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    Clinical Trial Results:
    A Phase 2, Open Label, Multicenter Study to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of Sebelipase Alfa in Infants with Rapidly Progressive Lysosomal Acid Lipase Deficiency

    Summary
    EudraCT number
    2014-000533-22
    Trial protocol
    GB   IT   FI  
    Global end of trial date
    30 Oct 2018

    Results information
    Results version number
    v2(current)
    This version publication date
    18 Dec 2019
    First version publication date
    23 May 2019
    Other versions
    v1
    Version creation reason
    • Correction of full data set
    Updates made to align with presentation of study results on ClinicalTrials.gov.

    Trial information

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    Trial identification
    Sponsor protocol code
    LAL-CL08
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02193867
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Alexion Pharmaceuticals Inc.
    Sponsor organisation address
    121 Seaport Blvd., Boston, MA, United States, 02210
    Public contact
    European Clinical Trial Information, Alexion Pharmaceuticals Inc., +33 147100606, clinicaltrials.eu@alexion.com
    Scientific contact
    European Clinical Trial Information, Alexion Pharmaceuticals Inc., +33 147100606, clinicaltrials.eu@alexion.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
    30 Oct 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    30 Oct 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Oct 2018
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of the study was to evaluate the safety and tolerability of sebelipase alfa in infants with rapidly progressive lysosomal acid lipase deficiency.
    Protection of trial subjects
    This study was conducted in accordance with International Council on Harmonisation (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the countries in which the study was conducted.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    01 May 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 8
    Country: Number of subjects enrolled
    Finland: 1
    Country: Number of subjects enrolled
    United States: 1
    Worldwide total number of subjects
    10
    EEA total number of subjects
    9
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    1
    Infants and toddlers (28 days-23 months)
    9
    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
    A total of 6 sites were initiated, and participants were treated at 5 sites in 3 countries (United Kingdom [UK], United States [US], Finland). One study site in the US was initiated but did not screen or treat any participants.

    Pre-assignment
    Screening details
    The study consisted of a screening period of up to 3 weeks. Participants who met all eligibility criteria were enrolled, treated, and analysed.

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

    Arms
    Arm title
    Open-Label Sebelipase Alfa
    Arm description
    All participants initiated once weekly (qw) intravenous (IV) infusions with sebelipase alfa at a dose of 1 milligram/kilogram (mg/kg) qw. A participant who met protocol defined dose escalation criteria at a dose of 1 mg/kg qw could be considered for a dose escalation to 3 mg/kg qw. If a participant continued to meet dose escalation criteria after at least 4 infusions at a dose of 3 mg/kg qw, the participant could be considered for a further dose escalation to 5 mg/kg qw. Under country-specific provisions (UK only), participants could be considered for a further dose escalation to 7.5 mg/kg qw if a thorough case review indicated that a participant continued to have evidence of disease progression at a dose of 5 mg/kg qw. All dose escalations were contingent upon acceptable safety and tolerability of preceding infusions and were undertaken by mutual agreement of the Investigator and Sponsor and after approval by an independent safety committee.
    Arm type
    Experimental

    Investigational medicinal product name
    Sebelipase Alfa
    Investigational medicinal product code
    Other name
    SBC-102
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    All participants initiated treatment with sebelipase alfa at dose of 1 mg/kg qw. Dose escalations to 3 mg/kg qw, 5 mg/kg qw, or 7.5 mg/kg qw (UK only) were permitted for individual participants who met pre-defined dose escalation criteria. A change in dose frequency and dose reductions were permitted in the event of poor tolerability. Participants who did not tolerate a dose of 3 mg/kg qw could receive a dose reduction to 1 mg/kg qw. A participant who could not tolerate a dose of 1 mg/kg qw, despite measures taken to manage infusion-associated reactions, was to be discontinued from the study. All dose reductions were undertaken after consultation between the Investigator and Sponsor and, where appropriate, the safety committee.

    Number of subjects in period 1
    Open-Label Sebelipase Alfa
    Started
    10
    Received At Least 1 Dose Of Study Drug
    10
    Completed 18 Months Of Treatment
    8
    Completed
    6
    Not completed
    4
         Death
    2
         Sponsor Study Termination
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Open-Label Sebelipase Alfa
    Reporting group description
    All participants initiated once weekly (qw) intravenous (IV) infusions with sebelipase alfa at a dose of 1 milligram/kilogram (mg/kg) qw. A participant who met protocol defined dose escalation criteria at a dose of 1 mg/kg qw could be considered for a dose escalation to 3 mg/kg qw. If a participant continued to meet dose escalation criteria after at least 4 infusions at a dose of 3 mg/kg qw, the participant could be considered for a further dose escalation to 5 mg/kg qw. Under country-specific provisions (UK only), participants could be considered for a further dose escalation to 7.5 mg/kg qw if a thorough case review indicated that a participant continued to have evidence of disease progression at a dose of 5 mg/kg qw. All dose escalations were contingent upon acceptable safety and tolerability of preceding infusions and were undertaken by mutual agreement of the Investigator and Sponsor and after approval by an independent safety committee.

