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    Clinical Trial Results:
    An open-label multi-part first-in-human study of oral LMI070 in infants with Type 1 spinal muscular atrophy.

    Summary
    EudraCT number
    2014-002053-19
    Trial protocol
    DK   IT   DE   BE   NL   CZ   PL   HU   BG  
    Global end of trial date
    29 Dec 2022

    Results information
    Results version number
    v2(current)
    This version publication date
    20 Jun 2025
    First version publication date
    14 Jul 2023
    Other versions
    v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    CLMI070X2201
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02268552
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    Novartis Campus, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    29 Dec 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Dec 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Part 1: Determine the safety and tolerability of ascending weekly doses and estimate the maximum tolerated dose (MTD) of branaplam in infants with Type 1 SMA. Part 2: Evaluate the safety and tolerability of 2 doses of branaplam administered weekly for 52 weeks in subjects with Type 1 SMA. Part 3: Assess long term safety and tolerability of extended, once a week branaplam treatment in subjects with Type 1 SMA who have had at least 52 weeks of treatment in either Part 1 or 2 of this protocol.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    02 Apr 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Belgium: 5
    Country: Number of subjects enrolled
    Bulgaria: 1
    Country: Number of subjects enrolled
    Denmark: 3
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    Italy: 2
    Country: Number of subjects enrolled
    Poland: 9
    Country: Number of subjects enrolled
    Russian Federation: 17
    Worldwide total number of subjects
    38
    EEA total number of subjects
    21
    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)
    38
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Cohorts in Part 1 were enrolled sequentially following a 14 day dose-limiting toxicity (DLT) window for each cohort before escalating to the next level. Forty participants were enrolled but only 38 received treatment.

    Period 1
    Period 1 title
    Part 1 & Part 2
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Part 1 LMI070 6mg/m2
    Arm description
    Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes
    Arm type
    Experimental

    Investigational medicinal product name
    branaplam
    Investigational medicinal product code
    LMI070
    Other name
    Pharmaceutical forms
    Gastroenteral solution, Oral solution
    Routes of administration
    Enteral use , Oral use
    Dosage and administration details
    Branaplam in a dose strength of 6mg/m2 administered by the enteral route or orally depending ability to swallow

    Arm title
    Part 1 LMI070 12mg/m2
    Arm description
    Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes
    Arm type
    Experimental

    Investigational medicinal product name
    branaplam
    Investigational medicinal product code
    LMI070
    Other name
    Pharmaceutical forms
    Gastroenteral solution, Oral solution
    Routes of administration
    Enteral use , Oral use
    Dosage and administration details
    Branaplam in a dose strength of 12mg/m2 administered by the enteral route or orally depending ability to swallow

    Arm title
    Part 1 LMI070 24mg/m2
    Arm description
    Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes
    Arm type
    Experimental

    Investigational medicinal product name
    branaplam
    Investigational medicinal product code
    LMI070
    Other name
    Pharmaceutical forms
    Gastroenteral solution, Oral solution
    Routes of administration
    Enteral use , Oral use
    Dosage and administration details
    Branaplam in a dose strength of 24mg/m2 administered by the enteral route or orally depending ability to swallow

    Arm title
    Part 1 LMI070 48mg/m2
    Arm description
    Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes
    Arm type
    Experimental

    Investigational medicinal product name
    branaplam
    Investigational medicinal product code
    LMI070
    Other name
    Pharmaceutical forms
    Gastroenteral solution, Oral solution
    Routes of administration
    Enteral use , Oral use
    Dosage and administration details
    Branaplam in a dose strength of 48mg/m2 administered by the enteral route or orally depending ability to swallow

    Arm title
    Part 1 LMI070 60mg/m2
    Arm description
    Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes
    Arm type
    Experimental

    Investigational medicinal product name
    branaplam
    Investigational medicinal product code
    LMI070
    Other name
    Pharmaceutical forms
    Gastroenteral solution, Oral solution
    Routes of administration
    Enteral use , Oral use
    Dosage and administration details
    Branaplam in a dose strength of 60mg/m2 administered by the enteral route or orally depending ability to swallow

    Arm title
    Part 2 LMI070 0.625 mg/kg
    Arm description
    LMI070 0.625 mg/kg by enteral route via feeding tube or oral
    Arm type
    Experimental

    Investigational medicinal product name
    branaplam
    Investigational medicinal product code
    LMI070
    Other name
    Pharmaceutical forms
    Gastroenteral solution, Oral solution
    Routes of administration
    Enteral use , Oral use
    Dosage and administration details
    Branaplam in a dose strength of 0.625 mg/kg administered by the enteral route or orally depending ability to swallow

    Arm title
    Part 2 LMI070 2.5 mg/kg
    Arm description
    LMI070 2.5 mg/kg by enteral route via feeding tube or oral
    Arm type
    Experimental

    Investigational medicinal product name
    branaplam
    Investigational medicinal product code
    LMI070
    Other name
    Pharmaceutical forms
    Gastroenteral solution, Oral solution
    Routes of administration
    Enteral use , Oral use
    Dosage and administration details
    Branaplam in a dose strength of 2.5 mg/kg administered by the enteral route or orally depending ability to swallow

    Number of subjects in period 1
    Part 1 LMI070 6mg/m2 Part 1 LMI070 12mg/m2 Part 1 LMI070 24mg/m2 Part 1 LMI070 48mg/m2 Part 1 LMI070 60mg/m2 Part 2 LMI070 0.625 mg/kg Part 2 LMI070 2.5 mg/kg
    Started
    2
    2
    2
    4
    3
    10
    15
    Completed
    1
    1
    1
    1
    3
    10
    12
    Not completed
    1
    1
    1
    3
    0
    0
    3
         Death
    1
    1
    1
    2
    -
    -
    2
         Subject/guardian decision
    -
    -
    -
    1
    -
    -
    1
    Period 2
    Period 2 title
    Part 3 Extension
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    No

    Arm title
    Part 1 LMI070 6mg/m2
    Arm description
    Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes
    Arm type
    Experimental

    Investigational medicinal product name
    branaplam
    Investigational medicinal product code
    LMI070
    Other name
    Pharmaceutical forms
    Gastroenteral solution, Oral solution
    Routes of administration
    Enteral use , Oral use
    Dosage and administration details
    Branaplam in a starting dose of 6mg/m2 administered by the enteral route or orally depending ability to swallow

    Arm title
    Part 1 LMI070 12mg/m2
    Arm description
    Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes
    Arm type
    Experimental

    Investigational medicinal product name
    branaplam
    Investigational medicinal product code
    LMI070
    Other name
    Pharmaceutical forms
    Gastroenteral solution, Oral solution
    Routes of administration
    Enteral use , Oral use
    Dosage and administration details
    Branaplam in a starting dose of 12mg/m2 administered by the enteral route or orally depending ability to swallow

    Arm title
    Part 1 LMI070 24mg/m2
    Arm description
    Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes
    Arm type
    Experimental

    Investigational medicinal product name
    branaplam
    Investigational medicinal product code
    LMI070
    Other name
    Pharmaceutical forms
    Gastroenteral solution, Oral solution
    Routes of administration
    Enteral use , Oral use
    Dosage and administration details
    Branaplam in a starting dose of 24mg/m2 administered by the enteral route or orally depending ability to swallow

    Arm title
    Part 1 LMI070 48mg/m2
    Arm description
    Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes
    Arm type
    Experimental

