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    Clinical Trial Results:
    An open-label, multicenter, multinational extension study of the long-term safety and pharmacokinetics of repeated biweekly infusions of avalglucosidase alfa (neoGAA, GZ402666) in patients with Pompe disease

    Summary
    EudraCT number
    		 2013-003321-28
    Trial protocol
    		 BE   NL   DK   DE   FR  
    Global end of trial date
    12 Dec 2022

    Results information
    Results version number
    		 v2(current)
    This version publication date
    19 Apr 2024
    First version publication date
    24 Dec 2023
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    EudraCT results are updated to maintain the consistency between EudraCT results and Clinicaltrials.gov results.

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    LTS13769
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02032524
    WHO universal trial number (UTN)
    		 U1111-1147-3439
    Sponsors
    Sponsor organisation name
    Genzyme Corporation
    Sponsor organisation address
    450 Water Street, Cambridge, Massachusetts, United States, 02141
    Public contact
    Trial Transparency Team, Sanofi-Aventis Recherche & Developpement, contact-us@sanofi.com
    Scientific contact
    Trial Transparency Team, Sanofi-Aventis Recherche & Developpement, contact-us@sanofi.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    16 Feb 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    12 Dec 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the long-term safety and pharmacokinetics (PK) of avalglucosidase alfa in participants with Pompe disease who have previously completed an avalglucosidase alfa study.
    Protection of trial subjects
    Subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject is participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    27 Feb 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Belgium: 2
    Country: Number of subjects enrolled
    Denmark: 1
    Country: Number of subjects enrolled
    France: 4
    Country: Number of subjects enrolled
    Germany: 3
    Country: Number of subjects enrolled
    Netherlands: 2
    Country: Number of subjects enrolled
    United Kingdom: 1
    Country: Number of subjects enrolled
    United States: 11
    Worldwide total number of subjects
    24
    EEA total number of subjects
    12
    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)
    20
    From 65 to 84 years
    4
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The study was conducted at 17 centers in 7 countries. A total of 21 participants completed the open-label study TDR12857 (NCT01898364). Of which, 19 participants were enrolled in this study. There was no screening period in this study.

    Pre-assignment
    Screening details
    		 Participants who completed the open-label TDR12857 study were part of this study. This was an open-label study. As prespecified, data were analyzed and presented combinedly for studies TDR12857 and LTS13769.

    Period 1
    Period 1 title
    TDR12857 Study
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Group 1: Avalglucosidase alfa 5 mg/kg
    Arm description
    		 Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 milligram per kilogram (mg/kg) intravenous (IV) infusion every other week (qow) for up to 454 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Avalglucosidase alfa
    Investigational medicinal product code
    neoGAA, GZ402666
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Avalglucosidase alfa 5 mg/kg was administered through IV infusion qow for up to 454 weeks.

    Arm title
    		 Group 1: Avalglucosidase alfa 10 mg/kg
    Arm description
    		 Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Avalglucosidase alfa
    Investigational medicinal product code
    neoGAA, GZ402666
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Avalglucosidase alfa 10 mg/kg was administered through IV infusion qow for up to 432 weeks.

    Arm title
    		 Group 1: Avalglucosidase alfa 20 mg/kg
    Arm description
    		 Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 421 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Avalglucosidase alfa
    Investigational medicinal product code
    neoGAA, GZ402666
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Avalglucosidase alfa 20 mg/kg was administered through IV infusion qow for up to 421 weeks.

    Arm title
    		 Group 2: Avalglucosidase alfa 5 mg/kg
    Arm description
    		 Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 424 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Avalglucosidase alfa
    Investigational medicinal product code
    neoGAA, GZ402666
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Avalglucosidase alfa 5 mg/kg was administered through IV infusion qow for up to 424 weeks.

    Arm title
    		 Group 2: Avalglucosidase alfa 10 mg/kg
    Arm description
    		 Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 450 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Avalglucosidase alfa
    Investigational medicinal product code
    neoGAA, GZ402666
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Avalglucosidase alfa 10 mg/kg was administered through IV infusion qow for up to 450 weeks.

    Arm title
    		 Group 2: Avalglucosidase alfa 20 mg/kg
    Arm description
    		 Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 445 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Avalglucosidase alfa
    Investigational medicinal product code
    neoGAA, GZ402666
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Avalglucosidase alfa 20 mg/kg was administered through IV infusion qow for up to 445 weeks.

    Number of subjects in period 1
    		Group 1: Avalglucosidase alfa 5 mg/kg Group 1: Avalglucosidase alfa 10 mg/kg Group 1: Avalglucosidase alfa 20 mg/kg Group 2: Avalglucosidase alfa 5 mg/kg Group 2: Avalglucosidase alfa 10 mg/kg Group 2: Avalglucosidase alfa 20 mg/kg
    Started
    4
    3
    3
    4
    4
    6
    Completed
    3
    3
    3
    3
    4
    5
    Not completed
    1
    0
    0
    1
    0
    1
         Wishes To Withdraw
    -
    -
    -
    1
    -
    1
         Adverse Event
    1
    -
    -
    -
    -
    -
    Period 2
    Period 2 title
    LTS13769 Study
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Group 1: Avalglucosidase alfa 5 mg/kg
    Arm description
    		 Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 454 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Avalglucosidase alfa
    Investigational medicinal product code
    neoGAA, GZ402666
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Avalglucosidase alfa 5 mg/kg was administered through IV infusion qow for up to 454 weeks.

    Arm title
    		 Group 1: Avalglucosidase alfa 10 mg/kg
    Arm description
    		 Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Avalglucosidase alfa
    Investigational medicinal product code
    neoGAA, GZ402666
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Avalglucosidase alfa 10 mg/kg was administered through IV infusion qow for up to 432 weeks.

    Arm title
    		 Group 1: Avalglucosidase alfa 20 mg/kg
    Arm description
    		 Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 421 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Avalglucosidase alfa
    Investigational medicinal product code
    neoGAA, GZ402666
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Avalglucosidase alfa 20 mg/kg was administered through IV infusion qow for up to 421 weeks.

    Arm title
    		 Group 2: Avalglucosidase alfa 5 mg/kg
    Arm description
    		 Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 424 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Avalglucosidase alfa
    Investigational medicinal product code
    neoGAA, GZ402666
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Avalglucosidase alfa 5 mg/kg was administered through IV infusion qow for up to 424 weeks.

    Arm title
    		 Group 2: Avalglucosidase alfa 10 mg/kg
    Arm description
    		 Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 450 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Avalglucosidase alfa
    Investigational medicinal product code
    neoGAA, GZ402666
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Avalglucosidase alfa 10 mg/kg was administered through IV infusion qow for up to 450 weeks.

    Arm title
    		 Group 2: Avalglucosidase alfa 20 mg/kg
    Arm description
    		 Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 445 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Avalglucosidase alfa
    Investigational medicinal product code
    neoGAA, GZ402666
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Avalglucosidase alfa 20 mg/kg was administered through IV infusion qow for up to 445 weeks.

    Number of subjects in period 2 [1]
    		Group 1: Avalglucosidase alfa 5 mg/kg Group 1: Avalglucosidase alfa 10 mg/kg Group 1: Avalglucosidase alfa 20 mg/kg Group 2: Avalglucosidase alfa 5 mg/kg Group 2: Avalglucosidase alfa 10 mg/kg Group 2: Avalglucosidase alfa 20 mg/kg
    Started
    3
    2
    3
    3
    3
    5
    Completed
    3
    1
    2
    3
    2
    4
    Not completed
    0
    1
    1
    0
    1
    1
         Wishes To Withdraw
    -
    1
    -
    -
    1
    -
         Adverse Event
    -
    -
    1
    -
    -
    -
         Unspecified
    -
    -
    -
    -
    -
    1
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Only eligible participants enrolled in LTS13769 study.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Group 1: Avalglucosidase alfa 5 mg/kg
    Reporting group description
    		 Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 milligram per kilogram (mg/kg) intravenous (IV) infusion every other week (qow) for up to 454 weeks.

    Reporting group title
    Group 1: Avalglucosidase alfa 10 mg/kg
    Reporting group description
    		 Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.

    Reporting group title
    Group 1: Avalglucosidase alfa 20 mg/kg
    Reporting group description
    		 Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 421 weeks.

    Reporting group title
    Group 2: Avalglucosidase alfa 5 mg/kg
    Reporting group description
    		 Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 424 weeks.

    Reporting group title
    Group 2: Avalglucosidase alfa 10 mg/kg
    Reporting group description
    		 Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 450 weeks.

    Reporting group title
    Group 2: Avalglucosidase alfa 20 mg/kg
    Reporting group description
    		 Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 445 weeks.

    Reporting group values
    		 Group 1: Avalglucosidase alfa 5 mg/kg Group 1: Avalglucosidase alfa 10 mg/kg Group 1: Avalglucosidase alfa 20 mg/kg Group 2: Avalglucosidase alfa 5 mg/kg Group 2: Avalglucosidase alfa 10 mg/kg Group 2: Avalglucosidase alfa 20 mg/kg Total
    Number of subjects
    		 4 3 3 4 4 6 24
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0 0
        Adults (18-64 years)
    		 3 3 2 3 4 5 20
        From 65-84 years
    		 1 0 1 1 0 1 4
        85 years and over
    		 0 0 0 0 0 0 0
    Gender categorical
    Units: Subjects
        Female
    		 3 3 1 2 1 2 12
        Male
    		 1 0 2 2 3 4 12
    Race
    Units: Subjects
        White
    		 4 1 3 4 3 6 21
        Black or African American
    		 0 0 0 0 1 0 1
        Not Reported
    		 0 1 0 0 0 0 1
        Multiple
    		 0 1 0 0 0 0 1

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Group 1: Avalglucosidase alfa 5 mg/kg
    Reporting group description
    		 Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 milligram per kilogram (mg/kg) intravenous (IV) infusion every other week (qow) for up to 454 weeks.

    Reporting group title
    Group 1: Avalglucosidase alfa 10 mg/kg
    Reporting group description
    		 Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.

    Reporting group title
    Group 1: Avalglucosidase alfa 20 mg/kg
    Reporting group description
    		 Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 421 weeks.

    Reporting group title
    Group 2: Avalglucosidase alfa 5 mg/kg
    Reporting group description
    		 Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 424 weeks.

    Reporting group title
    Group 2: Avalglucosidase alfa 10 mg/kg
    Reporting group description
    		 Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 450 weeks.

    Reporting group title
    Group 2: Avalglucosidase alfa 20 mg/kg
    Reporting group description
    		 Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 445 weeks.
    Reporting group title
    Group 1: Avalglucosidase alfa 5 mg/kg
    Reporting group description
    		 Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 454 weeks.

    Reporting group title
    Group 1: Avalglucosidase alfa 10 mg/kg
    Reporting group description
    		 Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.

    Reporting group title
    Group 1: Avalglucosidase alfa 20 mg/kg
    Reporting group description
    		 Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 421 weeks.

    Reporting group title
    Group 2: Avalglucosidase alfa 5 mg/kg
    Reporting group description
    		 Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 424 weeks.

    Reporting group title
    Group 2: Avalglucosidase alfa 10 mg/kg
    Reporting group description
    		 Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 450 weeks.

    Reporting group title
    Group 2: Avalglucosidase alfa 20 mg/kg
    Reporting group description
    		 Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 445 weeks.

    Subject analysis set title
    Group 1: Avalglucosidase Alfa
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 or 10 or 20 mg/kg IV infusion qow for up to 454 weeks.

    Subject analysis set title
    Group 2: Avalglucosidase Alfa
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 5 or 10 or 20 mg/kg IV infusion qow for up to 450 weeks.