    Reporting group values
    Open-Label Sebelipase Alfa Total
    Number of subjects
    10 10
    Age categorical
    Units: Subjects
        In utero
    0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0
        Newborns (0-27 days)
    1 1
        Infants and toddlers (28 days-23 months)
    9 9
        Children (2-11 years)
    0 0
        Adolescents (12-17 years)
    0 0
        Adults (18-64 years)
    0 0
        From 65-84 years
    0 0
        85 years and over
    0 0
    Age continuous
    Units: months
        arithmetic mean (standard deviation)
    4.13 ± 2.859 -
    Gender categorical
    Units: Subjects
        Female
    5 5
        Male
    5 5
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska native
    1 1
        Asian
    6 6
        White
    1 1
        Egyptian
    1 1
        Turkish Kurdish
    1 1

    End points

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    End points reporting groups
    Reporting group title
    Open-Label Sebelipase Alfa
    Reporting group description
    All participants initiated once weekly (qw) intravenous (IV) infusions with sebelipase alfa at a dose of 1 milligram/kilogram (mg/kg) qw. A participant who met protocol defined dose escalation criteria at a dose of 1 mg/kg qw could be considered for a dose escalation to 3 mg/kg qw. If a participant continued to meet dose escalation criteria after at least 4 infusions at a dose of 3 mg/kg qw, the participant could be considered for a further dose escalation to 5 mg/kg qw. Under country-specific provisions (UK only), participants could be considered for a further dose escalation to 7.5 mg/kg qw if a thorough case review indicated that a participant continued to have evidence of disease progression at a dose of 5 mg/kg qw. All dose escalations were contingent upon acceptable safety and tolerability of preceding infusions and were undertaken by mutual agreement of the Investigator and Sponsor and after approval by an independent safety committee.

    Subject analysis set title
    Full Analysis Set (FAS)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    All participants who received any amount of sebelipase alfa (1.0, 3.0, 5.0, or 7.5 mg/kg qw) during the study and where applicable, met end-point criteria.

    Primary: Participants Experiencing Severe Treatment-emergent Adverse Events (TEAEs)

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    End point title
    Participants Experiencing Severe Treatment-emergent Adverse Events (TEAEs) [1]
    End point description
    The number of participants experiencing severe TEAEs is presented for participants who received sebelipase alfa in this open-label study. Adverse events were obtained through spontaneous reporting or elicited by specific questioning or examination of the participant’s parent or legal guardian. An adverse event was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant, whether or not causally related to administration of study drug. Adverse event severity was graded by the Investigator as mild, moderate, or severe based on definitions developed from Clinical Data Interchange Standards Consortium Study Data Tabulation Model standard terminology v3.1.1. Adverse events reporting was from the date of informed consent until completion of the follow-up visit at approximately 30 days after the last dose of study drug. A summary of all serious and other nonserious AEs regardless of causality is located in the Adverse Events section.
    End point type
    Primary
    End point timeframe
    Screening through Month 37
    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: Quantitative statistical analyses were not conducted on any of the reported safety data.
    End point values
    Open-Label Sebelipase Alfa
    Number of subjects analysed
    10 [2]
    Units: Participants
    7
    Notes
    [2] - FAS
    No statistical analyses for this end point

    Secondary: Percentage Of Participants Surviving To 12, 18, 24, And 36 Months Of Age

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    End point title
    Percentage Of Participants Surviving To 12, 18, 24, And 36 Months Of Age
    End point description
    The percentage of participants in the FAS who survived to 12, 18, 24, and 36 months of age. The exact confidence interval was calculated using the Clopper-Pearson method. Participants with unknown survival status at the age specified in the analysis were excluded. At 36 months, there were 2 participants who were alive and still on study who had not yet reached the age specified in the analysis. As such, these participants were excluded from the calculation of percent surviving.
    End point type
    Secondary
    End point timeframe
    Baseline through Month 12, Month 18, Month 24, and Month 36
    End point values
    Open-Label Sebelipase Alfa
    Number of subjects analysed
    10
    Units: percentage of participants
    number (confidence interval 95%)
        12 Months
    90 (55.5 to 99.7)
        18 Months
    80 (44.4 to 97.5)
        24 Months
    80 (44.4 to 97.5)
        36 Months
    75 (34.9 to 96.8)
    No statistical analyses for this end point