    Investigational medicinal product name
    branaplam
    Investigational medicinal product code
    LMI070
    Other name
    Pharmaceutical forms
    Gastroenteral solution, Oral solution
    Routes of administration
    Enteral use , Oral use
    Dosage and administration details
    Branaplam in a starting dose of 48mg/m2 administered by the enteral route or orally depending ability to swallow

    Arm title
    Part 1 LMI070 60mg/m2
    Arm description
    Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes
    Arm type
    Experimental

    Investigational medicinal product name
    branaplam
    Investigational medicinal product code
    LMI070
    Other name
    Pharmaceutical forms
    Gastroenteral solution, Oral solution
    Routes of administration
    Enteral use , Oral use
    Dosage and administration details
    Branaplam in a starting dose of 60mg/m2 administered by the enteral route or orally depending ability to swallow

    Arm title
    Part 2 LMI070 0.625 mg/kg
    Arm description
    LMI070 0.625 mg/kg by enteral route via feeding tube or oral
    Arm type
    Experimental

    Investigational medicinal product name
    branaplam
    Investigational medicinal product code
    LMI070
    Other name
    Pharmaceutical forms
    Gastroenteral solution, Oral solution
    Routes of administration
    Enteral use , Oral use
    Dosage and administration details
    Branaplam in a starting dose of 0.625 mg/kg administered by the enteral route or orally depending ability to swallow

    Arm title
    Part 2 LMI070 2.5 mg/kg
    Arm description
    LMI070 2.5 mg/kg by enteral route via feeding tube or oral
    Arm type
    Experimental

    Investigational medicinal product name
    branaplam
    Investigational medicinal product code
    LMI070
    Other name
    Pharmaceutical forms
    Gastroenteral solution, Oral solution
    Routes of administration
    Enteral use , Oral use
    Dosage and administration details
    Branaplam in a starting dose of 2.5 mg/kg administered by the enteral route or orally depending ability to swallow

    Number of subjects in period 2
    Part 1 LMI070 6mg/m2 Part 1 LMI070 12mg/m2 Part 1 LMI070 24mg/m2 Part 1 LMI070 48mg/m2 Part 1 LMI070 60mg/m2 Part 2 LMI070 0.625 mg/kg Part 2 LMI070 2.5 mg/kg
    Started
    1
    1
    1
    1
    3
    10
    12
    Completed
    0
    0
    0
    0
    0
    0
    0
    Not completed
    1
    1
    1
    1
    3
    10
    12
         Adverse event, serious fatal
    -
    1
    1
    1
    1
    1
    -
         Early termination of trial
    1
    -
    -
    -
    2
    9
    11
         Subject/guardian decision
    -
    -
    -
    -
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Part 1 LMI070 6mg/m2
    Reporting group description
    Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes

    Reporting group title
    Part 1 LMI070 12mg/m2
    Reporting group description
    Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes

    Reporting group title
    Part 1 LMI070 24mg/m2
    Reporting group description
    Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes

    Reporting group title
    Part 1 LMI070 48mg/m2
    Reporting group description
    Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes

    Reporting group title
    Part 1 LMI070 60mg/m2
    Reporting group description
    Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes

    Reporting group title
    Part 2 LMI070 0.625 mg/kg
    Reporting group description
    LMI070 0.625 mg/kg by enteral route via feeding tube or oral

    Reporting group title
    Part 2 LMI070 2.5 mg/kg
    Reporting group description
    LMI070 2.5 mg/kg by enteral route via feeding tube or oral

    Reporting group values
    Part 1 LMI070 6mg/m2 Part 1 LMI070 12mg/m2 Part 1 LMI070 24mg/m2 Part 1 LMI070 48mg/m2 Part 1 LMI070 60mg/m2 Part 2 LMI070 0.625 mg/kg Part 2 LMI070 2.5 mg/kg Total
    Number of subjects
    2 2 2 4 3 10 15 38
    Age categorical
    Units: Subjects
        Infants and toddlers (28 days-23 months)
    2 2 2 4 3 10 15 38
        In utero
    0 0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0 0 0 0 0 0
        Newborns (0-27 days)
    0 0 0 0 0 0 0 0
        Children (2-11 years)
    0 0 0 0 0 0 0 0
        Adolescents (12-17 years)
    0 0 0 0 0 0 0 0
        Adults (18-64 years)
    0 0 0 0 0 0 0 0
        From 65-84 years
    0 0 0 0 0 0 0 0
        85 years and over
    0 0 0 0 0 0 0 0
    Age Continuous
    Units: months
        arithmetic mean (standard deviation)
    3.0 ( 1.41 ) 4.5 ( 0.71 ) 3.5 ( 2.12 ) 3.8 ( 1.71 ) 5.3 ( 2.08 ) 4.38 ( 1.521 ) 3.81 ( 1.188 ) -
    Sex: Female, Male
    Units: participants
        Female
    1 0 2 3 2 5 9 22
        Male
    1 2 0 1 1 5 6 16
    Race/Ethnicity, Customized
    Units: Subjects
        Caucasian
    2 2 1 3 2 10 14 34
        Asian
    0 0 0 0 0 0 1 1
        Other
    0 0 1 1 0 0 0 2
        Black
    0 0 0 0 1 0 0 1

    End points

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    End points reporting groups
    Reporting group title
    Part 1 LMI070 6mg/m2
    Reporting group description
    Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes

    Reporting group title
    Part 1 LMI070 12mg/m2
    Reporting group description
    Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes

    Reporting group title
    Part 1 LMI070 24mg/m2
    Reporting group description
    Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes

    Reporting group title
    Part 1 LMI070 48mg/m2
    Reporting group description
    Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes

    Reporting group title
    Part 1 LMI070 60mg/m2
    Reporting group description
    Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes

    Reporting group title
    Part 2 LMI070 0.625 mg/kg
    Reporting group description
    LMI070 0.625 mg/kg by enteral route via feeding tube or oral

    Reporting group title
    Part 2 LMI070 2.5 mg/kg
    Reporting group description
    LMI070 2.5 mg/kg by enteral route via feeding tube or oral
    Reporting group title
    Part 1 LMI070 6mg/m2
    Reporting group description
    Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes

    Reporting group title
    Part 1 LMI070 12mg/m2
    Reporting group description
    Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes

    Reporting group title
    Part 1 LMI070 24mg/m2
    Reporting group description
    Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes

    Reporting group title
    Part 1 LMI070 48mg/m2
    Reporting group description
    Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes

    Reporting group title
    Part 1 LMI070 60mg/m2
    Reporting group description
    Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes

    Reporting group title
    Part 2 LMI070 0.625 mg/kg
    Reporting group description
    LMI070 0.625 mg/kg by enteral route via feeding tube or oral

    Reporting group title
    Part 2 LMI070 2.5 mg/kg
    Reporting group description
    LMI070 2.5 mg/kg by enteral route via feeding tube or oral

    Subject analysis set title
    Part 1 LMI070 Overall
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Enteral route via feeding tube or oral. There were 5 cohorts 0.3125, 0.625, 1.25, 2.5, 3.125 mg/kg weekly doses for 2 weeks

    Subject analysis set title
    Parts 1 & 3 Overall
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants who completed 52 weeks of treatment in Part 1 could have continued on same dose or moved to optimal dose (2.5 mg/kg) in Part 3.

    Subject analysis set title
    Parts 2 & 3 Overall
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants who completed 52 weeks of treatment in Part 2 could have continued on same dose or moved to optimal dose (2.5 mg/kg) in Part 3.