    Primary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Infusion Associated Reactions (IARs) and Deaths

    		 Close Top of page
    End point title
    		 Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Infusion Associated Reactions (IARs) and Deaths [1]
    End point description
    An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An serious AE (SAE) is any untoward medical occurrence that results: death or life-threatening or inpatient hospitalization or prolongation of existing hospitalization or persistent or significant disability or congenital anomaly or medically important event. TEAEs are defined as AEs that develop or worsen during the on-treatment period [that is, from the time of first dose of IMP up to 4 weeks after the last administration of the IMP]. Protocol-defined IARs were defined as AEs that occur during either the infusion or post-infusion observation period (that is, up to 2 hours or longer following the infusion as per the Investigator’s discretion) which were deemed to be related or possibly related to the IMP. Results are based on the safety analysis set.
    End point type
    Primary
    End point timeframe
    From first dose of investigational medicinal product (IMP) up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint is descriptive in nature, no statistical analysis is provided.
    End point values
    		 Group 1: Avalglucosidase alfa 5 mg/kg Group 1: Avalglucosidase alfa 10 mg/kg Group 1: Avalglucosidase alfa 20 mg/kg Group 2: Avalglucosidase alfa 5 mg/kg Group 2: Avalglucosidase alfa 10 mg/kg Group 2: Avalglucosidase alfa 20 mg/kg
    Number of subjects analysed
    4
    3
    3
    4
    4
    6
    Units: participants
        Any TEAEs
    4
    3
    3
    4
    4
    6
        TESAEs
    3
    1
    1
    1
    1
    2
        Protocol-defined IARs
    2
    0
    2
    2
    0
    1
        Any TEAE leading to death
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Number of Participants With Clinically Significant Physical Examination Abnormalities

    		 Close Top of page
    End point title
    		 Number of Participants With Clinically Significant Physical Examination Abnormalities [2]
    End point description
    Physical examination included, at a minimum, an assessment of the participant’s general appearance; skin; head, eyes, ears, nose, and throat; examinations of lymph nodes, abdomen, extremities/joints, neurological and mental status; heart and respiratory auscultation; peripheral arterial pulse; and pupil, knee, achilles, and plantar reflexes. Results are based on the safety analysis set which included all participants who received at least 1 complete infusion of IMP.
    End point type
    Primary
    End point timeframe
    From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint is descriptive in nature, no statistical analysis is provided.
    End point values
    		 Group 1: Avalglucosidase alfa 5 mg/kg Group 1: Avalglucosidase alfa 10 mg/kg Group 1: Avalglucosidase alfa 20 mg/kg Group 2: Avalglucosidase alfa 5 mg/kg Group 2: Avalglucosidase alfa 10 mg/kg Group 2: Avalglucosidase alfa 20 mg/kg
    Number of subjects analysed
    4
    3
    3
    4
    4
    6
    Units: participants
        Achilles Reflexes
    0
    0
    0
    0
    0
    1
        General Appearance
    0
    0
    0
    0
    0
    1
        Knee Reflexes
    0
    0
    0
    0
    0
    1
        Lymph Nodes
    0
    0
    0
    0
    0
    1
        Neurological Status
    0
    0
    0
    0
    2
    1
    No statistical analyses for this end point

    Primary: Number of Participants With Potentially Clinically Significant Abnormalities in Biochemistry

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    End point title
    		 Number of Participants With Potentially Clinically Significant Abnormalities in Biochemistry [3]
    End point description
    Blood samples were collected to determine the clinical chemistry laboratory abnormalities. Results are based on the safety analysis set which included all participants who received at least 1 complete infusion of IMP. Here, mmol/L= millimoles per liter, LLN= lower limit of normal, and ULN= upper limit of normal.
    End point type
    Primary
    End point timeframe
    From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint is descriptive in nature, no statistical analysis is provided.
    End point values
    		 Group 1: Avalglucosidase alfa 5 mg/kg Group 1: Avalglucosidase alfa 10 mg/kg Group 1: Avalglucosidase alfa 20 mg/kg Group 2: Avalglucosidase alfa 5 mg/kg Group 2: Avalglucosidase alfa 10 mg/kg Group 2: Avalglucosidase alfa 20 mg/kg
    Number of subjects analysed
    4
    3
    3
    4
    4
    6
    Units: participants
        Glucose: <=3.9 mmol/L and < LLN
    2
    2
    2
    1
    2
    1
        Glucose:>=11.1 mmol/L(unfasted);>=7 mmol/L(fasted)
    2
    0
    1
    1
    1
    3
        Sodium: <=129 mmol/L
    0
    0
    0
    1
    0
    1
        Sodium: >=160 mmol/L
    0
    0
    0
    0
    0
    0
        Potassium: <3 mmol/L
    0
    0
    0
    1
    1
    0
        Potassium: >=5.5 mmol/L
    0
    0
    0
    0
    0
    1
        Chloride: <80 mmol/L
    0
    0
    0
    0
    0
    0
        Chloride: >115 mmol/L
    0
    0
    0
    0
    0
    0
        Albumin: <=25 gram per liter (g/L)
    0
    0
    0
    0
    0
    0
        Creatinine: >=150 micromoles/L (Adults)
    0
    0
    0
    0
    0
    1
        Creatinine: >=100% change from baseline
    0
    0
    0
    0
    0
    2
        Creatinine: >=30% change from baseline
    0
    0
    0
    1
    0
    2
        Urea Nitrogen: >=17 mmol/L
    0
    0
    1
    0
    0
    0
        Aspartate Aminotransferase: >3 ULN
    0
    2
    0
    1
    0
    0
        Aspartate Aminotransferase: >5 ULN
    0
    1
    0
    0
    0
    0
        Aspartate Aminotransferase: >10 ULN
    0
    0
    0
    0
    0
    0
        Alanine Aminotransferase: >3 ULN
    0
    2
    0
    1
    0
    0
        Alanine Aminotransferase: >5 ULN
    0
    1
    0
    0
    0
    0
        Alanine Aminotransferase: >10 ULN
    0
    0
    0
    0
    0
    0
        Alanine Aminotransferase >3ULN and Bilirubin >2ULN
    0
    0
    0
    0
    0
    0
        Alkaline Phosphatase: >1.5 ULN
    0
    0
    0
    0
    0
    0
        Total Bilirubin: >1.5 ULN
    1
    0
    1
    0
    0
    2
        Total Bilirubin: >2 ULN
    0
    0
    0
    0
    0
    0
        Direct Bilirubin >35% Bilirubin; Bilirubin >1.5ULN
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Number of Participants With Potentially Clinically Significant Abnormalities in Hematology

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    End point title
    		 Number of Participants With Potentially Clinically Significant Abnormalities in Hematology [4]
    End point description
    Blood samples were collected to determine the hematology laboratory significant abnormalities. Results are based on the safety analysis set which included all participants who received at least 1 complete infusion of IMP. Here, v/v= volume per volume and Bk= black.
    End point type
    Primary
    End point timeframe
    From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint is descriptive in nature, no statistical analysis is provided.
    End point values
    		 Group 1: Avalglucosidase alfa 5 mg/kg Group 1: Avalglucosidase alfa 10 mg/kg Group 1: Avalglucosidase alfa 20 mg/kg Group 2: Avalglucosidase alfa 5 mg/kg Group 2: Avalglucosidase alfa 10 mg/kg Group 2: Avalglucosidase alfa 20 mg/kg
    Number of subjects analysed
    4
    3
    3
    4
    4
    6
    Units: participants
        Hemoglobin: <=115 g/L (Male); <=95 g/L (Female)
    1
    0
    1
    0
    0
    1
        Hemoglobin: >=185 g/L (Male); >=165 g/L (Female)
    0
    0
    0
    0
    1
    0
        Hemoglobin: Decrease from baseline >=20 g/L
    1
    1
    1
    2
    0
    1
        Hematocrit: <=0.37 v/v (Male); <=0.32 v/v (Female)
    1
    0
    1
    1
    1
    1
        Hematocrit: >=0.55 v/v (Male); >=0.5 v/v (Female)
    0
    0
    0
    0
    1
    0
        Platelet Count: <100x10^9/L
    0
    0
    0
    0
    0
    0
        Platelet Count: >=700x10^9/L
    0
    0
    0
    0
    0
    0
        Erythrocyte Count: >=6x10^12/L
    0
    0
    0
    0
    1
    0
        Monocytes: >0.7x10^9/L
    1
    0
    1
    1
    0
    0
        Basophils: >0.1x10^9/L
    1
    0
    2
    1
    0
    0
        Leukocyte Count: <3x10^9/L (Non-Bk); <2x10^9/L(Bk)
    0
    0
    0
    0
    0
    0
        Leukocyte Count: >=16x10^9/L
    0
    0
    0
    0
    0
    0
        Neutrophils: <1.5x10^9/L (Non-Bk); <1x10^9/L (Bk)
    0
    0
    0
    0
    0
    0
        Lymphocytes: >4x10^9/L
    0
    1
    0
    0
    0
    0
        Eosinophils:>0.5x10^9/L or >ULN (ULN>=0.5x10^9/L)
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Change From Baseline in Urine Blood Urea Nitrogen (BUN) up to Last IMP Administration

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    End point title
    		 Change From Baseline in Urine Blood Urea Nitrogen (BUN) up to Last IMP Administration [5]
    End point description
    Last on-treatment (LOT) values were collected at or just prior to the last IMP administration. Results are based on the safety analysis set which included all participants who received at least 1 complete infusion of IMP.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1) and last on-treatment values (up to 454 weeks)
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint is descriptive in nature, no statistical analysis is provided.
    End point values
    		 Group 1: Avalglucosidase alfa 5 mg/kg Group 1: Avalglucosidase alfa 10 mg/kg Group 1: Avalglucosidase alfa 20 mg/kg Group 2: Avalglucosidase alfa 5 mg/kg Group 2: Avalglucosidase alfa 10 mg/kg Group 2: Avalglucosidase alfa 20 mg/kg
    Number of subjects analysed
    4
    3
    3
    4
    4
    6
    Units: millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    60.8 ( 121.0 )
    -17.6 ( 268.8 )
    179.5 ( 157.7 )
    72.9 ( 25.8 )
    37.1 ( 186.5 )
    118.8 ( 134.8 )
    No statistical analyses for this end point

    Primary: Change From Baseline in Urine Hyaline Casts up to Last IMP Administration

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    End point title
    		 Change From Baseline in Urine Hyaline Casts up to Last IMP Administration [6]
    End point description
    The LOT values were collected at or just prior to the last IMP administration. Results are based on the safety analysis set which included all participants who received at least 1 complete infusion of IMP. Here, 9999= Standard deviation could not be determined when only 1 participant was analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1) and last on-treatment values (up to 454 weeks)
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint is descriptive in nature, no statistical analysis is provided.
    End point values
    		 Group 1: Avalglucosidase alfa 5 mg/kg Group 1: Avalglucosidase alfa 10 mg/kg Group 1: Avalglucosidase alfa 20 mg/kg Group 2: Avalglucosidase alfa 5 mg/kg Group 2: Avalglucosidase alfa 10 mg/kg Group 2: Avalglucosidase alfa 20 mg/kg
    Number of subjects analysed
    0 [7]
    1
    0 [8]
    0 [9]
    0 [10]
    0 [11]
    Units: casts per low-power field (casts/lpf)
        arithmetic mean (standard deviation)
    ( )
    2.0 ( 9999 )
    ( )
    ( )
    ( )
    ( )
    Notes
    [7] - Only participants with data collected for LOT value are reported.
    [8] - Only participants with data collected for LOT value are reported.
    [9] - Only participants with data collected for LOT value are reported.
    [10] - Only participants with data collected for LOT value are reported.
    [11] - Only participants with data collected for LOT value are reported.
    No statistical analyses for this end point