    Secondary: Median Age At Death

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    End point title
    Median Age At Death
    End point description
    Age at death for participants who died during the study. All deaths were assessed by the Investigator as unrelated to study drug.
    End point type
    Secondary
    End point timeframe
    Baseline through Month 36
    End point values
    Open-Label Sebelipase Alfa
    Number of subjects analysed
    2 [3]
    Units: Months
        median (full range (min-max))
    9.33 (4.9 to 13.8)
    Notes
    [3] - FAS
    No statistical analyses for this end point

    Secondary: Change From Baseline In Percentiles For Weight For Age (WFA) At 12, 24, And 36 Months

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    End point title
    Change From Baseline In Percentiles For Weight For Age (WFA) At 12, 24, And 36 Months
    End point description
    This end point evaluated the effects of sebelipase alfa on growth by measuring the changes from baseline in percentiles for WFA. Percentiles for WFA were summarized as observed values by visit. Baseline was defined as the last available assessment prior to the first infusion of sebelipase alfa.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12, Month 24, and Month 36
    End point values
    Open-Label Sebelipase Alfa
    Number of subjects analysed
    9 [4]
    Units: Percentile
    median (full range (min-max))
        Month 12 (N=8)
    27.760 (1.34 to 67.58)
        Month 24 (N=8)
    41.276 (7.54 to 63.77)
        Month 36 (N=5)
    59.310 (36.39 to 72.51)
    Notes
    [4] - FAS
    No statistical analyses for this end point

    Secondary: Number Of Participants With Stunting, Wasting, Or Underweight At Baseline, 12, 24, And 36 Months

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    End point title
    Number Of Participants With Stunting, Wasting, Or Underweight At Baseline, 12, 24, And 36 Months
    End point description
    The number of participants who met criteria for the following 3 dichotomous indicators of under nutrition were reported. These indicators included the following: 1. Stunting was defined as at least 2 standard deviations below the median for length-for-age/height-for-age. 2. Wasting was defined as wasting at least 2 standard deviations below the median for weight-for-length/weight-for-height. 3. Underweight was defined as at least 2 standard deviations below the median for WFA.
    End point type
    Secondary
    End point timeframe
    Baseline to Month 12, Month 24, and Month 36
    End point values
    Open-Label Sebelipase Alfa
    Number of subjects analysed
    10 [5]
    Units: Participants
        Stunting, Baseline (N=9)
    4
        Stunting, Month 12 (N=8)
    0
        Stunting, Month 24 (N=8)
    0
        Stunting, Month 36 (N=5)
    0
        Wasting, Baseline (N=9)
    5
        Wasting, Month 12 (N=8)
    0
        Wasting, Month 24 (N=8)
    0
        Wasting, Month 36 (N=5)
    0
        Underweight, Baseline (N=10)
    6
        Underweight, Month 12 (N=8)
    0
        Underweight, Month 24 (N=8)
    0
        Underweight, Month 36 (N=5)
    0
    Notes
    [5] - FAS
    No statistical analyses for this end point

    Secondary: Change From Baseline In Serum Transaminases (ALT And AST) At Month 12, 24, And 36

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    End point title
    Change From Baseline In Serum Transaminases (ALT And AST) At Month 12, 24, And 36
    End point description
    This end point evaluated the effects of sebelipase alfa on liver function by measuring the change from baseline in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) at months 12, 24, and 36. Results are reported in units/liter (U/L).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12, Month 24, and Month 36
    End point values
    Open-Label Sebelipase Alfa
    Number of subjects analysed
    10 [6]
    Units: U/L
    median (full range (min-max))
        ALT: Month 12 (N=7)
    0 (-175 to 66)
        ALT: Month 24 (N=7)
    14.0 (-207 to 80)
        ALT: Month 36 (N=4)
    -42.0 (-224 to 6)
        AST: Month 12 (N=6)
    -33.5 (-322 to 8)
        AST: Month 24 (N=5)
    -4.0 (-90 to 36)
        AST: Month 36 (N=3)
    -101.0 (-351 to -9)
    Notes
    [6] - FAS
    No statistical analyses for this end point