    Primary: Number of participants with treatment emergent adverse events (TEAEs), serious adverse events and deaths- SAS

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    End point title
    Number of participants with treatment emergent adverse events (TEAEs), serious adverse events and deaths- SAS [1]
    End point description
    TEAEs are defined as adverse events starting on or after the first dose of study treatment that were absent pre-treatment, or events present prior to the first dose but increased in severity after the first dose. Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post last treatment.
    End point type
    Primary
    End point timeframe
    Baseline up to approximately 83 months
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis were planned for primary endpoints on this study
    End point values
    Part 1 LMI070 6mg/m2 Part 1 LMI070 12mg/m2 Part 1 LMI070 24mg/m2 Part 1 LMI070 48mg/m2 Part 1 LMI070 60mg/m2 Part 2 LMI070 0.625 mg/kg Part 2 LMI070 2.5 mg/kg
    Number of subjects analysed
    2
    2
    2
    4
    3
    10
    15
    Units: participants
        Participants with adverse events
    2
    2
    2
    4
    3
    10
    15
        Participants with serious adverse events
    2
    2
    2
    4
    3
    8
    11
        Deaths
    1
    2
    2
    3
    1
    1
    2
    No statistical analyses for this end point

    Primary: Number of participants with dose limiting toxicities (DLT) in Part 1 - Safety analysis set (SAS)

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    End point title
    Number of participants with dose limiting toxicities (DLT) in Part 1 - Safety analysis set (SAS) [2] [3]
    End point description
    A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant therapies that occurs within the first 14 days of treatment with LMI070 and meets any of the criteria for blood and lymphatic system disorders, gastrointestinal disorders, investigations and other toxicities considered clinically significant.
    End point type
    Primary
    End point timeframe
    Baseline up to 2 weeks for Part 1
    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: No statistical analysis were planned for primary endpoints on this study
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: DLTs were only evaluated in part 1 participants
    End point values
    Part 1 LMI070 6mg/m2 Part 1 LMI070 12mg/m2 Part 1 LMI070 24mg/m2 Part 1 LMI070 48mg/m2 Part 1 LMI070 60mg/m2
    Number of subjects analysed
    2
    2
    2
    4
    3
    Units: Participants
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Summary of plasma pharmacokinetic (PK) parameter area under the curve (AUCinf) after a single dose - Part 1 - Pharmacokinetics analysis set (PAS)

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    End point title
    Summary of plasma pharmacokinetic (PK) parameter area under the curve (AUCinf) after a single dose - Part 1 - Pharmacokinetics analysis set (PAS)
    End point description
    The area under the plasma (or serum or blood) concentration-time curve from time zero to infinity [mass x time / volume]. Due to EudraCT system limitations, data fields in the table cannot contain letters (eg. NA indicating ‘not applicable’). Therefore, not applicable values are indicated as ‘999’.
    End point type
    Secondary
    End point timeframe
    from 0 h to 168 h after first/single dose
    End point values
    Part 1 LMI070 Overall
    Number of subjects analysed
    12
    Units: h*ng/mL
    arithmetic mean (standard deviation)
        0.321 mg/kg - Actual n=2
    378 ( 31.9 )
        0.654 mg/kg - Actual n=2
    892 ( 12.3 )
        1.39 mg/kg - Actual n=1
    1820 ( 999 )
        2.49 mg/kg - Actual n=4
    3310 ( 1340 )
        2.94 mg/kg - Actual n=3
    3800 ( 1590 )
    No statistical analyses for this end point

    Secondary: Summary of plasma pharmacokinetic (PK) parameter area under the curve (AUCinf) for all observation periods - Part 1 - PAS

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    End point title
    Summary of plasma pharmacokinetic (PK) parameter area under the curve (AUCinf) for all observation periods - Part 1 - PAS
    End point description
    The area under the plasma (or serum or blood) concentration-time curve from time zero to infinity [mass x time / volume] for all observations. AUC values used for comparison are combined from AUCinf values after single dose and AUC 0-168h values after repeated administration.
    End point type
    Secondary
    End point timeframe
    from 0 h to 168 h after first/single dose
    End point values
    Part 1 LMI070 Overall
    Number of subjects analysed
    13 [4]
    Units: h*ng/mL
    arithmetic mean (standard deviation)
        0.299 mg/kg - Actual
    413 ( 98.3 )
        0.644 mg/kg - Actual
    761 ( 170 )
        1.30 mg/kg - Actual
    1340 ( 381 )
        2.52 mg/kg - Actual
    3310 ( 850 )
        2.95 mg/kg - Actual
    4210 ( 1030 )
    Notes
    [4] - Total number of observations 63
    No statistical analyses for this end point

    Secondary: Summary of plasma pharmacokinetic (PK) parameter Cmax after a single dose - Part 1 - PAS

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    End point title
    Summary of plasma pharmacokinetic (PK) parameter Cmax after a single dose - Part 1 - PAS
    End point description
    The observed maximum plasma concentration following drug administration [mass / volume). Due to EudraCT system limitations, data fields in the table cannot contain letters (eg. NA indicating ‘not applicable’). Therefore, not applicable values are indicated as ‘999’.
    End point type
    Secondary
    End point timeframe
    from 0 h to 168 h after first/single dose
    End point values
    Part 1 LMI070 Overall
    Number of subjects analysed
    12
    Units: ng/mL
    arithmetic mean (standard deviation)
        0.321 mg/kg - Actual n=2
    9.10 ( 1.22 )
        0.654 mg/kg - Actual n=2
    18.6 ( 1.63 )
        1.39 mg/kg - Actual n=1
    55.6 ( 999 )
        2.49 mg/kg - Actual n=4
    53.2 ( 9.50 )
        2.94 mg/kg - Actual n=3
    72.4 ( 16.7 )
    No statistical analyses for this end point

    Secondary: Summary of plasma pharmacokinetic (PK) parameter Cmax for all observation periods - Part 1 - PAS

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    End point title
    Summary of plasma pharmacokinetic (PK) parameter Cmax for all observation periods - Part 1 - PAS
    End point description
    The observed maximum plasma (or serum or blood) concentration following drug administration [mass / volume
    End point type
    Secondary
    End point timeframe
    from 0 h to 168 h after first/single dose
    End point values
    Part 1 LMI070 Overall
    Number of subjects analysed
    13 [5]
    Units: ng/mL
    arithmetic mean (standard deviation)
        0.299 mg/kg - Actual
    8.84 ( 3.58 )
        0.644 mg/kg - Actual
    15.3 ( 4.10 )
        1.30 mg/kg - Actual
    37.8 ( 12.8 )
        2.51 mg/kg - Actual
    69.1 ( 15.7 )
        2.95 mg/kg - Actual
    96.5 ( 32.7 )
    Notes
    [5] - Total number of observations 89
    No statistical analyses for this end point

    Secondary: Summary of plasma pharmacokinetic (PK) parameter area under the curve (AUC) after a single dose - Part 2 - PAS

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    End point title
    Summary of plasma pharmacokinetic (PK) parameter area under the curve (AUC) after a single dose - Part 2 - PAS [6]
    End point description
    The area under the plasma (or serum or blood) concentration-time curve from time zero to infinity [mass x time / volume)
    End point type
    Secondary
    End point timeframe
    from 0 h to 168 h after first/single dose
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK parameters for part 1 and 2 are reported separately
    End point values
    Part 2 LMI070 0.625 mg/kg Part 2 LMI070 2.5 mg/kg
    Number of subjects analysed
    10
    15
    Units: h*ng/mL
        arithmetic mean (standard deviation)
    1150 ( 357 )
    4060 ( 734 )
    No statistical analyses for this end point

