / 35 (8.57%)
    33 / 846 (3.90%)
    36 / 840 (4.29%)
    32 / 736 (4.35%)
         occurrences all number
    1
    4
    36
    37
    34

    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
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    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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