    Secondary: Change From Baseline In Serum Ferritin At Month 12, 24, And 36

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    End point title
    Change From Baseline In Serum Ferritin At Month 12, 24, And 36
    End point description
    The median change in the inflammatory marker serum ferritin from Baseline to Months 12, 24, and 36 is presented. The number of participants analyzed reflects only those from the FAS who had both a baseline value and a value at the indicated timepoint (Months 12, 24, and 36). Results are reported in micrograms (ug)/L.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12, Month 24, and Month 36
    End point values
    Open-Label Sebelipase Alfa
    Number of subjects analysed
    2 [7]
    Units: ug/L
    median (full range (min-max))
        Month 12 (N=1)
    -2957.00 (-2957.0 to -2957.0)
        Month 24 (N=2)
    -1722.00 (-2984.0 to -460.0)
        Month 36 (N=0)
    0 (0 to 0)
    Notes
    [7] - Participants in the FAS who had both a baseline value and a value at the indicated timepoint.
    No statistical analyses for this end point

    Secondary: Number Of Participants Achieving And Maintaining Transfusion-free Hemoglobin Normalization (TFHN)

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    End point title
    Number Of Participants Achieving And Maintaining Transfusion-free Hemoglobin Normalization (TFHN)
    End point description
    The number of participants achieving and maintaining TFHN are presented. For TFHN to be achieved, the participant had to meet the following criteria: 1. Two post baseline measurements of hemoglobin, at least 4 weeks apart, were above the age-adjusted lower limit of normal (LLN); 2. No known additional measurements of hemoglobin were below the age-adjusted LLN during the (minimum) 4 week period; 3. No transfusions were administered to the participant during the (minimum) 4 week period, or for 2 weeks prior to the first hemoglobin measurement in the (minimum) 4 week period. If all 3 criteria were met, a participant was considered to have achieved TFHN on the date of the first hemoglobin assessment in the 4 week period. A participant was considered to have maintained TFHN if he/she was transfusion free at Week 6 and had no abnormally low hemoglobin levels (levels below the age adjusted LLN) beginning at Week 8 of the study and continuing for at least 13 weeks (3 months).
    End point type
    Secondary
    End point timeframe
    Baseline through Month 36
    End point values
    Open-Label Sebelipase Alfa
    Number of subjects analysed
    10 [8]
    Units: Participants
        Achieved TFHN
    7
        Maintained TFHN
    0
    Notes
    [8] - FAS
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Screening (up to 21 days prior to start of treatment) to Month 37 (approximately 30 days after the last dose of study drug).
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    Sebelipase Alfa: 1.0 mg/kg qw
    Reporting group description
    This reporting group is based on the FAS and includes AEs with onset during the administration of IV treatment of sebelipase alfa at a dose of 1.0 mg/kg qw. All 10 participants in the FAS received sebelipase alfa at a dose of 1.0 mg/kg qw.

    Reporting group title
    Sebelipase Alfa: 3.0 mg/kg qw
    Reporting group description
    This reporting group is based on the FAS and includes AEs with onset during the administration of IV treatment of sebelipase alfa at a dose of 3.0 mg/kg qw. Nine of the 10 participants in the FAS received sebelipase alfa at a dose of 3.0 mg/kg qw.

    Reporting group title
    Sebelipase Alfa: 5.0 mg/kg qw
    Reporting group description
    This reporting group is based on the FAS and includes AEs with onset during the administration of IV treatment of sebelipase alfa at a dose of 5.0 mg/kg qw. Seven of the 10 participants in the FAS received sebelipase alfa at a dose of 5.0 mg/kg qw.

    Reporting group title
    Sebelipase Alfa: 7.5 mg/kg qw
    Reporting group description
    This reporting group is based on the FAS and includes AEs with onset during the administration of IV treatment of sebelipase alfa at a dose of 7.5 mg/kg qw (UK only). One of the 10 participants in the FAS received sebelipase alfa at a dose of 7.5 mg/kg qw.