    Primary: Change From Baseline in Urine Leukocytes [White Blood Cell (WBC)] up to Last IMP Administration

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    End point title
    		 Change From Baseline in Urine Leukocytes [White Blood Cell (WBC)] up to Last IMP Administration [12]
    End point description
    The LOT values were collected at or just prior to the last IMP administration. Results are based on the safety analysis set which included all participants who received at least 1 complete infusion of IMP. Here, 9999= Standard deviation could not be determined when only 1 participant was analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1) and last on-treatment values (up to 454 weeks)
    Notes
    [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint is descriptive in nature, no statistical analysis is provided.
    End point values
    		 Group 1: Avalglucosidase alfa 5 mg/kg Group 1: Avalglucosidase alfa 10 mg/kg Group 1: Avalglucosidase alfa 20 mg/kg Group 2: Avalglucosidase alfa 5 mg/kg Group 2: Avalglucosidase alfa 10 mg/kg Group 2: Avalglucosidase alfa 20 mg/kg
    Number of subjects analysed
    0 [13]
    1
    0 [14]
    0 [15]
    0 [16]
    0 [17]
    Units: WBC per high power field (WBC/ HPF)
        arithmetic mean (standard deviation)
    ( )
    -1.0 ( 9999 )
    ( )
    ( )
    ( )
    ( )
    Notes
    [13] - Only participants with data collected for LOT value are reported.
    [14] - Only participants with data collected for LOT value are reported.
    [15] - Only participants with data collected for LOT value are reported.
    [16] - Only participants with data collected for LOT value are reported.
    [17] - Only participants with data collected for LOT value are reported.
    No statistical analyses for this end point

    Primary: Change From Baseline in Urine Specific Gravity up to Last IMP Administration

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    End point title
    		 Change From Baseline in Urine Specific Gravity up to Last IMP Administration [18]
    End point description
    The LOT values were collected at or just prior to the last IMP administration. Results are based on the safety analysis set which included all participants who received at least 1 complete infusion of IMP. Only participants with data collected for LOT value are reported.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1) and last on-treatment values (up to 454 weeks)
    Notes
    [18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint is descriptive in nature, no statistical analysis is provided.
    End point values
    		 Group 1: Avalglucosidase alfa 5 mg/kg Group 1: Avalglucosidase alfa 10 mg/kg Group 1: Avalglucosidase alfa 20 mg/kg Group 2: Avalglucosidase alfa 5 mg/kg Group 2: Avalglucosidase alfa 10 mg/kg Group 2: Avalglucosidase alfa 20 mg/kg
    Number of subjects analysed
    3
    3
    3
    2
    3
    3
    Units: ratio
        arithmetic mean (standard deviation)
    0.0 ( 0.0 )
    0.0 ( 0.0 )
    0.0 ( 0.0 )
    0.0 ( 0.1 )
    0.0 ( 0.0 )
    0.0 ( 0.0 )
    No statistical analyses for this end point

    Primary: Change From Baseline in Urine pH up to Last IMP Administration

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    End point title
    		 Change From Baseline in Urine pH up to Last IMP Administration [19]
    End point description
    The LOT values were collected at or just prior to the last IMP administration. Results are based on the safety analysis set which included all participants who received at least 1 complete infusion of IMP. Only participants with data collected for LOT value are reported.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1) and last on-treatment values (up to 454 weeks)
    Notes
    [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint is descriptive in nature, no statistical analysis is provided.
    End point values
    		 Group 1: Avalglucosidase alfa 5 mg/kg Group 1: Avalglucosidase alfa 10 mg/kg Group 1: Avalglucosidase alfa 20 mg/kg Group 2: Avalglucosidase alfa 5 mg/kg Group 2: Avalglucosidase alfa 10 mg/kg Group 2: Avalglucosidase alfa 20 mg/kg
    Number of subjects analysed
    3
    3
    3
    2
    3
    3
    Units: pH score
        arithmetic mean (standard deviation)
    -0.4 ( 1.3 )
    0.2 ( 1.0 )
    -0.3 ( 1.1 )
    0.1 ( 0.5 )
    -0.8 ( 0.4 )
    -0.3 ( 0.9 )
    No statistical analyses for this end point

    Primary: Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities

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    End point title
    		 Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities [20]
    End point description
    Participants vital signs were examined to determine the abnormalities. Vital signs included heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP). Results are based on the safety analysis set which included all participants who received at least 1 complete infusion of IMP. Here, mmHg= millimeter of mercury and bpm= beats/minute.
    End point type
    Primary
    End point timeframe
    From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
    Notes
    [20] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint is descriptive in nature, no statistical analysis is provided.
    End point values
    		 Group 1: Avalglucosidase alfa 5 mg/kg Group 1: Avalglucosidase alfa 10 mg/kg Group 1: Avalglucosidase alfa 20 mg/kg Group 2: Avalglucosidase alfa 5 mg/kg Group 2: Avalglucosidase alfa 10 mg/kg Group 2: Avalglucosidase alfa 20 mg/kg
    Number of subjects analysed
    4
    3
    3
    4
    4
    6
    Units: participants
        SBP:<=95 mmHg and decrease from baseline >=20 mmHg
    2
    2
    2
    2
    3
    2
        SBP:>=160 mmHg and increase from baseline >=20mmHg
    2
    0
    1
    2
    0
    3
        DBP:<=45 mmHg and decrease from baseline >=10 mmHg
    2
    0
    0
    2
    0
    2
        DBP:>=110 mmHg and increase from baseline >=10mmHg
    2
    0
    0
    0
    0
    2
        HR:<=50 bpm and decrease from baseline >=20 bpm
    1
    0
    1
    0
    1
    0
        HR:>=120 bpm and increase from baseline >=20 bpm
    2
    1
    2
    2
    2
    4
    No statistical analyses for this end point

    Primary: Number of Participants With Body Weight Increased/Decreased

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    End point title
    		 Number of Participants With Body Weight Increased/Decreased [21]
    End point description
    Body weight was measured in kilograms and collected in the electronic case report forms every 3 months throughout the duration of the study, as well as at the end of study visit. Results are based on the safety analysis set which included all participants who received at least 1 complete infusion of IMP.
    End point type
    Primary
    End point timeframe
    From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
    Notes
    [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint is descriptive in nature, no statistical analysis is provided.
    End point values
    		 Group 1: Avalglucosidase alfa 5 mg/kg Group 1: Avalglucosidase alfa 10 mg/kg Group 1: Avalglucosidase alfa 20 mg/kg Group 2: Avalglucosidase alfa 5 mg/kg Group 2: Avalglucosidase alfa 10 mg/kg Group 2: Avalglucosidase alfa 20 mg/kg
    Number of subjects analysed
    4
    3
    3
    4
    4
    6
    Units: participants
    1
    0
    0
    1
    0
    2
    No statistical analyses for this end point

    Primary: Number of Participants With Potentially Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities

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    End point title
    		 Number of Participants With Potentially Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities [22]
    End point description
    Standard 12-lead ECGs were recorded after at least 15 minutes in the supine position using an electrocardiographic device. The following were assessed: heart rate, rhythm, interval between the peaks of successive QRS complexes (RR), interval from the beginning of the P wave until the beginning of the QRS complex (PR), interval from start of the Q wave to the end of the S wave (QRS), interval between the start of the Q wave and the end of the T wave (QT), QT interval corrected for heart rate (QTc) automatic correction evaluation (by the ECG device), QRS axis, R voltage V6, voltage V1, left ventricular hypertrophy criteria, right ventricular hypertrophy criteria, repolarization charges, and overall cardiac impression for each participant. Results are based on the safety analysis set which included all participants who received at least 1 complete infusion of IMP. Here, BCF= Bazett's Correction Formula and FCF= Fridericia's Correction Formula.
    End point type
    Primary
    End point timeframe
    From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
    Notes
    [22] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint is descriptive in nature, no statistical analysis is provided.
    End point values
    		 Group 1: Avalglucosidase alfa 5 mg/kg Group 1: Avalglucosidase alfa 10 mg/kg Group 1: Avalglucosidase alfa 20 mg/kg Group 2: Avalglucosidase alfa 5 mg/kg Group 2: Avalglucosidase alfa 10 mg/kg Group 2: Avalglucosidase alfa 20 mg/kg
    Number of subjects analysed
    4
    3
    3
    4
    4
    6
    Units: participants
        HR: <50 bpm
    1
    0
    0
    0
    1
    0
        HR: <50 bpm and decrease from baseline >=20 bpm
    0
    0
    0
    0
    0
    0
        HR: <40 bpm
    0
    0
    0
    0
    0
    0
        HR: <40 bpm and decrease from baseline >=20 bpm
    0
    0
    0
    0
    0
    0
        HR: <30 bpm
    0
    0
    0
    0
    0
    0
        HR: <30 bpm and decrease from baseline >=20 bpm
    0
    0
    0
    0
    0
    0
        HR: >90 bpm
    0
    2
    0
    0
    0
    2
        HR: >90 bpm and increase from baseline >=20 bpm
    0
    2
    0
    0
    0
    0
        HR: >100 bpm
    0
    0
    1
    0
    0
    0
        HR: >100 bpm and increase from baseline >=20 bpm
    0
    0
    0
    0
    0
    0
        HR: >120 bpm
    0
    0
    0
    0
    0
    0
        HR: >120 bpm and increase from baseline >=20 bpm
    0
    0
    0
    0
    0
    0
        PR Duration: > 200 millisecond (msec)
    0
    1
    1
    0
    0
    1
        PR Duration: >200 msec and baseline increase >=25%
    0
    1
    0
    0
    0
    0
        PR Duration: >220 msec
    0
    0
    0
    1
    0
    0
        PR Duration: >220 msec and baseline increase >=25%
    0
    0
    0
    1
    0
    0
        PR Duration: >240 msec
    0
    0
    0
    0
    0
    0
        PR Duration: >240 msec and baseline increase >=25%
    0
    0
    0
    0
    0
    0
        QRS Duration: >110 msec
    0
    0
    1
    0
    3
    4
        QRS Duration:>110 msec and baseline increase >=25%
    0
    0
    0
    0
    0
    0
        QRS Duration: >120 msec
    0
    1
    1
    1
    0
    0
        QRS Duration:>120 msec and baseline increase >=25%
    0
    0
    1
    0
    0
    0
        QTcB - BCF: >450 msec
    1
    1
    1
    2
    1
    3
        QTcB - BCF: >480 msec
    0
    0
    0
    0
    0
    0
        QTcB - BCF: >500 msec
    0
    0
    0
    0
    0
    0
        QTcB - BCF: Baseline increase (30-60) msec
    0
    2
    1
    1
    1
    4
        QTcB - BCF: Baseline increase >60 msec
    0
    0
    0
    0
    1
    0
        QTcF - FCF: >450 msec
    0
    1
    0
    1
    1
    0
        QTcF - FCF: >480 msec
    0
    0
    0
    0
    0
    0
        QTcF - FCF: >500 msec
    0
    0
    0
    0
    0
    0
        QTcF - FCF: Baseline increase (30-60) msec
    0
    1
    0
    0
    0
    1
        QTcF - FCF: Baseline increase >60 msec
    0
    0
    0
    0
    1
    0
    No statistical analyses for this end point

    Primary: Number of Participants With Antidrug Antibodies (ADA) Status, Positive or Negative