    Secondary: Summary of plasma pharmacokinetic (PK) parameter area under the curve (AUC) for all observation periods - Part 2 - PAS

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    End point title
    Summary of plasma pharmacokinetic (PK) parameter area under the curve (AUC) for all observation periods - Part 2 - PAS [7]
    End point description
    The area under the plasma (or serum or blood) concentration-time curve from time zero to infinity [mass x time / volume). AUC values used for comparison are combined from AUCinf values after single dose and AUC0-168h values after repeated administration.
    End point type
    Secondary
    End point timeframe
    from 0 h to 168 h after first/single dose
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK parameters for part 1 and 2 are reported separately
    End point values
    Part 2 LMI070 0.625 mg/kg Part 2 LMI070 2.5 mg/kg
    Number of subjects analysed
    10 [8]
    15 [9]
    Units: h*ng/mL
        arithmetic mean (standard deviation)
    1020 ( 278 )
    3470 ( 909 )
    Notes
    [8] - Number of observations 28
    [9] - Number of observations 28
    No statistical analyses for this end point

    Secondary: Summary of plasma pharmacokinetic (PK) parameter Cmax for all observation periods - Part 2 - PAS

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    End point title
    Summary of plasma pharmacokinetic (PK) parameter Cmax for all observation periods - Part 2 - PAS [10]
    End point description
    The observed maximum plasma (or serum or blood) concentration following drug administration [mass / volume)
    End point type
    Secondary
    End point timeframe
    from 0 h to 168 h after first/single dose
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK parameters for part 1 and 2 are reported separately
    End point values
    Part 2 LMI070 0.625 mg/kg Part 2 LMI070 2.5 mg/kg
    Number of subjects analysed
    10 [11]
    15 [12]
    Units: ng/mL
        arithmetic mean (standard deviation)
    21.7 ( 5.71 )
    77.4 ( 27.5 )
    Notes
    [11] - Number of observations 29
    [12] - Number of observations 38
    No statistical analyses for this end point

    Secondary: Summary of plasma pharmacokinetic (PK) parameter Cmax for a single dose - Part 2 - PAS

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    End point title
    Summary of plasma pharmacokinetic (PK) parameter Cmax for a single dose - Part 2 - PAS [13]
    End point description
    The observed maximum plasma (or serum or blood) concentration following drug administration [mass / volume)
    End point type
    Secondary
    End point timeframe
    from 0 h to 168 h after first/single dose
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK parameters for part 1 and 2 are reported separately
    End point values
    Part 2 LMI070 0.625 mg/kg Part 2 LMI070 2.5 mg/kg
    Number of subjects analysed
    10
    15
    Units: ng/mL
        arithmetic mean (standard deviation)
    22.0 ( 5.70 )
    82.0 ( 22.5 )
    No statistical analyses for this end point

    Secondary: Change from baseline in growth parameters: chest circumference, head circumference and body length - Full analysis set (FAS)

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    End point title
    Change from baseline in growth parameters: chest circumference, head circumference and body length - Full analysis set (FAS)
    End point description
    The effect of branaplam on growth parameters: Length (measured from the top of the head to the sole of the foot), Head circumference and Chest circumference (measured across nipple line). Mean change from baseline in cm is presented In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52 and Month 6 of Part 3
    End point values
    Parts 1 & 3 Overall Parts 2 & 3 Overall
    Number of subjects analysed
    13
    25
    Units: cm
    arithmetic mean (standard deviation)
        Chest - Week 52 n=10,18
    4.68 ( 2.4769 )
    5.656 ( 3.0167 )
        Chest - P3 Month 6 n=6,17
    14.750 ( 0548 )
    8.582 ( 2.7423 )
        Head -Week 52 n=10,18
    5.030 ( 1.1235 )
    5.111 ( 1.3407 )
        Head -P3 Month 6 n=6,17
    9.717 ( 1.8766 )
    6.359 ( 1.2971 )
        Length - Week 52 n=10,19
    16.950 ( 3.7825 )
    16.942 ( 4.5806 )
        Length - P3 Month 6 n=5,18
    52.140 ( 9.8766 )
    22.944 ( 3.7686 )
    No statistical analyses for this end point

    Secondary: Change from baseline in respiratory function: Pulse oximetry - FAS

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    End point title
    Change from baseline in respiratory function: Pulse oximetry - FAS
    End point description
    The effect of branaplam on pulse oximetry in percentage of oxygen saturation was evaluated using a probe that measures oxygen in the blood. Mean change from baseline in percentage of oxygen saturation is reported. Negative numbers indicate a decrease from baseline In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52 and Month 6 of Part 3
    End point values
    Parts 1 & 3 Overall Parts 2 & 3 Overall
    Number of subjects analysed
    13
    25
    Units: percentage
    arithmetic mean (standard deviation)
        Week 52 n=9,19
    -0.8 ( 2.59 )
    -0.1 ( 1.56 )
        P3 Month 6 n=6,19
    -0.7 ( 2.58 )
    0.0 ( 1.83 )
    No statistical analyses for this end point

    Secondary: Change from baseline in growth parameter: body weight - FAS

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    End point title
    Change from baseline in growth parameter: body weight - FAS
    End point description
    The effect of Branaplam on body weight in Kg was measured using a weight scale. Mean change from baseline in Kg is presented In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52 and Month 6 of Part 3
    End point values
    Parts 1 & 3 Overall Parts 2 & 3 Overall
    Number of subjects analysed
    13
    25
    Units: kg
    arithmetic mean (standard deviation)
        Week 52 n=10,19
    2.739 ( 1.3545 )
    3.145 ( 1.5089 )
        P3 Month 6 n=6,19
    9.546 ( 3.5069 )
    4.402 ( 1.3250 )
    No statistical analyses for this end point

    Secondary: Number of participants with presence of paradoxical breathing - FAS

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    End point title
    Number of participants with presence of paradoxical breathing - FAS
    End point description
    A paradoxical breathing occurs when one compartment moves out of phase compared to another one. In SMA type I, paradoxical breathing is often a sign of breathing problems where the pulmonary ribcage moves inward during inspiration rather than outward while the abdomen expands. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52 and Month 6 of Part 3
    End point values
    Parts 1 & 3 Overall Parts 2 & 3 Overall
    Number of subjects analysed
    13
    25
    Units: participants
        Week 52 n=9,19
    5
    15
        P3 Month 6 n=6,18
    4
    14
    No statistical analyses for this end point

    Secondary: Change from baseline in respiratory function: Respiratory rate - FAS

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    End point title
    Change from baseline in respiratory function: Respiratory rate - FAS
    End point description
    The effect of branaplam on respiratory rate was evaluated by counting the number of breaths for one minute. Mean change from baseline in breaths per minute is reported” In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52 and Month 6 of Part 3
    End point values
    Parts 1 & 3 Overall Parts 2 & 3 Overall
    Number of subjects analysed
    12
    25
    Units: breaths per minute
    arithmetic mean (standard deviation)
        Week 52 n=8,19
    41.3 ( 7.57 )
    40.5 ( 13.46 )
        P3 Month 6 n=6,18
    29.2 ( 6.59 )
    37.2 ( 8.95 )
    No statistical analyses for this end point

    Secondary: Change from baseline in respiratory function: Chest circumference during quiet breathing - end of inspiration and expiration - FAS