    Serious adverse events
    Sebelipase Alfa: 1.0 mg/kg qw Sebelipase Alfa: 3.0 mg/kg qw Sebelipase Alfa: 5.0 mg/kg qw Sebelipase Alfa: 7.5 mg/kg qw
    Total subjects affected by serious adverse events
         subjects affected / exposed
    8 / 10 (80.00%)
    8 / 9 (88.89%)
    7 / 7 (100.00%)
    1 / 1 (100.00%)
         number of deaths (all causes)
    1
    0
    1
    0
         number of deaths resulting from adverse events
    Vascular disorders
    Bloody discharge
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Flushing
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Poor venous access
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Superior vena cava occlusion
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Venoocclusive disease
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Bone marrow transplant
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 1 (100.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Catheter site haemorrhage
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Complication associated with device
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypothermia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 10 (10.00%)
    6 / 9 (66.67%)
    3 / 7 (42.86%)
    1 / 1 (100.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 12
    1 / 4
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Irritability
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Skull fracture
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transfusion reaction
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Body temperature fluctuation
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Body temperature increased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug specific antibody absent
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sapovirus test positive
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Pericardial effusion
    Additional description: The single occurrence of pericardial effusion in the 1.0 mg/kg qw group lead to death and was assessed by the Investigator as unrelated to study drug.
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    2 / 10 (20.00%)
    2 / 9 (22.22%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    5 / 5
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Adenoidal hypertrophy
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 7 (28.57%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sleep apnoea syndrome
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachypnoea
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsillar hypertrophy
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Abdominal lymphadenopathy
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Histiocytosis haematophagic
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 10 (0.00%)
    4 / 9 (44.44%)
    2 / 7 (28.57%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 6
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lip swelling
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malabsorption
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tongue erythema
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 10 (10.00%)
    5 / 9 (55.56%)
    4 / 7 (57.14%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 8
    1 / 8
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Liver disorder
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Nephrotic syndrome
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oliguria
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperhidrosis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urticaria
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Device occlusion
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Embedded device
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Feeding disorder
         subjects affected / exposed
    1 / 10 (10.00%)
    3 / 9 (33.33%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abscess bacterial
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Catheter site infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Croup infectious
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    2 / 7 (28.57%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    3 / 7 (42.86%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis viral
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    2 / 10 (20.00%)
    6 / 9 (66.67%)
    3 / 7 (42.86%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis adenovirus
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis norovirus
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis rotavirus
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 7 (28.57%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lice infestation
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Parainfluenzae virus infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory syncytial virus bronchiolitis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    1 / 1 (100.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rhinovirus infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Scrotal infection
         subjects affected / exposed [1]
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 4 (25.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
    Additional description: The single occurrence of sepsis in the 5.0 mg/kg qw group lead to death and was assessed by the Investigator as unrelated to study drug.
         subjects affected / exposed
    2 / 10 (20.00%)
    2 / 9 (22.22%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Staphylococcal skin infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stoma site infection
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 9 (22.22%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis streptococcal
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 10 (10.00%)
    3 / 9 (33.33%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: Only male participants were exposed to this adverse event.
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Sebelipase Alfa: 1.0 mg/kg qw Sebelipase Alfa: 3.0 mg/kg qw Sebelipase Alfa: 5.0 mg/kg qw Sebelipase Alfa: 7.5 mg/kg qw
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    9 / 10 (90.00%)
    9 / 9 (100.00%)
    7 / 7 (100.00%)
    1 / 1 (100.00%)
    Vascular disorders
    Hyperaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hypertension
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    1 / 1 (100.00%)
         occurrences all number
    2
    1
    1
    1
    Hypotension
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Lymphodema
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Microangiopathy
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Poor venous access
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Superior vena cava occlusion
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Skin papilloma
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Immune system disorders
    Allergy to animal
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Anaphylactic reaction
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Drug hypersensitivity
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Hypersensitivity
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    2
    0
    0
    General disorders and administration site conditions
    Catheter site bruise
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Catheter site discharge
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Catheter site erythema
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 9 (22.22%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    1
    2
    2
    0
    Catheter site extravasation
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Catheter site granuloma
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    2
    1
    0
    Catheter site swelling
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Complication associated with device
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Crying
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Face oedema
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Feeling cold
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hypertrophy
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hypothermia
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 9 (22.22%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    2
    2
    0
    0
    Inflammation