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    End point title
    		 Number of Participants With Antidrug Antibodies (ADA) Status, Positive or Negative [23]
    End point description
    ADA negative was defined as ADAs are not detected (that is, negative in screening assay or reactive in screening but negative in confirmatory assay). ADA positive was defined as ADA was detected (that is, an assay signal equal to or greater than the cut-point in the screening assay and was tested positive in the confirmatory assay). Results are based on the Pharmacodynamic (PD) analysis set which included enrolled participants without any critical deviations related to IMP administration, and for whom any PD data were available.
    End point type
    Primary
    End point timeframe
    From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
    Notes
    [23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint is descriptive in nature, no statistical analysis is provided.
    End point values
    		 Group 1: Avalglucosidase alfa 5 mg/kg Group 1: Avalglucosidase alfa 10 mg/kg Group 1: Avalglucosidase alfa 20 mg/kg Group 2: Avalglucosidase alfa 5 mg/kg Group 2: Avalglucosidase alfa 10 mg/kg Group 2: Avalglucosidase alfa 20 mg/kg
    Number of subjects analysed
    4
    3
    3
    4
    4
    6
    Units: participants
        ADA negative
    0
    1
    0
    1
    1
    3
        ADA positive at baseline
    0
    0
    0
    1
    3
    1
        ADA positive post-baseline
    4
    2
    3
    2
    0
    2
    No statistical analyses for this end point

    Primary: Maximum Observed Plasma Concentration (Cmax) of Avalglucosidase Alfa

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    End point title
    		 Maximum Observed Plasma Concentration (Cmax) of Avalglucosidase Alfa [24]
    End point description
    Cmax was defined as maximum plasma concentration observed. The non-compartmental pharmacokinetic (PK) analysis was performed. Results are based on the PK analysis set which included enrolled participants without any critical deviations related to IMP administration, and for whom any PK data were available.
    End point type
    Primary
    End point timeframe
    Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
    Notes
    [24] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint is descriptive in nature, no statistical analysis is provided.
    End point values
    		 Group 1: Avalglucosidase Alfa Group 2: Avalglucosidase Alfa
    Number of subjects analysed
    4
    5
    Units: microgram per milliliter (mcg/mL)
        geometric mean (geometric coefficient of variation)
    269 ( 16 )
    234 ( 24 )
    No statistical analyses for this end point

    Primary: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Real Time (AUClast) of Avalglucosidase Alfa

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    End point title
    		 Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Real Time (AUClast) of Avalglucosidase Alfa [25]
    End point description
    AUClast was calculated using the trapezoidal method from time zero to the real time. The non-compartmental PK analysis was performed. Results are based on the PK analysis set which included enrolled participants without any critical deviations related to IMP administration, and for whom any PK data were available. Only participants who contributed to the analysis for this outcome measure are reported.
    End point type
    Primary
    End point timeframe
    Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
    Notes
    [25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint is descriptive in nature, no statistical analysis is provided.
    End point values
    		 Group 1: Avalglucosidase Alfa Group 2: Avalglucosidase Alfa
    Number of subjects analysed
    4
    4
    Units: hour*mcg/mL
        geometric mean (geometric coefficient of variation)
    1350 ( 24 )
    1290 ( 21 )
    No statistical analyses for this end point

    Primary: Time Corresponding to the Last Concentration (Tlast) of Avalglucosidase Alfa

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    End point title
    		 Time Corresponding to the Last Concentration (Tlast) of Avalglucosidase Alfa [26]
    End point description
    Tlast was defined as time corresponding to the last concentration above the limit of quantification, Clast. The non-compartmental PK analysis was performed. Results are based on the PK analysis set which included enrolled participants without any critical deviations related to IMP administration, and for whom any PK data were available. Only participants who contributed to the analysis for this outcome measure are reported.
    End point type
    Primary
    End point timeframe
    Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
    Notes
    [26] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint is descriptive in nature, no statistical analysis is provided.
    End point values
    		 Group 1: Avalglucosidase Alfa Group 2: Avalglucosidase Alfa
    Number of subjects analysed
    4
    4
    Units: hour
        median (full range (min-max))
    25.84 (25.65 to 27.73)
    27.6 (7.5 to 29.5)
    No statistical analyses for this end point

    Primary: Terminal Half-Life (t1/2z) of Avalglucosidase Alfa

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    End point title
    		 Terminal Half-Life (t1/2z) of Avalglucosidase Alfa [27]
    End point description
    t1/2z was calculated according to the following equation: t1/2z = 0.693/λz. Where, λz is the slope of the regression line of the terminal phase of the plasma concentration versus time curve. Half-life was calculated by taking the regression of at least 3 points. The non-compartmental PK analysis was performed. Results are based on the PK analysis set which included enrolled participants without any critical deviations related to IMP administration, and for whom any PK data were available. Only participants who contributed to the analysis for this outcome measure are reported.
    End point type
    Primary
    End point timeframe
    Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
    Notes
    [27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint is descriptive in nature, no statistical analysis is provided.
    End point values
    		 Group 1: Avalglucosidase Alfa Group 2: Avalglucosidase Alfa
    Number of subjects analysed
    4
    4
    Units: hour
        geometric mean (geometric coefficient of variation)
    1.62 ( 9 )
    1.79 ( 8 )
    No statistical analyses for this end point

    Primary: Apparent Total Body Clearance Steady-State (CLss) of Avalglucosidase Alfa

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    End point title
    		 Apparent Total Body Clearance Steady-State (CLss) of Avalglucosidase Alfa [28]
    End point description
    CLss was calculated using the following equation: CLss= dose/AUC. The non-compartmental PK analysis was performed. Results are based on the PK analysis set which included enrolled participants without any critical deviations related to IMP administration, and for whom any PK data were available. Only participants who contributed to the analysis for this outcome measure are reported.
    End point type
    Primary
    End point timeframe
    Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
    Notes
    [28] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint is descriptive in nature, no statistical analysis is provided.
    End point values
    		 Group 1: Avalglucosidase Alfa Group 2: Avalglucosidase Alfa
    Number of subjects analysed
    4
    3
    Units: liter/hour
        geometric mean (geometric coefficient of variation)
    0.90 ( 24 )
    1.06 ( 12 )
    No statistical analyses for this end point

    Primary: Apparent Volume of Distribution Steady-State (Vss) of Avalglucosidase Alfa

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    End point title
    		 Apparent Volume of Distribution Steady-State (Vss) of Avalglucosidase Alfa [29]
    End point description
    Vss was calculated using the following equation: Vz= CLss/λz. The non-compartmental PK analysis was performed. Results are based on the PK analysis set which included enrolled participants without any critical deviations related to IMP administration, and for whom any PK data were available. Only participants who contributed to the analysis for this outcome measure are reported.
    End point type
    Primary
    End point timeframe
    Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
    Notes
    [29] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint is descriptive in nature, no statistical analysis is provided.
    End point values
    		 Group 1: Avalglucosidase Alfa Group 2: Avalglucosidase Alfa
    Number of subjects analysed
    4
    3
    Units: liter
        geometric mean (geometric coefficient of variation)
    3.04 ( 13 )
    3.8 ( 24 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Cross-Sectional Area (CSA) of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442

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    End point title
    		 Change From Baseline in Cross-Sectional Area (CSA) of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
    End point description
    Skeletal muscle MRI performed prior to the muscle needle or open biopsy procedure using both qualitative (T1) and quantitative (T2, dixon) modalities to assess disease severity and detect treatment effects. The T1 weighted axial data was analyzed using the mercuri scale, which determines degree of intact muscle and fatty replacement, providing a qualitative measure of overall disease severity. Trophicity changes were evaluated for 5 muscle groups, including upper leg muscles [quadriceps (Q), hamstring (H)] and lower leg muscles [triceps (TS), extensors (LE), fibularis (F)]. The measured area of each muscle group, CSA was provided. Results are based on the PD analysis set. Here, n= number of participants analyzed at specific time points, 9999= no participants were analyzed, 99999= standard deviation could not be determined when only 1 participant was analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Weeks 104 and 442
    End point values
    		 Group 1: Avalglucosidase alfa 5 mg/kg Group 1: Avalglucosidase alfa 10 mg/kg Group 1: Avalglucosidase alfa 20 mg/kg Group 2: Avalglucosidase alfa 5 mg/kg Group 2: Avalglucosidase alfa 10 mg/kg Group 2: Avalglucosidase alfa 20 mg/kg
    Number of subjects analysed
    0 [30]
    0 [31]
    2
    3
    2
    3
    Units: millimeter square (mm^2)
    arithmetic mean (standard deviation)
        Week 104: CSA - F muscle (n=0,0,2,3,2,3)
    ( )
    ( )
    57.4 ( 3.9 )
    -0.9 ( 46.9 )
    46.1 ( 81.2 )
    26.7 ( 40.0 )
        Week 104: CSA - H muscle (n=0,0,2,3,2,3)
    ( )
    ( )
    123.0 ( 254.7 )
    -135.7 ( 138.7 )
    70.6 ( 368.1 )
    215.2 ( 126.1 )
        Week 104: CSA - LE muscle (n=0,0,2,3,2,3)
    ( )
    ( )
    23.2 ( 60.2 )
    23.1 ( 19.1 )
    107.9 ( 145.0 )
    39.1 ( 26.6 )
        Week 104: CSA - Q muscle (n=0,0,2,3,2,3)
    ( )
    ( )
    303.3 ( 49.5 )
    -27.6 ( 45.8 )
    134.0 ( 569.4 )
    193.3 ( 103.3 )
        Week 104: CSA - TS muscle (n=0,0,2,3,2,3)
    ( )
    ( )
    283.6 ( 123.7 )
    -310.0 ( 383.2 )
    -3.5 ( 334.6 )
    226.0 ( 172.3 )
        Week 442: CSA - F muscle (n=0,0,0,0,1,1)
    ( )
    ( )
    9999 ( 9999 )
    9999 ( 9999 )
    -41.8 ( 99999 )
    -55.6 ( 99999 )
        Week 442: CSA - H muscle (n=0,0,0,0,1,1)
    ( )
    ( )
    9999 ( 9999 )
    9999 ( 9999 )
    -461.1 ( 99999 )
    -30.2 ( 99999 )
        Week 442: CSA - LE muscle (n=0,0,0,0,1,1)
    ( )
    ( )
    9999 ( 9999 )
    9999 ( 9999 )
    -102.7 ( 99999 )
    -68.9 ( 99999 )
        Week 442: CSA - Q muscle (n=0,0,0,0,1,1)
    ( )
    ( )
    9999 ( 9999 )
    9999 ( 9999 )
    -644.7 ( 99999 )
    19.8 ( 99999 )
        Week 442: CSA - TS muscle (n=0,0,0,0,1,1)
    ( )
    ( )
    9999 ( 9999 )
    9999 ( 9999 )
    -220.9 ( 99999 )
    -82.3 ( 99999 )
    Notes
    [30] - No participants were analyzed.
    [31] - No participants were analyzed.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Dixon Fat Fraction of Skeletal Muscle Magnetic Resonance Imaging Up to Week 442