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    End point title
    Change from baseline in respiratory function: Chest circumference during quiet breathing - end of inspiration and expiration - FAS
    End point description
    The effect of branaplam on respiratory status was evaluated by measuring the circumference of the ribcage while taking a breathe in and out while quiet or sleeping. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52 and Month 6 of Part 3
    End point values
    Parts 1 & 3 Overall Parts 2 & 3 Overall
    Number of subjects analysed
    0 [14]
    18
    Units: cm
    arithmetic mean (standard deviation)
        Week 52 - end of inspiration n=0,18
    ( )
    5.964 ( 3.6345 )
        P3 Month 6 - end of inspiration n=0,17
    ( )
    8.535 ( 3.3083 )
        Week 52 - end of expiration n=0,18
    ( )
    6.033 ( 3.9466 )
        P3 Month 6 - end of expiration n=0,18
    ( )
    9.147 ( 3.5755 )
    Notes
    [14] - no participants with an available measure for this endpoint
    No statistical analyses for this end point

    Secondary: Summary of CHOP INTEND total score - Parts 1 and 3 and Parts 2 and 3 - FAS

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    End point title
    Summary of CHOP INTEND total score - Parts 1 and 3 and Parts 2 and 3 - FAS
    End point description
    CHOP INTEND is a motor test measure for SMA Type 1 and similarly weak infants with neuromuscular disease. The CHOP INTEND provides a useful measure of motor skills and strength in this population. It is a 16 item, 64 point scale. Each item (motor skill) is given a score from zero to 4: zero indicates can't complete the movement, 1 to 3 indicates partial performance and a 4 indicates person can complete the movement on their own without assistance. These scores are added up to a possible total score of 64 and higher scores indicate better outcomes. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 & Part 2&3) irrespective of study dose or route of administration. Due to EudraCT system limitations, data fields in the table cannot contain letters (eg. NA ‘not applicable’). Therefore, not applicable values are indicated as ‘999’.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52 and Month 6 of Part 3
    End point values
    Parts 1 & 3 Overall Parts 2 & 3 Overall
    Number of subjects analysed
    8
    18
    Units: scores on a scale
    arithmetic mean (standard deviation)
        Week 52 n=8,18
    38.1 ( 8.69 )
    43.6 ( 6.79 )
        Part 3, Month 6 n=1,14
    26.0 ( 999 )
    44.7 ( 8.73 )
    No statistical analyses for this end point

    Secondary: Number of participants fed orally or by feeding tube for Parts 1 and 3 and Parts 2 and 3 - FAS

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    End point title
    Number of participants fed orally or by feeding tube for Parts 1 and 3 and Parts 2 and 3 - FAS
    End point description
    To evaluate the efficacy of branaplam on preservation of oral feeding In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration.
    End point type
    Secondary
    End point timeframe
    Baseline up Week 78
    End point values
    Parts 1 & 3 Overall Parts 2 & 3 Overall
    Number of subjects analysed
    13
    25
    Units: participants
        Only exclusively orally fed
    3
    18
        Only exclusively tube fed
    0
    0
        Started on orally fed, switched to tube fed
    0
    2
        Started on tube fed, switched to orally fed
    0
    0
        Other (mixture of both tube and oral feeding)
    8
    5
    No statistical analyses for this end point

    Secondary: Number of participants and HINE Motor subscale milestones (ability to sit, stand or walk without support) - FAS

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    End point title
    Number of participants and HINE Motor subscale milestones (ability to sit, stand or walk without support) - FAS
    End point description
    HINE Section 2 is a standardized evaluation of motor function. It evaluates 8 items; grasp, head control, kicking, rolling over, sitting up, crawling, standing and walking. Motor skills are assigned a score of 0 to 3 to 5 points and zero means the child lacks that motor skill. The maximum score is 26 which is dependent on age, level of development and severity of disease. A higher score is a better outcome. This assessment was added with amendment 6, therefore no baseline was available. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration.
    End point type
    Secondary
    End point timeframe
    Week 52 and Month 6 of Part 3
    End point values
    Parts 1 & 3 Overall Parts 2 & 3 Overall
    Number of subjects analysed
    13
    25
    Units: participants
        Week 52 Sitting - Stable independent n=3,22
    1
    1
        Week 52 Standing - Supports weight n=2,22
    0
    2
        Week 52: Walking - Makes any attempt n=2,16
    0
    1
        Pt 3, Month 6: Sitting - Stable independent n=5,15
    0
    4
        Pt 3, Month 6: Standing - Supports weight n=4,15
    0
    5
        Pt 3, Month 6: Walking - Makes any attempt n=4,11
    0
    2
    No statistical analyses for this end point

    Secondary: Summary of Hammersmith Infant Neurologic Examination Section 2 (HINE-2) - FAS

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    End point title
    Summary of Hammersmith Infant Neurologic Examination Section 2 (HINE-2) - FAS
    End point description
    HINE Section 2 is a standardized evaluation of motor function. It evaluates 8 items; grasp, head control, kicking, rolling over, sitting up, crawling, standing and walking. Motor skills are assigned a score of 0 to 3 to 5 points and zero means the child lacks that motor skill. The maximum score is 26 which is dependent on age, level of development and severity of disease. A higher score is a better outcome. This assessment was added with amendment 6, therefore no baseline was available. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration.
    End point type
    Secondary
    End point timeframe
    Week 52 and Month 6 of Part 3
    End point values
    Parts 1 & 3 Overall Parts 2 & 3 Overall
    Number of subjects analysed
    5
    25
    Units: total scores
    arithmetic mean (standard deviation)
        Week 52 n=3,25
    3.3 ( 2.31 )
    4.9 ( 3.44 )
        Part 3 Month 6 n=5,15
    3.0 ( 2.12 )
    7.7 ( 4.82 )
    No statistical analyses for this end point

    Secondary: Ventilation use for Parts 1 and 3 and Parts 2 and 3 - FAS

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    End point title
    Ventilation use for Parts 1 and 3 and Parts 2 and 3 - FAS
    End point description
    BiBAP (bilevel positive airway pressure) ventilation is a 2 level breathing support which has a tube that connects to a mask. It provides a different level of air pressure for inhalation vs. exhalation, whereas a CPAP (continuous positive airway pressure) only pumps one level of air pressure but is also non-invasiive. Invasive ventilation is delivered via an endotracheal or tracheostomy tube. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration.
    End point type
    Secondary
    End point timeframe
    Baseline up to 82 months
    End point values
    Parts 1 & 3 Overall Parts 2 & 3 Overall
    Number of subjects analysed
    11
    15
    Units: participants
        Non-invasive ventilation - BiPAP
    9
    18
        Non-invasive ventilation - CPAP
    3
    2
        Invasive ventilation
    4
    5
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post last treatment up a maximum of 83 months.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    LMI070 24 mg/m2
    Reporting group description
    LMI070 24 mg/m2

    Reporting group title
    LMI070 12 mg/m2
    Reporting group description
    LMI070 12 mg/m2

    Reporting group title
    LMI070 6 mg/m2
    Reporting group description
    LMI070 6 mg/m2

    Reporting group title
    LMI070 0.625 mg/kg
    Reporting group description
    LMI070 0.625 mg/kg

    Reporting group title
    LMI070 60 mg/m2
    Reporting group description
    LMI070 60 mg/m2

    Reporting group title
    LMI070 2.5 mg/kg
    Reporting group description
    LMI070 2.5 mg/kg

    Reporting group title
    LMI070 48 mg/m2
    Reporting group description
    LMI070 48 mg/m2