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Injection site erythema
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Mass
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Mucosal inflammation
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    3 / 7 (42.86%)
    0 / 1 (0.00%)
         occurrences all number
    3
    1
    3
    0
    Oedema
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 1 (100.00%)
         occurrences all number
    0
    0
    0
    1
    Oedema peripheral
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    2
    0
    1
    0
    Pain
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    2 / 7 (28.57%)
    0 / 1 (0.00%)
         occurrences all number
    0
    2
    2
    0
    Pyrexia
         subjects affected / exposed
    7 / 10 (70.00%)
    7 / 9 (77.78%)
    5 / 7 (71.43%)
    1 / 1 (100.00%)
         occurrences all number
    15
    43
    36
    5
    Swelling
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Vaccination site pain
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Vessel puncture site discharge
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    2 / 10 (20.00%)
    2 / 9 (22.22%)
    1 / 7 (14.29%)
    1 / 1 (100.00%)
         occurrences all number
    2
    3
    1
    1
    Drug abuse
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Irritability
         subjects affected / exposed
    3 / 10 (30.00%)
    4 / 9 (44.44%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    3
    5
    0
    0
    Restlessness
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Staring
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Stress
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Reproductive system and breast disorders
    Vaginal haemorrhage
         subjects affected / exposed [2]
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    2
    2
    0
    Drug administration error
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Fall
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Gastrostomy tube site complication
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Head injury
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Laceration
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Ligament sprain
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Overdose
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Procedural pain
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    2
    1
    0
    Scar
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Skin abrasion
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Stoma site erythema
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    2
    1
    0
    Stoma site extravasation
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Stoma site haemorrhage
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Stoma site hypergranulation
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    3
    1
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    2
    1
    0
    Alpha 1 foetoprotein increased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Alpha-1 anti-trypsin increased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Antibody test positive
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Bacterial test positive
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Beta-2 glycoprotein antibody
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Blood albumin decreased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Blood aldosterone decreased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Blood aldosterone increased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Blood alkaline phosphatase decreased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Blood calcium decreased
         subjects affected / exposed
    2 / 10 (20.00%)
    2 / 9 (22.22%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    2
    3
    0
    0
    Blood cholesterol increased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Blood fibrinogen decreased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Blood fibrinogen increased
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Blood glucose fluctuation
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Blood glucose increased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Blood iron decreased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Blood parathyroid hormone
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Blood potassium decreased
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 9 (22.22%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Blood pressure abnormal
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    4
    0
    0
    0
    Blood pressure increased
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    2 / 7 (28.57%)
    0 / 1 (0.00%)
         occurrences all number
    2
    2
    2
    0
    Blood sodium decreased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Blood triglycerides decreased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Blood triglycerides increased
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    2
    1
    0
    Blood urea decreased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Blood urea increased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Blood uric acid decreased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Body temperature
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Body temperature abnormal
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Body temperature decreased
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Body temperature increased
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    1
    2
    4
    0
    Brucella test positive
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    C-reactive protein increased
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    2
    3
    5
    0
    Cardiac murmur
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Cortisol increased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Drug specific antibody
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Drug specific antibody present
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    1 / 1 (100.00%)
         occurrences all number
    0
    0
    1
    1
    Faecal calprotectin increased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Fibrin D dimer increased
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastric fluid analysis abnormal
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Heart rate increased
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    2
    1
    1
    0
    High density lipoprotein decreased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Human rhinovirus test positive
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Liver function test abnormal
         subjects affected / exposed
    2 / 10 (20.00%)
    2 / 9 (22.22%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    2
    2
    0
    0
    Low density lipoprotein increased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Nasogastric output abnormal
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Neutrophil count increased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Nitrite urine present
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Norovirus test positive
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Osmolar gap increased
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Oxygen saturation decreased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Parvovirus B19 test positive
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Procalcitonin increased
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Protein total decreased
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 9 (0.00%)
    2 / 7 (28.57%)
    0 / 1 (0.00%)
         occurrences all number
    2
    0
    2
    0
    Prothrombin level decreased
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Prothrombin time prolonged
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Renal function test abnormal
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Renin decreased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Renin increased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Respiratory rate increased
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    2
    1
    1
    0
    Serum ferritin increased
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 9 (22.22%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    1
    2
    1