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    End point title
    		 Change From Baseline in Dixon Fat Fraction of Skeletal Muscle Magnetic Resonance Imaging Up to Week 442
    End point description
    Skeletal muscle MRI performed prior to the muscle needle or open biopsy procedure using both qualitative (T1) and quantitative (T2, dixon) modalities to assess disease severity and detect treatment effects. The T1 weighted axial data was analyzed using the mercuri scale, which determines degree of intact muscle and fatty replacement, providing a qualitative measure of overall disease severity. Trophicity changes were evaluated for 5 muscle groups, including the upper leg muscles (Q and H) and the lower leg muscles (TS, LE and F). Three-point dixon imaging provided quantification of fat content in muscles [fat fraction (FF)]. Results are based on the PD analysis set. Here, n= number of participants analyzed at specific time points, 9999= no participants were analyzed, 99999= standard deviation could not be determined when only 1 participant was analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Weeks 104 and 442
    End point values
    		 Group 1: Avalglucosidase alfa 5 mg/kg Group 1: Avalglucosidase alfa 10 mg/kg Group 1: Avalglucosidase alfa 20 mg/kg Group 2: Avalglucosidase alfa 5 mg/kg Group 2: Avalglucosidase alfa 10 mg/kg Group 2: Avalglucosidase alfa 20 mg/kg
    Number of subjects analysed
    0 [32]
    0 [33]
    2
    3
    1
    3
    Units: percentage (%)
    arithmetic mean (standard deviation)
        Week 104: DFF - F muscle (n=0,0,2,3,1,3)
    ( )
    ( )
    0.9 ( 0.1 )
    1.4 ( 2.2 )
    -0.7 ( 99999 )
    0.3 ( 1.1 )
        Week 104: DFF - H muscle (n=0,0,2,3,1,3)
    ( )
    ( )
    5.7 ( 3.3 )
    -0.2 ( 2.6 )
    -0.3 ( 99999 )
    3.4 ( 3.9 )
        Week 104: DFF - LE muscle (n=0,0,2,3,1,3)
    ( )
    ( )
    0.9 ( 0.1 )
    0.8 ( 2.2 )
    -0.3 ( 99999 )
    -0.2 ( 1.3 )
        Week 104: DFF - Q muscle (n=0,0,2,3,1,3)
    ( )
    ( )
    2.3 ( 1.4 )
    -0.5 ( 2.3 )
    0.2 ( 99999 )
    2.4 ( 3.6 )
        Week 104: DFF - TS muscle (n=0,0,2,3,1,3)
    ( )
    ( )
    0.4 ( 0.3 )
    1.4 ( 1.7 )
    -0.3 ( 99999 )
    0.9 ( 0.5 )
        Week 442: DFF - F muscle (n=0,0,0,0,1,1)
    ( )
    ( )
    9999 ( 9999 )
    9999 ( 9999 )
    2.1 ( 99999 )
    0.8 ( 99999 )
        Week 442: DFF - H muscle (n=0,0,0,0,1,1)
    ( )
    ( )
    9999 ( 9999 )
    9999 ( 9999 )
    10.1 ( 99999 )
    0.6 ( 99999 )
        Week 442: DFF - LE muscle (n=0,0,0,0,1,1)
    ( )
    ( )
    9999 ( 9999 )
    9999 ( 9999 )
    1.6 ( 99999 )
    -0.0 ( 99999 )
        Week 442: DFF - Q muscle (n=0,0,0,0,1,1)
    ( )
    ( )
    9999 ( 9999 )
    9999 ( 9999 )
    9.7 ( 99999 )
    0.8 ( 99999 )
        Week 442: DFF - TS muscle (n=0,0,0,0,1,1)
    ( )
    ( )
    9999 ( 9999 )
    9999 ( 9999 )
    1.8 ( 99999 )
    0.5 ( 99999 )
    Notes
    [32] - No participants were analyzed.
    [33] - No participants were analyzed.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Index of Real Muscle Mass (IRMM) of Skeletal Muscle Magnetic Resonance Imaging Up to Week 442

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    End point title
    		 Change From Baseline in Index of Real Muscle Mass (IRMM) of Skeletal Muscle Magnetic Resonance Imaging Up to Week 442
    End point description
    Skeletal muscle MRI performed prior to muscle needle or open biopsy procedure using both qualitative (T1) and quantitative (T2, dixon) modalities to assess disease severity and detect treatment effects. The T1 weighted axial data was analyzed using the mercuri scale, which determines degree of intact muscle and fatty replacement, providing a qualitative measure of overall disease severity. Trophicity changes were evaluated for 5 muscle groups, including upper leg muscles (Q and H) and lower leg muscles (TS, LE and F). The FF was combined with CSA measurements trophicity to provide an IRMM (that is, IRMM= CSA x [1 – FF]). A negative change from baseline value indicates muscle loss (worse outcome) and a positive change from baseline value indicates muscle gain (better outcome). The PD analysis set. Here, n= number of participants analyzed at specific time points, 9999= no participants were analyzed, 99999= standard deviation could not be determined when only 1 participant was analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Weeks 104 and 442
    End point values
    		 Group 1: Avalglucosidase alfa 5 mg/kg Group 1: Avalglucosidase alfa 10 mg/kg Group 1: Avalglucosidase alfa 20 mg/kg Group 2: Avalglucosidase alfa 5 mg/kg Group 2: Avalglucosidase alfa 10 mg/kg Group 2: Avalglucosidase alfa 20 mg/kg
    Number of subjects analysed
    0 [34]
    0 [35]
    2
    3
    1
    3
    Units: mm^2
    arithmetic mean (standard deviation)
        Week 104: IRMM - F muscle (n=0,0,2,3,1,3)
    ( )
    ( )
    44.8 ( 8.3 )
    -13.8 ( 40.4 )
    -5.8 ( 99999 )
    21.8 ( 41.6 )
        Week 104: IRMM - H muscle (n=0,0,2,3,1,3)
    ( )
    ( )
    -131.6 ( 77.0 )
    -100.9 ( 150.3 )
    -149.7 ( 99999 )
    49.2 ( 139.0 )
        Week 104: IRMM - LE muscle (n=0,0,2,3,1,3)
    ( )
    ( )
    12.4 ( 59.9 )
    9.8 ( 34.2 )
    7.5 ( 99999 )
    34.9 ( 33.2 )
        Week 104: IRMM - Q muscle (n=0,0,2,3,1,3)
    ( )
    ( )
    149.2 ( 135.2 )
    -9.4 ( 65.9 )
    -256.0 ( 99999 )
    120.7 ( 166.3 )
        Week 104: IRMM - TS muscle (n=0,0,2,3,1,3)
    ( )
    ( )
    236.8 ( 122.2 )
    -299.6 ( 402.6 )
    -210.5 ( 99999 )
    181.4 ( 143.7 )
        Week 442: IRMM - F muscle (n=0,0,0,0,1,1)
    ( )
    ( )
    9999 ( 9999 )
    9999 ( 9999 )
    -53.4 ( 99999 )
    -54.9 ( 99999 )
        Week 442: IRMM - H muscle (n=0,0,0,0,1,1)
    ( )
    ( )
    9999 ( 9999 )
    9999 ( 9999 )
    -412.7 ( 99999 )
    -44.0 ( 99999 )
        Week 442: IRMM - LE muscle (n=0,0,0,0,1,1)
    ( )
    ( )
    9999 ( 9999 )
    9999 ( 9999 )
    -109.6 ( 99999 )
    -64.9 ( 99999 )
        Week 442: IRMM - Q muscle (n=0,0,0,0,1,1)
    ( )
    ( )
    9999 ( 9999 )
    9999 ( 9999 )
    -1085.4 ( 99999 )
    -21.5 ( 99999 )
        Week 442: IRMM - TS muscle (n=0,0,0,0,1,1)
    ( )
    ( )
    9999 ( 9999 )
    9999 ( 9999 )
    -288.6 ( 99999 )
    -85.1 ( 99999 )
    Notes
    [34] - No participants were analyzed.
    [35] - No participants were analyzed.
    No statistical analyses for this end point

    Secondary: Change From Baseline in T2 of Skeletal Muscle Magnetic Resonance Imaging Up to Week 442

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    End point title
    		 Change From Baseline in T2 of Skeletal Muscle Magnetic Resonance Imaging Up to Week 442
    End point description
    Skeletal muscle MRI performed prior to the muscle needle or open biopsy procedure using both qualitative (T1) and quantitative (T2, dixon) modalities to assess disease severity and detect treatment effects. The T1 weighted axial data was analyzed using the mercuri scale, which determines degree of intact muscle and fatty replacement, providing a qualitative measure of overall disease severity. Trophicity changes were evaluated for 5 muscle groups, including the upper leg muscles (Q and H) and the lower leg muscles (TS, LE and F). The T2 multi-slice multi-spin echo and B1 mapping provided a quantitative measure of disease activity (edema, inflammation) within muscles. Results are based on the PD analysis set. Here, n= number of participants analyzed at specific time points, 9999= no participants were analyzed, 99999= standard deviation could not be determined when only 1 participant was analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Weeks 104 and 442
    End point values
    		 Group 1: Avalglucosidase alfa 5 mg/kg Group 1: Avalglucosidase alfa 10 mg/kg Group 1: Avalglucosidase alfa 20 mg/kg Group 2: Avalglucosidase alfa 5 mg/kg Group 2: Avalglucosidase alfa 10 mg/kg Group 2: Avalglucosidase alfa 20 mg/kg
    Number of subjects analysed
    1
    0 [36]
    2
    3
    1
    3
    Units: milliseconds (ms)
    arithmetic mean (standard deviation)
        Week 104: T2 - F muscle (n=0,0,2,3,1,3)
    9999 ( 9999 )
    ( )
    -0.6 ( 0.6 )
    0.5 ( 2.4 )
    0.8 ( 99999 )
    0.0 ( 0.6 )
        Week 104: T2 - H muscle (n=0,0,1,3,1,3)
    9999 ( 9999 )
    ( )
    0.7 ( 99999 )
    1.6 ( 3.2 )
    -1.4 ( 99999 )
    0.2 ( 0.7 )
        Week 104: T2 - LE muscle (n=0,0,2,3,1,3)
    9999 ( 9999 )
    ( )
    -0.8 ( 1.6 )
    2.0 ( 2.2 )
    1.7 ( 99999 )
    -0.3 ( 0.7 )
        Week 104: T2 - Q muscle (n=0,0,2,3,1,3)
    9999 ( 9999 )
    ( )
    0.8 ( 1.0 )
    0.5 ( 2.7 )
    -1.3 ( 99999 )
    1.0 ( 0.6 )
        Week 104: T2 - TS muscle (n=0,0,2,3,1,3)
    9999 ( 9999 )
    ( )
    -0.3 ( 0.3 )
    0.5 ( 1.7 )
    -0.9 ( 99999 )
    0.4 ( 0.6 )
        Week 442: T2 - F muscle (n=1,0,0,0,1,1)
    -4.1 ( 99999 )
    ( )
    9999 ( 9999 )
    9999 ( 9999 )
    0.7 ( 99999 )
    0.1 ( 99999 )
        Week 442: T2 - H muscle (n=1,0,0,0,1,1)
    -6.0 ( 99999 )
    ( )
    9999 ( 9999 )
    9999 ( 9999 )
    -9.1 ( 99999 )
    2.2 ( 99999 )
        Week 442: T2 - LE muscle (n=1,0,0,0,1,1)
    -2.5 ( 99999 )
    ( )
    9999 ( 9999 )
    9999 ( 9999 )
    1.4 ( 99999 )
    0.6 ( 99999 )
        Week 442: T2 - Q muscle (n=1,0,0,0,1,1)
    -0.5 ( 99999 )
    ( )
    9999 ( 9999 )
    9999 ( 9999 )
    1.0 ( 99999 )
    3.4 ( 99999 )
        Week 442: T2 - TS muscle (n=1,0,0,0,1,1)
    -3.5 ( 99999 )
    ( )
    9999 ( 9999 )
    9999 ( 9999 )
    1.8 ( 99999 )
    -0.0 ( 99999 )
    Notes
    [36] - No participants were analyzed.
    No statistical analyses for this end point

    Secondary: Change From Baseline in T2 With B1 of Skeletal Muscle Magnetic Resonance Imaging Up to Week 442

