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    Clinical Trial Results:
    A Phase Ib/IIa, Randomised, Double Blind, Parallel Group, Placebo Controlled, Multicentre Study to Assess the Safety and Efficacy of Expanded Cx611 Allogeneic Adipose-derived Stem Cells (eASCs) for the Intravenous Treatment of Adult Patients With Severe Community-acquired Bacterial Pneumonia and Admitted to the Intensive Care Unit

    Summary
    EudraCT number
    		 2015-002994-39
    Trial protocol
    		 ES   BE   LT   GB   FR   IT  
    Global end of trial date
    07 Jul 2020

    Results information
    Results version number
    		 v2(current)
    This version publication date
    18 May 2022
    First version publication date
    23 Jul 2021
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Results need to be updated to match to revised CTgov results due to NIH comments.

    Trial information

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    Trial identification
    Sponsor protocol code
    Cx611-0204
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03158727
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Takeda
    Sponsor organisation address
    95 Hayden Avenue, Lexington, United States, MA 02421
    Public contact
    Study Director, Takeda, TrialDisclosures@takeda.com
    Scientific contact
    Study Director, Takeda, TrialDisclosures@takeda.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    07 Jul 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Jul 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The Primary purpose of this study is to assess the safety profile of two allogeneic Cx611 80 milliliter (mL) infusions administered through a central line within 3 days (on Days 1 and 3) at a dose of 160 million cells each (320 million cells total) and also to monitor any adverse event and potential immunological host responses against the administered cells during 90 days of follow-up after the first infusion.
    Protection of trial subjects
    All study subjects were required to read and sign an Informed Consent Form.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    30 Jan 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Belgium: 19
    Country: Number of subjects enrolled
    Spain: 45
    Country: Number of subjects enrolled
    Lithuania: 1
    Country: Number of subjects enrolled
    France: 18
    Worldwide total number of subjects
    83
    EEA total number of subjects
    83
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    40
    From 65 to 84 years
    43
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Subjects took part in the study at 20 investigative sites in Belgium, France, Lithuania, and Spain from 30 January 2017 to 07 July 2020.

    Pre-assignment
    Screening details
    		 Adult subjects with severe community-acquired bacterial pneumonia (sCABP) and admitted to the intensive care unit (ICU) were enrolled in 1 of the 2 treatment groups to receive Cx611 or placebo on Days 1 and 3.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Subjects received standard of care (SoC) therapy followed by 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received SoC therapy followed by 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.

    Arm title
    		 Cx611 160 mL
    Arm description
    		 Subjects received SoC therapy followed by two 80 mL central line infusions of Cx611, intravenously, on Days 1 and 3 at a fixed dose of 160 million eASCs (320 million cells total).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cx611
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received SoC therapy followed by two 80 mL central line infusions of Cx611, intravenously, on Days 1 and 3 at a fixed dose of 160 million eASCs (320 million cells total).

    Number of subjects in period 1
    		Placebo Cx611 160 mL
    Started
    41
    42
    Completed
    25
    23
    Not completed
    16
    19
         Adverse event, serious fatal
    11
    12
         Consent withdrawn by subject
    2
    6
         Visit 11 not done by mistake
    -
    1
         Subject doesn't want go back to hospital for visit
    2
    -
         Lost to follow-up
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received standard of care (SoC) therapy followed by 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.

    Reporting group title
    Cx611 160 mL
    Reporting group description
    		 Subjects received SoC therapy followed by two 80 mL central line infusions of Cx611, intravenously, on Days 1 and 3 at a fixed dose of 160 million eASCs (320 million cells total).

    Reporting group values
    		 Placebo Cx611 160 mL Total
    Number of subjects
    		 41 42 83
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 17 23 40
        From 65-84 years
    		 24 19 43
        85 years and over
    		 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 63.4 ( 10.43 ) 61.1 ( 11.24 ) -
    Sex: Female, Male
    Units: subjects
        Female
    		 15 14 29
        Male
    		 26 28 54
    Race/Ethnicity, Customized
    Units: Subjects
        Caucasian
    		 31 28 59
        Asian/Oriental
    		 1 0 1
        Hispanic
    		 1 1 2
        Latino
    		 2 1 3
        Unknown
    		 6 12 18
    Region of Enrollment
    Units: Subjects
        Belgium
    		 12 7 19
        Spain
    		 23 22 45
        Lithuania
    		 0 1 1
        France
    		 6 12 18

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received standard of care (SoC) therapy followed by 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.

    Reporting group title
    Cx611 160 mL
    Reporting group description
    		 Subjects received SoC therapy followed by two 80 mL central line infusions of Cx611, intravenously, on Days 1 and 3 at a fixed dose of 160 million eASCs (320 million cells total).