    0
    Staphylococcus test positive
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Transaminases increased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Vitamin A decreased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Vitamin D decreased
         subjects affected / exposed
    3 / 10 (30.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    3
    1
    1
    0
    Vitamin E decreased
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    3
    1
    1
    0
    Weight decreased
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Cardiac disorders
    Bradycardia
         subjects affected / exposed
    3 / 10 (30.00%)
    2 / 9 (22.22%)
    2 / 7 (28.57%)
    0 / 1 (0.00%)
         occurrences all number
    4
    2
    3
    0
    Cardiac septal hypertrophy
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Cardiomyopathy
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Cyanosis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Left ventricular dilatation
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Tachycardia
         subjects affected / exposed
    5 / 10 (50.00%)
    6 / 9 (66.67%)
    3 / 7 (42.86%)
    1 / 1 (100.00%)
         occurrences all number
    8
    13
    5
    3
    Congenital, familial and genetic disorders
    Atrial septal defect
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Chimerism
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Chromosomal deletion
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hydrocele
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Adenoidal hypertrophy
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Asthma
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Cough
         subjects affected / exposed
    3 / 10 (30.00%)
    4 / 9 (44.44%)
    4 / 7 (57.14%)
    0 / 1 (0.00%)
         occurrences all number
    6
    19
    8
    0
    Epistaxis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    3 / 7 (42.86%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    6
    0
    Nasal congestion
         subjects affected / exposed
    2 / 10 (20.00%)
    3 / 9 (33.33%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    2
    5
    0
    0
    Nasal oedema
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Pharyngeal erythema
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Pleural effusion
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Productive cough
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pulmonary oedema
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Respiratory acidosis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Respiratory distress
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 9 (11.11%)
    3 / 7 (42.86%)
    0 / 1 (0.00%)
         occurrences all number
    2
    1
    8
    0
    Rhinorrhoea
         subjects affected / exposed
    1 / 10 (10.00%)
    3 / 9 (33.33%)
    4 / 7 (57.14%)
    0 / 1 (0.00%)
         occurrences all number
    1
    6
    6
    0
    Sneezing
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Tachypnoea
         subjects affected / exposed
    0 / 10 (0.00%)
    3 / 9 (33.33%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    4
    0
    0
    Tonsillar erythema
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Tonsillar hypertrophy
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Use of accessory respiratory muscles
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Wheezing
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 9 (22.22%)
    2 / 7 (28.57%)
    0 / 1 (0.00%)
         occurrences all number
    2
    2
    2
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 10 (20.00%)
    2 / 9 (22.22%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    2
    2
    4
    0
    Febrile neutropenia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 7 (28.57%)
    1 / 1 (100.00%)
         occurrences all number
    0
    0
    3
    1
    Hypochromasia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Leukocytosis
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    2
    2
    2
    0
    Leukopenia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Lymph node calcification
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Lymphadenopathy
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    2 / 7 (28.57%)
    0 / 1 (0.00%)
         occurrences all number
    1
    1
    2
    0
    Lymphocytosis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Neutropenia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Microcytosis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Neutrophilia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    3
    0
    0
    Thrombocytopenia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Thrombocytosis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    3
    0
    Nervous system disorders
    Petit mal epilepsy
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Somnolence
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Eye disorders
    Eye discharge
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    2 / 7 (28.57%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    2
    0
    Eyelid oedema
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    1
    1
    1
    0
    Eyelid rash
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Ocular hyperaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    3
    0
    0
    Abdominal distension
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 9 (0.00%)
    2 / 7 (28.57%)
    0 / 1 (0.00%)
         occurrences all number
    3
    0
    2
    0
    Abdominal pain
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    1 / 1 (100.00%)
         occurrences all number
    0
    1
    1
    1
    Abdominal pain upper
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    6
    1
    0
    Aphthous ulcer
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Chapped lips
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Constipation
         subjects affected / exposed
    2 / 10 (20.00%)
    2 / 9 (22.22%)
    2 / 7 (28.57%)
    0 / 1 (0.00%)
         occurrences all number
    2
    5
    4
    0
    Diarrhoea
         subjects affected / exposed
    4 / 10 (40.00%)
    5 / 9 (55.56%)
    5 / 7 (71.43%)
    0 / 1 (0.00%)
         occurrences all number
    12
    23
    29
    0
    Faeces hard
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Flatulence
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Gastritis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    2
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Haematemesis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Infantile spitting up
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Inguinal hernia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Intestinal obstruction
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Lip dry
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Lip swelling
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Teething
         subjects affected / exposed
    0 / 10 (0.00%)
    3 / 9 (33.33%)
    2 / 7 (28.57%)
    0 / 1 (0.00%)
         occurrences all number
    0
    5
    2
    0
    Vomiting
         subjects affected / exposed
    5 / 10 (50.00%)
    6 / 9 (66.67%)
    4 / 7 (57.14%)
    0 / 1 (0.00%)
         occurrences all number
    11
    15
    11
    0
    Renal and urinary disorders
    Proteinuria
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Renal impairment
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Urinary retention
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hepatic calcification
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dermatitis diaper
         subjects affected / exposed
    3 / 10 (30.00%)
    3 / 9 (33.33%)
    3 / 7 (42.86%)
    0 / 1 (0.00%)
         occurrences all number
    5
    9
    4
    0
    Dry skin
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    2 / 7 (28.57%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    4
    0
    Eczema
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    2 / 7 (28.57%)
    0 / 1 (0.00%)
         occurrences all number
    2
    1
    2
    0
    Erythema
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hyperhidrosis
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    5
    1
    0
    0
    Pigmentation disorder
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    1
    2
    1
    0
    Pruritus