    Serious adverse events
    LMI070 24 mg/m2 LMI070 12 mg/m2 LMI070 6 mg/m2 LMI070 0.625 mg/kg LMI070 60 mg/m2 LMI070 2.5 mg/kg LMI070 48 mg/m2
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 2 (100.00%)
    2 / 2 (100.00%)
    2 / 2 (100.00%)
    8 / 10 (80.00%)
    3 / 3 (100.00%)
    11 / 15 (73.33%)
    4 / 4 (100.00%)
         number of deaths (all causes)
    2
    2
    1
    1
    1
    2
    3
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    Vascular disorders
    Circulatory collapse
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    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
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Apnoea
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Atelectasis
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    1 / 3 (33.33%)
    1 / 15 (6.67%)
    2 / 4 (50.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchostenosis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngospasm
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Obstructive airways disorder
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachypnoea
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Pneumomediastinum
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Pulmonary haemorrhage
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Respiratory arrest
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    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
    0 / 0
    Respiratory distress
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    2 / 4 (50.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    2 / 10 (20.00%)
    2 / 3 (66.67%)
    2 / 15 (13.33%)
    2 / 4 (50.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 3
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    Investigations
    Ejection fraction decreased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    N-terminal prohormone brain natriuretic peptide increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 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
    0 / 0
    Oxygen saturation decreased
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    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
    0 / 0
    Respiratory syncytial virus test positive
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 1
    Rotavirus test positive
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Salmonella test positive
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Transaminases increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Ultrasound kidney abnormal
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Injury, poisoning and procedural complications
    Shunt malfunction
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Foreign body in gastrointestinal tract
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    2 / 10 (20.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    2 / 4 (50.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Left ventricular hypertrophy
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    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
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    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
    0 / 0
    Arrhythmia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Tachycardia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Nervous system disorders
    Hydrocephalus
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Ischaemic cerebral infarction
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Anaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    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
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Peptic ulcer haemorrhage
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Hepatobiliary disorders
    Hepatomegaly
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Renal and urinary disorders
    Renal tubular disorder
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Hypercalciuria
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Muscular weakness
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Infections and infestations
    Bronchiolitis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    2 / 15 (13.33%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Bronchitis bacterial
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea infectious
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Enterovirus infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    Gastroenteritis rotavirus
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Nasopharyngitis
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    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
    0 / 0
    Infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Otitis media
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    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
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 2 (50.00%)
    2 / 2 (100.00%)
    2 / 2 (100.00%)
    4 / 10 (40.00%)
    2 / 3 (66.67%)
    7 / 15 (46.67%)
    2 / 4 (50.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
    0 / 5
    0 / 6
    0 / 2
    0 / 13
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pneumococcal sepsis
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Parainfluenzae virus infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    2 / 15 (13.33%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    1 / 10 (10.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 1
    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
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Pseudomonas infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rhinovirus infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    2 / 4 (50.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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 / 1
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 10 (20.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 2 (100.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    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
    0 / 0
    Hypophagia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Malnutrition
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    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
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    LMI070 24 mg/m2 LMI070 12 mg/m2 LMI070 6 mg/m2 LMI070 0.625 mg/kg LMI070 60 mg/m2 LMI070 2.5 mg/kg LMI070 48 mg/m2
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    2 / 2 (100.00%)
    2 / 2 (100.00%)
    2 / 2 (100.00%)
    10 / 10 (100.00%)
    3 / 3 (100.00%)
    15 / 15 (100.00%)
    4 / 4 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Melanocytic naevus
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Vascular disorders
    Diastolic hypertension
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Cyanosis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Hypertension
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    3 / 10 (30.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    5
    0
    0
    0
    Hypotension
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Thrombosis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Surgical and medical procedures
    Tracheostomy
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Therapy cessation
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    General disorders and administration site conditions
    Granuloma
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    Asthenia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Catheter site haemorrhage
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Discomfort
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Fatigue
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    Hyperpyrexia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    0
    Hyperthermia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    4 / 15 (26.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    7
    0
    Malaise
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    Medical device pain
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Medical device site granuloma
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Pain
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Pyrexia
         subjects affected / exposed
    2 / 2 (100.00%)
    2 / 2 (100.00%)
    2 / 2 (100.00%)
    7 / 10 (70.00%)
    3 / 3 (100.00%)
    6 / 15 (40.00%)
    2 / 4 (50.00%)
         occurrences all number
    4
    11
    9
    19
    28
    16
    6
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Immune system disorders
    Allergy to arthropod bite
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Drug hypersensitivity
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Immunisation reaction
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    2 / 4 (50.00%)
         occurrences all number
    1
    1
    1
    0
    1
    0
    3
    Multiple allergies
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Reproductive system and breast disorders
    Genital rash
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Vulvovaginal dryness
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Vulvovaginal rash
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Choking
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    Asthma
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    Atelectasis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    Bronchiectasis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Bronchospasm
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Aspiration
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Chronic respiratory failure
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Cough
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    3 / 10 (30.00%)
    3 / 3 (100.00%)
    4 / 15 (26.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    3
    10
    6
    0
    Dysphonia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Dyspnoea
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Epistaxis
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    Nasal obstruction
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Increased bronchial secretion
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    3 / 3 (100.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    0
    Increased upper airway secretion
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    2 / 3 (66.67%)
    0 / 15 (0.00%)
    2 / 4 (50.00%)
         occurrences all number
    0
    0
    0
    0
    7
    0
    3
    Lung disorder
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Nasal congestion
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Nasal discomfort
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Hypoxia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    2 / 15 (13.33%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    2
    0
    Obstructive airways disorder
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Productive cough
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    1
    0
    Pulmonary fibrosis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Respiratory depression
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Respiratory disorder
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Respiratory distress
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    Respiratory failure
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 10 (20.00%)
    1 / 3 (33.33%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    2
    0
    0
    2
    1
    1
    0
    Respiratory tract inflammation
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Sputum discoloured
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    2 / 3 (66.67%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    Tachypnoea
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    1
    0
    Vasomotor rhinitis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Agitation
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Behaviour disorder
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Irritability
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    0
    1
    0
    0
    Restlessness
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    1
    Investigations
    Blood iron decreased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Blood creatinine decreased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    3 / 10 (30.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    3
    0
    1
    0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    2 / 15 (13.33%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    2
    0
    Blood alkaline phosphatase decreased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Blood albumin decreased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    5 / 10 (50.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    2 / 4 (50.00%)
         occurrences all number
    0
    0
    2
    9
    0
    0
    2
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    5 / 10 (50.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    5
    0
    0
    1
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    2 / 10 (20.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    2
    0
    1
    0
    Fungal test positive
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Electrocardiogram P pulmonale
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Crystal urine present
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 10 (20.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    C-reactive protein increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    1