    Primary: Number of Subjects Reporting one or More Treatment-emergent Adverse Events (TEAEs)

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    End point title
    		 Number of Subjects Reporting one or More Treatment-emergent Adverse Events (TEAEs) [1]
    End point description
    The safety population included all randomised subjects who received at least one dose of the study treatment.
    End point type
    Primary
    End point timeframe
    Baseline up to Day 90
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: subjects
    37
    40
    No statistical analyses for this end point

    Primary: Number of Subjects With Adverse Events of Special Interest (AESI)

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    End point title
    		 Number of Subjects With Adverse Events of Special Interest (AESI) [2]
    End point description
    AESIs are predefined adverse events (AEs) that required close monitoring and prompt reporting to the sponsor. Protocol-specific AEs considered as AESI for this study are thromboembolic events and hypersensitivity reactions such as anaphylaxis. The safety population included all randomised subjects who received at least one dose of the study treatment.
    End point type
    Primary
    End point timeframe
    Baseline up to Day 90
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: subjects
    9
    7
    No statistical analyses for this end point

    Primary: Number of Subjects With Hypersensitivity Reactions

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    End point title
    		 Number of Subjects With Hypersensitivity Reactions [3]
    End point description
    Hypersensitivity reactions included anaphylaxis (changes in systolic and diastolic blood pressure, core temperature, respiratory rate [non-ventilated subjects], heart rate), episodes of skin reactions and signs and symptoms of respiratory distress, which require therapeutic intervention including drugs and/or changes in mechanical ventilation setting. Number of subjects with hypersensitivity reactions were reported for this outcome measure. The safety population included all randomised subjects who received at least one dose of the study treatment.
    End point type
    Primary
    End point timeframe
    Baseline up to Day 90
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: subjects
    1
    0
    No statistical analyses for this end point

    Primary: Number of Subjects With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters on Day 1

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    End point title
    		 Number of Subjects With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters on Day 1 [4]
    End point description
    The safety population included all randomised subjects who received at least one dose of the study treatment.
    End point type
    Primary
    End point timeframe
    Day 1
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: subjects
    3
    7
    No statistical analyses for this end point

    Primary: Number of Subjects With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters on Day 3

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    End point title
    		 Number of Subjects With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters on Day 3 [5]
    End point description
    The safety population included all randomised subjects who received at least one dose of the study treatment.
    End point type
    Primary
    End point timeframe
    Day 3
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: subjects
    5
    4
    No statistical analyses for this end point

    Primary: Number of Subjects With Markedly Abnormal Laboratory Values

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    End point title
    		 Number of Subjects With Markedly Abnormal Laboratory Values [6]
    End point description
    The safety population included all randomised subjects who received at least one dose of the study treatment.
    End point type
    Primary
    End point timeframe
    Baseline up to Day 90
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: subjects
    0
    0
    No statistical analyses for this end point

    Primary: Number of Subjects With Anti-human Leukocyte Antigen Complex (Anti-HLA)/Donor Antibodies At Day 1, 14, and 90

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    End point title
    		 Number of Subjects With Anti-human Leukocyte Antigen Complex (Anti-HLA)/Donor Antibodies At Day 1, 14, and 90 [7]
    End point description
    The safety population included all randomised subjects who received at least one dose of the study treatment. Here, "overall number of subjects analyzed" are those who were evaluable for this outcome measure.
    End point type
    Primary
    End point timeframe
    At Days 1, 14, and 90
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: subjects
        Anti-HLA/Donor Antibodies at Day 1 (n=37, 40)
    6
    4
        Anti-HLA/Donor Antibodies at Day 14 (n=36, 32)
    4
    5
        Anti-HLA/Donor Antibodies at Day 90 (n=28, 21)
    4
    4
    No statistical analyses for this end point

    Secondary: Mechanical Ventilation and Vasopressors Treatment-free Days

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    End point title
    		 Mechanical Ventilation and Vasopressors Treatment-free Days
    End point description
    Subjects with sCABP suffer either a respiratory failure that requires invasive mechanical ventilation and/or a severe hypotension that requires vasopressors. Number of days when subjects were alive and free from mechanical ventilation and vasopressors were reported. The safety population included all randomised subjects who received at least one dose of the study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 28
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: days
        median (full range (min-max))
    19.0 (0 to 27)
    13.5 (0 to 25)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Alive and Free of Both Mechanical Ventilation and Vasopressors at Day 29

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    End point title
    		 Percentage of Subjects Alive and Free of Both Mechanical Ventilation and Vasopressors at Day 29
    End point description
    Subjects with sCABP suffer either a respiratory failure that requires invasive mechanical ventilation and/or a severe hypotension that requires vasopressors. Percentage of subjects who were alive and free of both mechanical ventilation and vasopressors at Day 29 were reported. The safety population included all randomised subjects who received at least one dose of the study treatment.
    End point type
    Secondary
    End point timeframe
    Day 29
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: percentage of subjects
        number (not applicable)
    78.0
    64.3
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Alive and Free of Mechanical Ventilation at Day 29