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    End point title
    		 Change From Baseline in T2 With B1 of Skeletal Muscle Magnetic Resonance Imaging Up to Week 442
    End point description
    Skeletal muscle MRI performed prior to the muscle needle or open biopsy procedure using both qualitative (T1) and quantitative (T2, dixon) modalities to assess disease severity and detect treatment effects. The T1 weighted axial data was analyzed using the mercuri scale, which determines degree of intact muscle and fatty replacement, providing a qualitative measure of overall disease severity. Trophicity changes were evaluated for 5 muscle groups, including the upper leg muscles (Q and H) and the lower leg muscles (TS, LE and F). The T2 multi-slice multi-spin echo and B1 mapping provided a quantitative measure of disease activity (edema, inflammation) within muscles. Results are based on the PD analysis set. Here, n= number of participants analyzed at specific time points, 9999= no participants were analyzed, 99999= standard deviation could not be determined when only 1 participant was analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Weeks 104 and 442
    End point values
    		 Group 1: Avalglucosidase alfa 5 mg/kg Group 1: Avalglucosidase alfa 10 mg/kg Group 1: Avalglucosidase alfa 20 mg/kg Group 2: Avalglucosidase alfa 5 mg/kg Group 2: Avalglucosidase alfa 10 mg/kg Group 2: Avalglucosidase alfa 20 mg/kg
    Number of subjects analysed
    1
    0 [37]
    2
    3
    1
    2
    Units: ms
    arithmetic mean (standard deviation)
        Week 104: T2 with B1 - F muscle (n=0,0,2,3,1,1)
    9999 ( 9999 )
    ( )
    -0.5 ( 0.7 )
    0.5 ( 2.2 )
    1.4 ( 99999 )
    0.3 ( 99999 )
        Week 104: T2 with B1 - H muscle (n=0,0,1,3,1,2)
    9999 ( 9999 )
    ( )
    -0.4 ( 99999 )
    2.3 ( 4.6 )
    -2.3 ( 99999 )
    -0.4 ( 1.6 )
        Week 104: T2 with B1 - LE muscle (n=0,0,2,3,1,1)
    9999 ( 9999 )
    ( )
    -0.6 ( 1.9 )
    2.0 ( 2.2 )
    0.7 ( 99999 )
    -2.1 ( 99999 )
        Week 104: T2 with B1 - Q muscle (n=0,0,2,3,1,2)
    9999 ( 9999 )
    ( )
    0.9 ( 0.7 )
    0.7 ( 2.8 )
    -1.4 ( 99999 )
    1.6 ( 0.6 )
        Week 104: T2 with B1 - TS muscle (n=0,0,2,3,1,1)
    9999 ( 9999 )
    ( )
    -0.3 ( 0.4 )
    0.1 ( 1.2 )
    -1.3 ( 99999 )
    0.5 ( 99999 )
        Week 442: T2 with B1 - F muscle (n=1,0,0,0,0,0)
    -4.1 ( 99999 )
    ( )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
        Week 442: T2 with B1 - LE muscle (n=1,0,0,0,0,0)
    -3.6 ( 99999 )
    ( )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
        Week 442: T2 with B1 - Q muscle (n=1,0,0,0,0,0)
    -0.3 ( 99999 )
    ( )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
        Week 442: T2 with B1 - TS muscle (n=1,0,0,0,0,0)
    -3.2 ( 99999 )
    ( )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    Notes
    [37] - No participants were analyzed.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Skeletal Muscle Biopsy Up to Week 312

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    End point title
    		 Change From Baseline in Skeletal Muscle Biopsy Up to Week 312
    End point description
    Skeletal muscle needle or open biopsy was performed on the lower extremity (quadriceps) muscle to assess glycogen content. The MRI appearance of the muscle was used to determine the level (axial slice position) that the biopsy procedure should target (avoiding fatty replaced tissue). Glycogen content was measured by histomorphometric analysis or severity grading to determine how effectively avalglucosidase alfa was able to remove glycogen from muscle. Results are based on the PD analysis set which included enrolled participants without any critical deviations related to IMP administration, and for whom any PD data were available. Here, n= number of participants analyzed at specific time points, 9999= no participants were analyzed and 99999= standard deviation could not be determined when only 1 participant was analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Weeks 27, 104, 208, 260 and 312
    End point values
    		 Group 1: Avalglucosidase alfa 5 mg/kg Group 1: Avalglucosidase alfa 10 mg/kg Group 1: Avalglucosidase alfa 20 mg/kg Group 2: Avalglucosidase alfa 5 mg/kg Group 2: Avalglucosidase alfa 10 mg/kg Group 2: Avalglucosidase alfa 20 mg/kg
    Number of subjects analysed
    4
    3
    3
    4
    4
    6
    Units: percentage of glycogen
    arithmetic mean (standard deviation)
        Left quadriceps muscle: Week 27 (n=1,0,2,3,1,3)
    0.8 ( 99999 )
    9999 ( 9999 )
    0.9 ( 0.1 )
    -3.6 ( 6.4 )
    0.5 ( 99999 )
    -0.4 ( 0.4 )
        Left quadriceps muscle: Week 104 (n=0,0,0,2,0,0)
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    -4.8 ( 9.9 )
    9999 ( 9999 )
    9999 ( 9999 )
        Left quadriceps muscle: Week 260 (n=0,0,0,1,0,0)
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    -4.3 ( 99999 )
    9999 ( 9999 )
    9999 ( 9999 )
        Right quadriceps muscle: Week 27 (n=3,2,1,0,2,0)
    -1.7 ( 3.3 )
    0.5 ( 1.5 )
    -1.1 ( 99999 )
    9999 ( 9999 )
    2.0 ( 1.0 )
    9999 ( 9999 )
        Right quadriceps muscle: Week 104 (n=0,0,0,0,1,0)
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    -2.8 ( 99999 )
    9999 ( 9999 )
        Right quadriceps muscle: Week 208 (n=0,0,0,0,1,0)
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    -3.8 ( 99999 )
    9999 ( 9999 )
        Right quadriceps muscle: Week 312 (n=0,0,0,0,1,0)
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    -5.4 ( 99999 )
    9999 ( 9999 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Urinary Glucose Tetrasaccharide (Hex4) Level Up to Week 442

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    End point title
    		 Change From Baseline in Urinary Glucose Tetrasaccharide (Hex4) Level Up to Week 442
    End point description
    The Hex4, a tetraglucose oligomer, has been shown to be elevated in the urine of participants with Pompe disease. Hence, determination of Hex4 levels may be a means by which the efficacy of treatments were monitored. Urine samples were collected prior to IMP infusion for the assessment of urinary Hex4 concentrations. Results are based on the PD analysis set which included enrolled participants without any critical deviations related to IMP administration, and for whom any PD data were available. Here, n= number of participants analyzed at specific time points, 9999= no participants were analyzed and 99999= standard deviation could not be determined when only 1 participant was analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Weeks 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 338, 364, 390, 416 and 442
    End point values
    		 Group 1: Avalglucosidase alfa 5 mg/kg Group 1: Avalglucosidase alfa 10 mg/kg Group 1: Avalglucosidase alfa 20 mg/kg Group 2: Avalglucosidase alfa 5 mg/kg Group 2: Avalglucosidase alfa 10 mg/kg Group 2: Avalglucosidase alfa 20 mg/kg
    Number of subjects analysed
    4
    3
    3
    4
    4
    6
    Units: mmol per mole
    arithmetic mean (standard deviation)
        Week 1 (n=1,0,0,0,0,0)
    0.5 ( 99999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
        Week 3 (n=3,3,3,4,4,6)
    -0.6 ( 0.2 )
    -1.9 ( 1.6 )
    -0.9 ( 0.5 )
    -0.9 ( 1.0 )
    -0.5 ( 1.1 )
    -0.2 ( 1.5 )
        Week 5 (n=4,3,3,4,4,5)
    -1.0 ( 0.5 )
    -0.2 ( 0.4 )
    -1.0 ( 1.1 )
    0.2 ( 0.7 )
    -0.5 ( 1.1 )
    -1.5 ( 2.0 )
        Week 7 (n=4,3,3,4,4,6)
    -1.2 ( 1.1 )
    -2.2 ( 1.7 )
    -0.6 ( 1.3 )
    -0.7 ( 0.8 )
    -0.3 ( 1.1 )
    -1.2 ( 2.3 )
        Week 9 (n=4,3,3,4,4,6)
    -0.6 ( 1.7 )
    -2.4 ( 3.2 )
    0.5 ( 0.7 )
    0.0 ( 1.3 )
    -0.7 ( 1.3 )
    -2.2 ( 2.7 )
        Week 11 (n=4,3,3,4,4,6)
    -0.1 ( 1.9 )
    -2.7 ( 2.6 )
    0.4 ( 1.0 )
    0.1 ( 0.8 )
    -0.5 ( 1.7 )
    -2.5 ( 3.3 )
        Week 13 (n=4,3,3,4,4,6)
    -1.3 ( 1.3 )
    -5.0 ( 3.4 )
    -1.6 ( 1.5 )
    0.5 ( 0.7 )
    -0.7 ( 1.3 )
    -2.7 ( 3.6 )
        Week 15 (n=4,3,3,4,4,6)
    -1.4 ( 0.5 )
    -6.2 ( 3.3 )
    -1.4 ( 0.5 )
    0.6 ( 1.5 )
    -1.0 ( 1.3 )
    -3.4 ( 4.8 )
        Week 17 (n=4,3,3,3,4,5)
    -1.0 ( 0.3 )
    -6.7 ( 2.1 )
    -1.5 ( 1.2 )
    -0.0 ( 1.4 )
    -0.9 ( 1.3 )
    -3.4 ( 4.5 )
        Week 19 (n=3,3,3,4,4,5)
    -2.3 ( 2.4 )
    -6.5 ( 2.5 )
    -1.6 ( 1.0 )
    0.3 ( 3.1 )
    -0.8 ( 1.8 )
    -4.0 ( 5.9 )
        Week 21 (n=3,3,3,4,4,5)
    -2.3 ( 2.1 )
    -6.5 ( 2.2 )
    -1.8 ( 1.3 )
    0.1 ( 2.2 )
    -0.8 ( 1.7 )
    -4.4 ( 5.6 )
        Week 23 (n=3,3,3,4,4,5)
    -1.7 ( 1.7 )
    -5.3 ( 1.3 )
    -0.7 ( 1.4 )
    0.7 ( 3.1 )
    -0.9 ( 1.9 )
    -2.9 ( 5.5 )
        Week 25 (n=3,3,3,4,4,5)
    -2.5 ( 3.0 )
    -4.5 ( 1.0 )
    -1.3 ( 2.3 )
    0.3 ( 3.7 )
    -0.8 ( 1.9 )
    -3.1 ( 5.0 )
        Week 27 (n=1,0,0,0,0,0)
    -2.6 ( 99999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
        Week 52 (n=3,2,3,3,3,5)
    -1.8 ( 1.6 )
    -4.1 ( 5.2 )
    -2.0 ( 2.0 )
    0.2 ( 2.7 )
    -1.2 ( 2.0 )
    -3.4 ( 5.4 )
        Week 78 (n=3,2,3,3,3,5)
    -1.9 ( 1.3 )
    -3.5 ( 5.0 )
    -2.9 ( 3.2 )
    -0.9 ( 2.4 )
    -1.5 ( 1.8 )
    -3.5 ( 5.5 )
        Week 104 (n=3,1,3,3,3,5)
    -3.0 ( 2.9 )
    -6.4 ( 99999 )
    -2.8 ( 3.4 )
    0.8 ( 3.8 )
    -1.9 ( 1.5 )
    -3.6 ( 4.1 )
        Week 130 (n=3,1,3,2,3,5)
    -4.0 ( 3.9 )
    -9.8 ( 99999 )
    -2.4 ( 3.3 )
    -1.4 ( 3.9 )
    -1.9 ( 1.6 )
    -3.1 ( 3.9 )
        Week 156 (n=3,1,3,3,3,4)
    -3.6 ( 3.1 )
    -10.4 ( 99999 )
    -1.9 ( 3.2 )
    -1.4 ( 3.2 )
    -2.6 ( 1.8 )
    -4.8 ( 7.9 )
        Week 182 (n=3,1,3,3,2,5)
    -3.5 ( 2.6 )
    -11.6 ( 99999 )
    -2.2 ( 2.7 )
    -3.1 ( 3.2 )
    -1.8 ( 0.4 )
    -3.9 ( 6.5 )
        Week 208 (n=3,1,3,3,3,4)
    -3.2 ( 3.2 )
    -6.5 ( 99999 )
    -2.6 ( 3.9 )
    -3.9 ( 3.5 )
    -1.7 ( 0.6 )
    -5.9 ( 9.5 )
        Week 234 (n=3,1,1,3,3,4)
    -3.4 ( 3.2 )
    -3.8 ( 99999 )
    -4.4 ( 99999 )
    -4.1 ( 2.5 )
    -2.9 ( 1.2 )
    -4.9 ( 7.1 )
        Week 260 (n=2,1,3,2,3,4)
    -1.9 ( 0.4 )
    -10.1 ( 99999 )
    -1.7 ( 4.0 )
    -5.9 ( 0.1 )
    -2.9 ( 1.7 )
    -5.6 ( 8.8 )
        Week 286 (n=1,0,0,2,2,1)
    -7.9 ( 99999 )
    9999 ( 9999 )
    9999 ( 9999 )
    -3.6 ( 2.2 )
    -2.0 ( 0.6 )
    -0.5 ( 99999 )
        Week 312 (n=3,0,2,2,2,2)
    -3.6 ( 3.0 )
    9999 ( 9999 )
    -4.3 ( 3.9 )
    -4.6 ( 1.9 )
    -1.9 ( 0.7 )
    -2.0 ( 0.2 )
        Week 338 (n=0,1,2,1,2,4)
    9999 ( 9999 )
    -0.4 ( 99999 )
    -4.2 ( 5.5 )
    -4.9 ( 99999 )
    -1.8 ( 0.4 )
    -5.7 ( 8.2 )
        Week 364 (n=1,0,0,0,0,0)
    -2.9 ( 99999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
        Week 390 (n=1,0,0,1,0,2)
    -2.6 ( 99999 )
    9999 ( 9999 )
    9999 ( 9999 )
    -1.3 ( 99999 )
    9999 ( 9999 )
    -10.5 ( 11.7 )
        Week 416 (n=0,1,2,2,1,1)
    9999 ( 9999 )
    -12.5 ( 99999 )
    -1.9 ( 3.2 )
    -4.7 ( 2.5 )
    -2.9 ( 99999 )
    -0.7 ( 99999 )
        Week 442 (n=1,0,0,0,1,1)
    -8.5 ( 99999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    -1.9 ( 99999 )
    -0.7 ( 99999 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    TEAEs data was collected from first dose of IMP up to 4 weeks after the last dose of IMP administration (maximum exposure duration: up to 454 weeks). Death data were collected from first dose of IMP up to the end of the study.
    Adverse event reporting additional description
    Analysis was performed on the safety analysis set.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    Group 1: Avalglucosidase alfa 5 mg/kg
    Reporting group description
    		 Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 454 weeks.