    Body temperature increased
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    2 / 15 (13.33%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    0
    1
    5
    0
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    Blood potassium increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 10 (20.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    Blood potassium decreased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Blood parathyroid hormone decreased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Brain natriuretic peptide increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Haematocrit decreased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    4
    0
    0
    0
    0
    Haemoglobin decreased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    4
    1
    0
    2
    0
    Heart rate decreased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Heart rate increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    N-terminal prohormone brain natriuretic peptide increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    1
    0
    Reticulocyte count decreased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 2 (100.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    Oxygen saturation decreased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    Platelet count increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Red blood cell count decreased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    4
    0
    0
    0
    0
    Nerve conduction studies abnormal
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Transaminases increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    Troponin T increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Troponin increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    2
    0
    Ultrasound kidney abnormal
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Urine phosphorus increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Urine uric acid increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    Weight decreased
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    2 / 3 (66.67%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    1
    0
    0
    1
    3
    0
    2
    White blood cell count decreased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    White blood cells urine positive
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    4
    0
    0
    0
    Vitamin D decreased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    Exposure to SARS-CoV-2
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Femur fracture
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    3 / 15 (20.00%)
    1 / 4 (25.00%)
         occurrences all number
    1
    0
    0
    1
    0
    3
    1
    Fibula fracture
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Foot fracture
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Humerus fracture
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    1 / 10 (10.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    1
    1
    1
    0
    0
    Joint dislocation
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    1 / 10 (10.00%)
    1 / 3 (33.33%)
    2 / 15 (13.33%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    1
    1
    2
    1
    Lower limb fracture
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Subdural haematoma
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    Subdural haemorrhage
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Sunburn
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    Tibia fracture
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    2 / 3 (66.67%)
    1 / 15 (6.67%)
    1 / 4 (25.00%)
         occurrences all number
    1
    0
    0
    0
    2
    1
    1
    Upper limb fracture
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Tracheostomy malfunction
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    0
    0
    Congenital, familial and genetic disorders
    Dacryostenosis congenital
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Cryptorchism
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Developmental hip dysplasia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Hypertrophic cardiomyopathy
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Phimosis
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Plagiocephaly
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Cardiac disorders
    Myocarditis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Arrhythmia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Atrial tachycardia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Bradycardia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    Cardiac failure
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Pericardial effusion
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Right ventricular hypertrophy
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Sinus bradycardia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Sinus node dysfunction
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Supraventricular extrasystoles
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Tachycardia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 10 (20.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    1
    0
    Sinus tachycardia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    2 / 15 (13.33%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    1
    0
    2
    1
    Nervous system disorders
    Brain injury
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Cerebral atrophy
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Complex regional pain syndrome
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Glossopharyngeal nerve disorder
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    Headache
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    2
    0
    1
    0
    0
    Hydrocephalus
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Motor dysfunction
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    Facial paresis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    3 / 15 (20.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    0
    0
    1
    5
    0
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    Leukocytosis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    2 / 15 (13.33%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    2
    0
    Neutropenia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    3 / 10 (30.00%)
    1 / 3 (33.33%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    10
    1
    3
    0
    Lymphopenia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Monocytosis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 10 (20.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    1
    0
    Leukopenia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 10 (20.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    3
    0
    1
    0
    Pancytopenia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Polycythaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Reticulocytopenia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Thrombocytopenia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 10 (20.00%)
    1 / 3 (33.33%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    2
    1
    1
    0
    Thrombocytosis
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    4 / 10 (40.00%)
    0 / 3 (0.00%)
    3 / 15 (20.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    0
    8
    0
    8
    0
    White blood cell disorder
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    Ear and labyrinth disorders
    Tympanic membrane hyperaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Ear pain
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    2 / 3 (66.67%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    9
    0
    0
    Eye disorders
    Chalazion
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Astigmatism
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    1 / 3 (33.33%)
    3 / 15 (20.00%)
    1 / 4 (25.00%)
         occurrences all number
    1
    0
    0
    1
    1
    3
    1
    Blepharitis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Heterophoria
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Hypermetropia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Myopia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Ocular hyperaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Optic atrophy
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Strabismus
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Gastrointestinal disorders
    Aphthous ulcer
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Abdominal distension
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Abdominal pain
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    1
    0
    0
    0
    Anal fissure
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    Constipation
         subjects affected / exposed
    2 / 2 (100.00%)
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    7 / 10 (70.00%)
    2 / 3 (66.67%)
    3 / 15 (20.00%)
    0 / 4 (0.00%)
         occurrences all number
    3
    3
    7
    7
    6
    5
    0
    Dental cyst
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Diarrhoea
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    2 / 10 (20.00%)
    3 / 3 (100.00%)
    2 / 15 (13.33%)
    1 / 4 (25.00%)
         occurrences all number
    4
    2
    3
    3
    7
    3
    3
    Dyspepsia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    1
    0
    Dysphagia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Gastrointestinal pain
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    1
    0
    0
    0
    0
    0
    Faecaloma
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Flatulence
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    0
    1
    1
    0
    0
    Food poisoning
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Functional gastrointestinal disorder
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Erosive oesophagitis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    2
    0
    Gingival pain
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    0
    0
    Gingival swelling
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Haematochezia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Oesophagitis haemorrhagic
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Inguinal hernia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Malocclusion
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Nausea
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    1
    0
    Oesophagitis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Hiatus hernia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Regurgitation
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    Salivary hypersecretion
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Teething
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    2 / 3 (66.67%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    4
    0
    0
    Tongue disorder
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Toothache
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Vomiting
         subjects affected / exposed
    2 / 2 (100.00%)
    1 / 2 (50.00%)
    2 / 2 (100.00%)
    2 / 10 (20.00%)
    3 / 3 (100.00%)
    2 / 15 (13.33%)
    2 / 4 (50.00%)
         occurrences all number
    7
    3
    9
    3
    15
    10
    6
    Hepatobiliary disorders
    Hepatomegaly
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Hypertransaminasaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Skin and subcutaneous tissue disorders
    Hyperhidrosis
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    1
    0
    Eczema
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    2
    0
    1
    0
    Drug eruption
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Dermatitis diaper
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Dermatitis atopic
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    1 / 3 (33.33%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    1
    0
    Keratosis pilaris
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Decubitus ulcer
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Blister
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    1
    Perioral dermatitis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Papule
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Dermatitis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    1 / 3 (33.33%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    1
    0
    Urticaria
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Rash maculo-papular
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    2 / 10 (20.00%)
    2 / 3 (66.67%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    0
    2
    2
    1
    0
    Rash erythematous
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Rash
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    2 / 3 (66.67%)
    3 / 15 (20.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    0
    1
    5
    8
    1
    Pruritus
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Renal and urinary disorders
    Hypercalciuria
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Ketonuria
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    3 / 10 (30.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    7
    0
    2
    0
    Leukocyturia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    2