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 9 (22.22%)
    2 / 7 (28.57%)
    1 / 1 (100.00%)
         occurrences all number
    1
    2
    2
    5
    Pruritus generalised
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Rash
         subjects affected / exposed
    2 / 10 (20.00%)
    2 / 9 (22.22%)
    2 / 7 (28.57%)
    0 / 1 (0.00%)
         occurrences all number
    2
    4
    4
    0
    Rash generalised
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Rash erythematous
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Rash maculo-papular
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Rash papular
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Rash pruritic
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Red man syndrome
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Scar pain
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Seborrhoeic dermatitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Skin disorder
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    1 / 1 (100.00%)
         occurrences all number
    1
    1
    0
    1
    Skin exfoliation
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Skin irritation
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Swelling face
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Urticaria
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    2
    2
    3
    0
    Product issues
    Device breakage
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Device dislocation
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    2
    1
    0
    Device infusion issue
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Device occlusion
         subjects affected / exposed
    0 / 10 (0.00%)
    3 / 9 (33.33%)
    4 / 7 (57.14%)
    0 / 1 (0.00%)
         occurrences all number
    0
    4
    4
    0
    Musculoskeletal and connective tissue disorders
    Joint swelling
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    4
    0
    1
    0
    Electrolyte imbalance
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Feeding disorder
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Fluid overload
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Hyperglycaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hypernatraemia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 9 (22.22%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Hypocalcaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    3 / 9 (33.33%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    4
    1
    0
    Hypoglycaemia
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    2
    1
    4
    0
    Hypokalaemia
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    2
    1
    1
    0
    Hyponatraemia
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 9 (0.00%)
    2 / 7 (28.57%)
    0 / 1 (0.00%)
         occurrences all number
    2
    0
    2
    0
    Hypophagia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hypophosphataemia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Hyposideraemia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hypovitaminosis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    2 / 7 (28.57%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Hypovolaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Iron deficiency
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Malnutrition
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    3
    1
    0
    0
    Metabolic acidosis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Vitamin A deficiency
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Vitamin D deficiency
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    2 / 7 (28.57%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Vitamin E deficiency
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Infections and infestations
    Abscess limb
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Adenoviral upper respiratory infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Bacteraemia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 1 (100.00%)
         occurrences all number
    0
    0
    0
    1
    Candida infection
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Candida nappy rash
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Catheter site abscess
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Cytomegalovirus viraemia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Device related infection
         subjects affected / exposed
    1 / 10 (10.00%)
    4 / 9 (44.44%)
    2 / 7 (28.57%)
    1 / 1 (100.00%)
         occurrences all number
    1
    5
    5
    1
    Device related sepsis
         subjects affected / exposed
    2 / 10 (20.00%)
    2 / 9 (22.22%)
    2 / 7 (28.57%)
    0 / 1 (0.00%)
         occurrences all number
    2
    2
    3
    0
    Enterococcal infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Escherichia urinary tract infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Exanthema subitum
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Eye infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Eye infection bacterial
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Fungal infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Gastroenteritis
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    2
    1
    1
    0
    Gastroenteritis norovirus
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Gastroenteritis rotavirus
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastroenteritis sapovirus
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hordeolum
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Influenza
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 9 (22.22%)
    2 / 7 (28.57%)
    0 / 1 (0.00%)
         occurrences all number
    4
    2
    4
    0
    Oral candidiasis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Otitis media
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    2
    2
    0
    Parainfluenzae virus infection
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Parechovirus infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Pneumonia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Respiratory syncytial virus bronchiolitis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Respiratory tract infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Rhinitis
         subjects affected / exposed
    2 / 10 (20.00%)
    4 / 9 (44.44%)
    2 / 7 (28.57%)
    0 / 1 (0.00%)
         occurrences all number
    2
    8
    7
    0
    Rhinovirus infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    2 / 7 (28.57%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    4
    0
    Sepsis
         subjects affected / exposed
    2 / 10 (20.00%)
    4 / 9 (44.44%)
    1 / 7 (14.29%)
    1 / 1 (100.00%)
         occurrences all number
    2
    4
    7
    1
    Skin infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Staphylococcal infection
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Stoma site infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Tonsillitis
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    3 / 7 (42.86%)
    0 / 1 (0.00%)
         occurrences all number
    1
    2
    3
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Viral infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    1
    1
    1
    0
    Adenovirus infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Notes
    [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: Only female participants were exposed to this adverse event.

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 Dec 2014
    Removed the requirement that a participant receive at least 4 infusions at a dose of 1 mg/kg qw before being considered for dose escalation to 3 mg/kg qw, provided that the participant still met other pre-defined dose escalation criteria based on clinical response.
    07 Jan 2016
    Modified to allow for dose escalation to 7.5 mg/kg qw at UK sites only. Dose escalation to 7.5 mg/kg qw was to be implemented only after a thorough case review, and following mutual agreement by the Investigator and Sponsor and approval by the safety committee.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported

    Online references

    http://www.ncbi.nlm.nih.gov/pubmed/23348766
    http://www.ncbi.nlm.nih.gov/pubmed/26312827
    http://www.ncbi.nlm.nih.gov/pubmed/28179030
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