    Reporting group title
    Group 1: Avalglucosidase alfa 10 mg/kg
    Reporting group description
    		 Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.

    Reporting group title
    Group 2: Avalglucosidase alfa 20 mg/kg
    Reporting group description
    		 Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 445 weeks.

    Reporting group title
    Group 2: Avalglucosidase alfa 5 mg/kg
    Reporting group description
    		 Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 424 weeks.

    Reporting group title
    Group 2: Avalglucosidase alfa 10 mg/kg
    Reporting group description
    		 Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 450 weeks.

    Reporting group title
    Group 1: Avalglucosidase alfa 20 mg/kg
    Reporting group description
    		 Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 421 weeks.

    Serious adverse events
    		 Group 1: Avalglucosidase alfa 5 mg/kg Group 1: Avalglucosidase alfa 10 mg/kg Group 2: Avalglucosidase alfa 20 mg/kg Group 2: Avalglucosidase alfa 5 mg/kg Group 2: Avalglucosidase alfa 10 mg/kg Group 1: Avalglucosidase alfa 20 mg/kg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 4 (75.00%)
    1 / 3 (33.33%)
    2 / 6 (33.33%)
    1 / 4 (25.00%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    1
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal Cell Carcinoma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Lung Carcinoma Cell Type Unspecified Stage Iv
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Renal Cell Carcinoma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Vascular disorders
    Aortic Aneurysm
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Aortic Dilatation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Arteritis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deep Vein Thrombosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Extravasation Blood
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Peripheral Artery Stenosis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion Spontaneous
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Labour Pain
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    General disorders and administration site conditions
    Chest Discomfort
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chills
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Non-Cardiac Chest Pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute Respiratory Failure
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Respiratory Distress
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Electrocardiogram Q Wave Abnormal
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Injury, poisoning and procedural complications
    Clavicle Fracture
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Fall
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Fractured Sacrum
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Lumbar Vertebral Fracture
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Postimplantation Syndrome
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Subcutaneous Haematoma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Cardiac disorders
    Myocardial Infarction
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Myocardial Ischaemia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Chronic Inflammatory Demyelinating Polyradiculoneuropathy
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Ischaemic Stroke
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastric Ulcer
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Gastrointestinal Haemorrhage
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Rectal Haemorrhage
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Volvulus
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Renal and urinary disorders
    Renal Failure
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cystitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Group 1: Avalglucosidase alfa 5 mg/kg Group 1: Avalglucosidase alfa 10 mg/kg Group 2: Avalglucosidase alfa 20 mg/kg Group 2: Avalglucosidase alfa 5 mg/kg Group 2: Avalglucosidase alfa 10 mg/kg Group 1: Avalglucosidase alfa 20 mg/kg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    4 / 4 (100.00%)
    3 / 3 (100.00%)
    6 / 6 (100.00%)
    4 / 4 (100.00%)
    4 / 4 (100.00%)
    3 / 3 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal Cell Carcinoma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Melanocytic Naevus
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Skin Cancer
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Squamous Cell Carcinoma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    2
    0
    7
    1
    0
    1
    Hot Flush
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Haematoma
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    3
    0
    0
    0
    Flushing
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    1
    0
    0
    0
    Hypotension
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    9
    0
    3
    Pallor
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Pregnancy, puerperium and perinatal conditions
    Afterbirth Pain
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Pregnancy
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 3 (66.67%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    4
    0
    0
    0
    0
    General disorders and administration site conditions
    Application Site Reaction
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Asthenia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    8
    1
    0
    0
    Chest Pain
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    3
    0
    0
    0
    0
    Catheter Site Erythema
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Chest Discomfort
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    Chills
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    Facial Pain
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    1
    2
    0
    0
    Gait Disturbance
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Feeling Hot
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    1
    0
    0
    0
    Fatigue
         subjects affected / exposed
    2 / 4 (50.00%)
    2 / 3 (66.67%)
    3 / 6 (50.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    5
    4
    6
    3
    0
    0
    Infusion Site Extravasation
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Infusion Site Oedema
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Influenza Like Illness
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    4
    0
    0
    0
    Impaired Healing
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Illness
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Infusion Site Pain
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    2
    0
    Infusion Site Rash
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Infusion Site Reaction
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Infusion Site Swelling
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    3
    0
    0
    0
    0
    0
    Injection Site Bruising
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Injection Site Swelling
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Injection Site Haematoma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Malaise
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Non-Cardiac Chest Pain
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
         occurrences all number
    2
    0
    1
    0
    1
    1
    Vaccination Site Reaction
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Pyrexia
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 3 (33.33%)
    3 / 6 (50.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    9
    1
    4
    1
    0
    1
    Peripheral Swelling
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    4
    0
    0
    0
    0
    1
    Pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    2
    3
    0
    1
    Oedema Peripheral
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    1
    0
    1
    Immune system disorders
    Allergy To Arthropod Bite
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Drug Hypersensitivity
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    Seasonal Allergy
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 3 (66.67%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    2
    0
    0
    0
    0
    Hypersensitivity
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Social circumstances
    Pregnancy Of Partner
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    2
    0
    0
    1
    Reproductive system and breast disorders
    Balanoposthitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Pelvic Pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Ovarian Cyst
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Heavy Menstrual Bleeding
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Endometrial Thickening
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    Dysmenorrhoea
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 3 (66.67%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    4
    0
    0
    0
    2
    Respiratory, thoracic and mediastinal disorders
    Acute Respiratory Failure
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Asthma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Allergic Respiratory Symptom
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Choking
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    Chronic Respiratory Failure
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Cough
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    3
    1
    1
    1
    0
    0
    Dyspnoea
         subjects affected / exposed
    3 / 4 (75.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    4
    0
    4
    2
    0
    0
    Epistaxis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    1
    0
    2
    0
    0
    1
    Hyperventilation
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Hypoventilation
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Hypoxia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Increased Upper Airway Secretion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Nasal Congestion
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    3
    0
    0
    3
    0
    0
    Painful Respiration
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Oropharyngeal Pain
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    1 / 4 (25.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    3
    3
    1
    2
    0
    Paranasal Sinus Discomfort
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Pulmonary Mass
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Pulmonary Congestion
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Pleural Effusion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    Respiratory Failure
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Restrictive Pulmonary Disease
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    3
    0
    0
    0
    0
    0
    Sinus Congestion
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Sinus Pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Sleep Apnoea Syndrome
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Tracheal Polyp
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Upper Respiratory Tract Congestion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    Psychiatric disorders
    Panic Attack
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Insomnia
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    7
    0
    2
    0
    0
    0
    Depression
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    Delusional Disorder, Persecutory Type
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Anxiety
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    1
    2
    0
    0
    Product issues
    Device Occlusion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Investigations
    Antimitochondrial Antibody Positive
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Alanine Aminotransferase Increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Antinuclear Antibody Positive
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Blood Chloride Decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Blood Calcium Decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Blood Creatinine Increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    0
    Blood Potassium Decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Blood Lactic Acid Increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Blood Potassium Increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Blood Sodium Decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Blood Pressure Decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Blood Urea Increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Body Temperature Increased
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    Breath Sounds Abnormal
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Electrocardiogram Abnormal
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Haemoglobin Decreased
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Hepatic Enzyme Increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Intraocular Pressure Increased
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Lipoprotein (A) Increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Oxygen Saturation Decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    3 / 6 (50.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    0
    Pulmonary Function Test Decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Streptococcus Test Positive
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Troponin T Increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Troponin Increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Urine Analysis Abnormal
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Weight Decreased
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    1
    3
    0
    0
    Weight Increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Injury, poisoning and procedural complications
    Accidental Overdose
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Adverse Event Following Immunisation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Arthropod Bite
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Avulsion Fracture
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    Bite
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Bone Contusion
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    Chest Injury
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Contusion
         subjects affected / exposed
    3 / 4 (75.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    4
    1
    1
    2
    0
    0
    Electric Shock
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Epicondylitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Fall
         subjects affected / exposed
    3 / 4 (75.00%)
    0 / 3 (0.00%)
    4 / 6 (66.67%)
    4 / 4 (100.00%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
         occurrences all number
    8
    0
    19
    11
    1
    1
    Foot Fracture
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Head Injury
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Infusion Related Reaction
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Iliotibial Band Syndrome
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    4
    0
    0
    0
    0
    0
    Ligament Sprain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Limb Injury
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Muscle Strain
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    2
    0
    0
    0
    Patella Fracture
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Post-Traumatic Pain
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    3
    0
    2
    4
    0
    0
    Procedural Pain
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    Pulmonary Contusion
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Scratch
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Road Traffic Accident
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    Skin Laceration
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Skin Abrasion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Thermal Burn
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Subdural Haematoma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Tooth Fracture
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Traumatic Haematoma
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    3
    0
    4
    0
    0
    0
    Cardiac disorders
    Bradycardia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Conduction Disorder
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Mitral Valve Incompetence
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Mitral Valve Prolapse
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Palpitations
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Myocardial Ischaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Tachycardia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Tachycardia Paroxysmal
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Ventricular Extrasystoles
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Ventricular Arrhythmia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Nervous system disorders
    Cervical Radiculopathy
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Cognitive Disorder
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Dizziness
         subjects affected / exposed
    3 / 4 (75.00%)
    1 / 3 (33.33%)
    2 / 6 (33.33%)
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    12
    1
    4
    6
    0
    0
    Headache
         subjects affected / exposed
    3 / 4 (75.00%)
    2 / 3 (66.67%)
    2 / 6 (33.33%)