    0
    Nephrocalcinosis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Nephrolithiasis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Dysuria
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Proteinuria
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Calculus urinary
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Nephroptosis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Pyelocaliectasis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Urinary retention
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Musculoskeletal and connective tissue disorders
    Flank pain
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Arthralgia
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    Deformity thorax
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Foot deformity
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    1 / 4 (25.00%)
         occurrences all number
    1
    0
    1
    1
    0
    1
    1
    Fracture pain
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Joint contracture
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Joint swelling
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Muscular weakness
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    2 / 10 (20.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    1
    0
    6
    2
    1
    0
    2
    Rib deformity
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Osteolysis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Osteopenia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Osteoporosis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Pain in extremity
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Scoliosis
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    2 / 2 (100.00%)
    4 / 10 (40.00%)
    2 / 3 (66.67%)
    3 / 15 (20.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    2
    4
    2
    3
    0
    Infections and infestations
    Asymptomatic COVID-19
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Bacterial disease carrier
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Cellulitis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Bronchitis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    5 / 10 (50.00%)
    1 / 3 (33.33%)
    8 / 15 (53.33%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    9
    6
    10
    0
    Bronchitis bacterial
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    COVID-19
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    2 / 15 (13.33%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    2
    0
    Candida infection
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Bacterial rhinitis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Ear infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    1 / 10 (10.00%)
    1 / 3 (33.33%)
    1 / 15 (6.67%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    3
    1
    1
    1
    4
    Conjunctivitis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    2 / 10 (20.00%)
    1 / 3 (33.33%)
    3 / 15 (20.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    2
    1
    5
    0
    Cystitis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0
    Cytomegalovirus infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Dermatitis infected
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Gastroenteritis norovirus
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Eye infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Folliculitis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Fungal skin infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Gastroenteritis
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    2 / 2 (100.00%)
    0 / 10 (0.00%)
    2 / 3 (66.67%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    3
    0
    2
    0
    0
    Ear infection viral
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Gastroenteritis viral
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Gastrointestinal infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    Hordeolum
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Infected bite
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    4
    0
    0
    0
    0
    Infection
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Otitis externa
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    1
    0
    Medical device site infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    6 / 15 (40.00%)
    1 / 4 (25.00%)
         occurrences all number
    1
    1
    1
    0
    4
    8
    2
    Oral candidiasis
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Oral fungal infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Klebsiella infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Otitis media
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    1 / 10 (10.00%)
    1 / 3 (33.33%)
    1 / 15 (6.67%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    1
    1
    1
    1
    3
    Otitis media acute
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Pharyngitis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    2 / 15 (13.33%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    Pneumonia
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    1 / 15 (6.67%)
    1 / 4 (25.00%)
         occurrences all number
    1
    1
    2
    0
    3
    2
    1
    Pseudomonas infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Rhinitis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    2 / 10 (20.00%)
    3 / 3 (100.00%)
    4 / 15 (26.67%)
    2 / 4 (50.00%)
         occurrences all number
    0
    0
    2
    2
    7
    12
    4
    Rash pustular
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Respiratory syncytial virus infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Respiratory tract infection
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    3 / 10 (30.00%)
    2 / 3 (66.67%)
    3 / 15 (20.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    3
    1
    3
    13
    3
    0
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    2 / 10 (20.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    2
    0
    1
    0
    Pyuria
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Rhinovirus infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    1
    Roseola
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Skin bacterial infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Skin infection
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Staphylococcal infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 10 (20.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    1
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    4 / 10 (40.00%)
    3 / 3 (100.00%)
    3 / 15 (20.00%)
    2 / 4 (50.00%)
         occurrences all number
    0
    7
    5
    11
    17
    5
    5
    Urethritis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Urinary tract infection
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    2 / 10 (20.00%)
    3 / 3 (100.00%)
    2 / 15 (13.33%)
    0 / 4 (0.00%)
         occurrences all number
    7
    3
    1
    6
    9
    2
    0
    Varicella
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Viral infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Tonsillitis
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    0
    Vulvitis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Metabolism and nutrition disorders
    Feeding disorder
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Decreased appetite
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    3
    1
    0
    0
    0
    Failure to thrive
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 10 (20.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    1
    0
    Feeding intolerance
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Fluid intake reduced
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Hyperglycaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Hypoglycaemia
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    4
    0
    Hypophagia
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    0
    0
    0
    1
    0
    0
    Iron deficiency
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Malnutrition
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 10 (20.00%)
    0 / 3 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    1
    0
    Hyponatraemia
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    28 Nov 2014
    Clarified the phases of the study, the sequential enrollment of subjects into the cohorts. Provided clariication on the safety monitoring of the subjects after they received their first dose of study treatment. Correction of the study phase from Phase II to Phase I/II
    27 Feb 2015
    Clarifed the exclusion criteria, the dose limiting toxicities and the provisional dose levels. Revised the criteria for interruption and re-initiation of branaplam treatment based on the revision of the dose limiting toxicity (DLT) criteria.
    30 Nov 2015
    Iimplemented additional safety measures following an urgent safety measures (USM). Ophthalmologic monitoring was added as part of the safety monitoring plan. Implemented requests for modification from the independent data monitoring committee (DMC) following their review of the clinical safety data. Added a different and much less burdensome assessment to evaluate respiratory function, measurement of chest circumference during quiet breathing. Plans to increase the total number of subjects to be enrolled in Part 1 of the study up to approximately 30.
    31 Mar 2016
    Implemented additional cardiac monitoring following a second USM. Exclusion criterion #10 was expanded to exclude a broader range of cardiac disease. Dose modification rules were added for cardiac disorders and hypertension. Two higher dose levels (120 mg/m2 and 240 mg/m2), which exceeded the available preclinical toxicology exposure were removed. Measurement of quadriceps muscle thickness by ultrasound and the evaluation of exploratory biomarkers in hair and in urine were removed.
    31 Aug 2016
    Implemented additional safety monitoring following a third USM. Reduction of the Weekly dose of branaplam administered to all subjects having completed the initial 13 Weeks of treatment to 6 mg/m2. Addition of two following safety endpoints: neurologic examination and neurophysiologic examination to the primary objective. Correction of a discrepancy in secondary objective which indicated that branaplam pharmacokinetics were evaluated in serum instead of plasma samples. The CMAP which used to be optional was amended as mandatory for all subjects enrolled in the study.
    28 Apr 2017
    Implemented to allow resumption of enrollment in the ongoing study as agreed by the independent DMC. Part 2 of the study was modified to obtain additional safety and efficacy data with oral administration of up to 3 dose levels of branaplam, already tested in Part 1. Part 2 was to enroll approximately 30 subjects. The age of subjects at screening was restricted to 180 days of age. A minimum CHOP INTEND score of 15 was required at baseline and subjects were required to be able to feed orally for all nutritional needs and be greater than the 2nd percentile for weight on the standard growth curves for the country of origin.
    29 Dec 2017
    Implemented in all countries where the study was being conducted the changes made based on the request of the German Health Authority during their review of the Amended Protocol version v06.Added criteria used to decide interrupting and re-initiating treatment with branaplam in the event of thrombocytosis. The name of the Novartis department where serious adverse events (SAEs) need to be sent was changed. Updated Appendix 16.1.1-Protocol-Table 6-2 to include the dose conversion from BSA to weight for doses in Part 1 of the study.
    31 Oct 2018
    Ensured that the studied doses were clinically distinguishable and more efficiently investigated the branaplam dose-response relationship in conjunction with the data generated in Part 1. Several modifications to the inclusion and exclusion criteria. Clarified that Part 1 subjects followed the Extended treatment Schedule of Assessment and subjects enrolled in Part 2 could receive study treatment in a separate protocol.
    30 Apr 2019
    Provided subjects from Part 1 and Part 2 of this protocol the possibility for continuous treatment and long-term safety and efficacy follow up in the newly added Part 3 of the study. Study description for Part 3 provided. Eliminated assessments that were present in Parts 1 and 2 and which were not necessary for Part 3. Revised efficacy endpoints (CHOP INTEND to be collected up to 3 years of age, i.e. 36 months). Clarified and simplified the process of branaplam administration at home.
    28 Feb 2020
    Clarified the frequency of ophthalmology assessments in Part 3 of the study. Updated the possibility to have a dose increase to 2.5 mg/kg in Part 3 for subjects treated with 0.625 mg/kg dose from Part 2, if no further improvement becomes evident, or in case of disease progression at the discretion of investigator and after consultation with the sponsor.

    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.
    In alignment with the study objectives, safety and tolerability of branaplam irrespective of the dose, were analyzed according to the treatment group that participants were assigned at baseline irrespective of study dose or route of administration.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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