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    2 / 3 (66.67%)
         occurrences all number
    15
    12
    22
    16
    0
    8
    Dysaesthesia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Dizziness Postural
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Hyperaesthesia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Hypoaesthesia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Lethargy
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Migraine
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    4
    1
    1
    0
    0
    Migraine With Aura
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Neuralgia
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    3
    0
    0
    0
    1
    0
    Paraesthesia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    4
    0
    3
    0
    0
    0
    Sensory Loss
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Sedation Complication
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Sciatica
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    2
    0
    0
    0
    0
    1
    Sinus Headache
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Somnolence
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Tension Headache
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Syncope
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    1
    1
    0
    0
    Speech Disorder
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Tremor
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    3
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    2
    2
    0
    0
    Iron Deficiency Anaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Leukocytosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Lymphadenopathy
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Lymphopenia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Splenomegaly
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Ear and labyrinth disorders
    Deafness Unilateral
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Ear Pain
         subjects affected / exposed
    3 / 4 (75.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    3
    0
    0
    1
    0
    0
    Ear Discomfort
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Vertigo
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Eye disorders
    Cataract
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    2
    0
    0
    0
    0
    2
    Conjunctival Haemorrhage
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    Dry Eye
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Eye Irritation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Eye Pruritus
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Eyelid Ptosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Lacrimation Increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Swelling Of Eyelid
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Vision Blurred
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    1
    0
    0
    Gastrointestinal disorders
    Abdominal Discomfort
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    2
    0
    0
    Abdominal Distension
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Abdominal Mass
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Abdominal Pain
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    2 / 6 (33.33%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
         occurrences all number
    1
    1
    2
    0
    2
    1
    Abdominal Pain Upper
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 3 (66.67%)
    1 / 6 (16.67%)
    3 / 4 (75.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    5
    1
    3
    0
    0
    Constipation
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    1
    0
    1
    0
    0
    2
    Diarrhoea
         subjects affected / exposed
    4 / 4 (100.00%)
    1 / 3 (33.33%)
    2 / 6 (33.33%)
    2 / 4 (50.00%)
    1 / 4 (25.00%)
    3 / 3 (100.00%)
         occurrences all number
    10
    3
    2
    4
    3
    3
    Dyspepsia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    1
    0
    1
    0
    Diverticulum Intestinal
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Gastrointestinal Pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Dysphagia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    5
    0
    0
    0
    0
    0
    Gastritis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    Gastrooesophageal Reflux Disease
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Haematochezia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Glossodynia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Hiatus Hernia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Irritable Bowel Syndrome
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Lip Haematoma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Lip Swelling
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Malpositioned Teeth
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Melaena
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Peptic Ulcer
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Oral Mucosal Blistering
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Nausea
         subjects affected / exposed
    3 / 4 (75.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    2 / 4 (50.00%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
         occurrences all number
    13
    1
    2
    4
    2
    1
    Toothache
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    Swollen Tongue
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Salivary Hypersecretion
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Vomiting
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    5
    1
    0
    1
    0
    0
    Hepatobiliary disorders
    Hepatitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Hepatic Steatosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Hepatic Fibrosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Skin and subcutaneous tissue disorders
    Actinic Keratosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Dermatitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    Eczema
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Ecchymosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Dermatitis Allergic
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Erythema
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    1
    0
    2
    0
    0
    1
    Hand Dermatitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Hyperhidrosis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    0
    Myxoid Cyst
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Palmar Erythema
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Precancerous Skin Lesion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Pruritus
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    3
    3
    0
    0
    Rash
         subjects affected / exposed
    3 / 4 (75.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    1 / 4 (25.00%)
    2 / 4 (50.00%)
    0 / 3 (0.00%)
         occurrences all number
    9
    1
    1
    1
    2
    0
    Rosacea
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Skin Lesion
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    Skin Striae
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Urticaria
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    0
    Haematuria
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Proteinuria
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Renal Colic
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Urine Flow Decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    Renal Cyst
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 3 (33.33%)
    4 / 6 (66.67%)
    3 / 4 (75.00%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
         occurrences all number
    8
    1
    21
    5
    1
    2
    Back Pain
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 3 (33.33%)
    3 / 6 (50.00%)
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    2 / 3 (66.67%)
         occurrences all number
    2
    2
    10
    2
    0
    2
    Arthritis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Coccydynia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Diffuse Idiopathic Skeletal Hyperostosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Flank Pain
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    Greater Trochanteric Pain Syndrome
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Groin Pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Jaw Clicking
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Intervertebral Disc Degeneration
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Joint Instability
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Muscle Rigidity
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Joint Swelling
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    3 / 4 (75.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    3
    0
    0
    Muscle Spasms
         subjects affected / exposed
    4 / 4 (100.00%)
    1 / 3 (33.33%)
    2 / 6 (33.33%)
    1 / 4 (25.00%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
         occurrences all number
    8
    2
    2
    1
    1
    1
    Muscular Weakness
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    4
    0
    0
    0
    0
    1
    Muscle Tightness
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Musculoskeletal Chest Pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 4 (25.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    1
    1
    0
    Musculoskeletal Stiffness
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Musculoskeletal Pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    4
    0
    0
    2
    Myopathy
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Myalgia
         subjects affected / exposed
    3 / 4 (75.00%)
    1 / 3 (33.33%)
    3 / 6 (50.00%)
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    11
    15
    6
    9
    0
    3
    Neck Pain
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    3 / 6 (50.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    4
    9
    0
    0
    0
    Osteoarthritis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Osteopenia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    Osteochondrosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Osteoporosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    Pain In Extremity
         subjects affected / exposed
    3 / 4 (75.00%)
    1 / 3 (33.33%)
    3 / 6 (50.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    5
    1
    5
    0
    0
    1
    Pain In Jaw
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Rotator Cuff Syndrome
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Tendon Disorder
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Spinal Pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Tendonitis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Torticollis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Infections and infestations
    Acute Sinusitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Bronchitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Covid-19
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    2
    1
    1
    0
    0
    1
    Clostridium Difficile Colitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Diverticulitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    3
    0
    3
    0
    Ear Infection
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    3
    0
    0
    0
    Cystitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Conjunctivitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Gastroenteritis
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    3 / 6 (50.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    3
    3
    1
    0
    0
    Eye Infection
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Fungal Skin Infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Furuncle
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Gastrointestinal Viral Infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Herpes Zoster
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    Gastrointestinal Infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Gastroenteritis Viral
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    1 / 4 (25.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    1
    1
    1
    0
    Oral Herpes
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    14
    3
    0
    0
    0
    0
    Influenza
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    1
    1
    1
    2
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    2 / 4 (50.00%)
    2 / 3 (66.67%)
    2 / 6 (33.33%)
    4 / 4 (100.00%)
    3 / 4 (75.00%)
    2 / 3 (66.67%)
         occurrences all number
    6
    6
    10
    8
    5
    8
    Lower Respiratory Tract Infection
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    Otitis Media
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Pneumonia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Pharyngitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Post Procedural Infection
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Sepsis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Rhinitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    4
    0
    0
    0
    Rectal Abscess
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Sinusitis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    2 / 4 (50.00%)
    2 / 4 (50.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    3
    3
    3
    0
    Tonsillitis
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    2 / 6 (33.33%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 3 (66.67%)
         occurrences all number
    0
    1
    3
    0
    0
    2
    Tooth Abscess
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Tooth Infection
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Viral Tonsillitis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Urinary Tract Infection
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    2
    1
    0
    1
    0
    Upper Respiratory Tract Infection Bacterial
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Viral Upper Respiratory Tract Infection
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Upper Respiratory Tract Infection
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    3 / 6 (50.00%)
    1 / 4 (25.00%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
         occurrences all number
    4
    0
    8
    4
    1
    1
    Metabolism and nutrition disorders
    Gout
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    4
    0
    0
    0
    Dehydration
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Electrolyte Imbalance
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Hypokalaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Iron Deficiency
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Hypovolaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Hyponatraemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    09 Dec 2013
    • Change to the inclusion criteria. • Change to the study duration. • Change to the interim analysis.
    25 Jul 2014
    • Change to the frequency of antibody testing. • Clarification of collection of baseline demographic characteristics. • Addition of time window for study assessments and IMP administration. • Change to the frequency of assessment of body weight. • Clarification of safety assessments. • Clarification of frequency of periodic safety reviews. • Clarification to the handling of IMP. • Clarification of requirement for assessment of vital signs at the end of the post-infusion observation period. • Clarification of immunogenicity assessments. • Clarification of future use of samples. • Clarification of required frequency of pregnancy tests. • Clarification of adverse event of special interest of pregnancy. • Clarification of collection of participant race or ethnicity. • Clarification of follow-up period. • Clarification of obligations of the Sponsor. • Clarification of coordinating Investigator.
    29 Jan 2016
    • 20 mg/kg body weight qow was selected as the final avalglucosidase alfa dose for the extension study. • Change to the visit schedule for participants switching from 5 mg/kg qow or 10 mg/kg qow to 20 mg/kg qow.
    27 Nov 2017
    • Added option of home infusion of IMP for participants meeting all eligibility requirements in regions where home infusion is deemed appropriate.
    06 Sep 2019
    • To comply with the Data Monitoring Committee recommendation with regards to home infusions. • To reference the Investigator’s Brochure in the protocol. • To extend the additional follow-up period until avalglucosidase alfa was approved in the participant’s country. • To comply with the United Kingdom position regarding the protocol language with regards to the study follow-up period duration.
    21 Dec 2020
    • To include the recommendations that were developed for the Coronavirus Disease 2019 pandemic period and were shared with the sites/Investigators. These recommendations were remained applicable after the end of the pandemic, especially the information regarding the post-infusion surveillance period. • To revise the text in Sections 12 (regulatory, ethical, and study oversight considerations), 13 (study monitoring), and 14 (additional requirements) as per the current Sanofi protocol template to use the updated wordings that are compliant with general guidance, including monitoring techniques. • To update Section 8.1 (investigational medicinal products) for details regarding home infusions to harmonize this text across the different studies included in the avalglucosidase alfa development program.

    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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