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    End point title
    		 Percentage of Subjects Alive and Free of Mechanical Ventilation at Day 29
    End point description
    The safety population included all randomised subjects who received at least one dose of the study treatment.
    End point type
    Secondary
    End point timeframe
    Day 29
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: percentage of subjects
        number (not applicable)
    78.0
    66.7
    No statistical analyses for this end point

    Secondary: Number of Ventilator Free Days (VeFD)

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    End point title
    		 Number of Ventilator Free Days (VeFD)
    End point description
    VeFD are defined as one point for each day during the measurement period that subjects are both alive and free from mechanical ventilation. The safety population included all randomised subjects who received at least one dose of the study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 28
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: days
        median (full range (min-max))
    19.0 (0 to 28)
    14.0 (0 to 28)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Alive and Free of Vasopressors at Day 29

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    End point title
    		 Percentage of Subjects Alive and Free of Vasopressors at Day 29
    End point description
    The safety population included all randomised subjects who received at least one dose of the study treatment.
    End point type
    Secondary
    End point timeframe
    Day 29
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: percentage of subjects
        number (not applicable)
    85.4
    76.2
    No statistical analyses for this end point

    Secondary: Number of Vasopressor Treatment-free Days (VaFD)

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    End point title
    		 Number of Vasopressor Treatment-free Days (VaFD)
    End point description
    VaFD over 28 days defined as one point for each day during the measurement period that subjects are both alive and free of vasopressors. The safety population included all randomised subjects who received at least one dose of the study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 28
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: days
        median (full range (min-max))
    24.0 (0 to 28)
    23.5 (0 to 28)
    No statistical analyses for this end point

    Secondary: Time to end of Invasive Mechanical Ventilation

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    End point title
    		 Time to end of Invasive Mechanical Ventilation
    End point description
    Time in days, from the start date of invasive mechanical ventilation to the first stop date of invasive mechanical ventilation (that is, first time the subject ends mechanical ventilation), or death. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported. Here, "overall number of subjects analyzed" are those who were evaluable for this outcome measure. The safety population included all randomised subjects who received at least one dose of the study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 29
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    33
    39
    Units: days
        median (confidence interval 95%)
    7.7 (4.6 to 11.5)
    8.3 (4.6 to 12.4)
    No statistical analyses for this end point

    Secondary: Time to end of Invasive and/or Non-invasive Mechanical Ventilation

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    End point title
    		 Time to end of Invasive and/or Non-invasive Mechanical Ventilation
    End point description
    Time in days, from the start date of invasive or non-invasive mechanical ventilation to the first stop date of invasive or non-invasive mechanical ventilation (that is, first time the subject ends mechanical ventilation), or death. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported. Here, "overall number of participants analyzed" are those who were evaluable for this outcome measure. The safety population included all randomised subjects who received at least one dose of the study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 29
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    33
    39
    Units: days
        median (confidence interval 95%)
    6.3 (3.3 to 10.3)
    4.7 (2.9 to 8.3)
    No statistical analyses for this end point

    Secondary: Time to end of Vasopressors Treatment

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    End point title
    		 Time to end of Vasopressors Treatment
    End point description
    Time in days, from the start date of vasopressors treatment to the first stop date of vasopressors treatment (that is, first time the subject ends vasopressors treatment), or death. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported. Here, "overall number of participants analyzed" are those who were evaluable for this outcome measure. The safety population included all randomised subjects who received at least one dose of the study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 29
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    33
    34
    Units: days
        median (confidence interval 95%)
    2.1 (1.4 to 3.0)
    2.0 (1.0 to 2.4)
    No statistical analyses for this end point

    Secondary: Time to sCABP Clinical Cure

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    End point title
    		 Time to sCABP Clinical Cure
    End point description
    Cure is defined as complete resolution of pneumonia signs and symptoms present at baseline, no new symptoms or complications attributable to the pneumonia. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported. The safety population included all randomised subjects who received at least one dose of the study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 29
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: days
        median (confidence interval 95%)
    13.0 (10.0 to 16.0)
    9.5 (8.0 to 14.0)
    No statistical analyses for this end point

    Secondary: Duration of Antibiotic Treatment

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    End point title
    		 Duration of Antibiotic Treatment
    End point description
    The safety population included all randomised subjects who received at least one dose of the study treatment. Here, "overall number of subjects analyzed" are those who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 29
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    39
    38
    Units: days
        median (full range (min-max))
    9.0 (2 to 29)
    8.0 (1 to 29)
    No statistical analyses for this end point

    Secondary: 28-day All-cause Mortality

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    End point title
    		 28-day All-cause Mortality
    End point description
    The safety population included all randomised subjects who received at least one dose of the study treatment.
    End point type
    Secondary
    End point timeframe
    Day 28
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: subjects
    6
    8
    No statistical analyses for this end point

    Secondary: 28-day sCABP-associated Mortality

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    End point title
    		 28-day sCABP-associated Mortality
    End point description
    The safety population included all randomised subjects who received at least one dose of the study treatment.
    End point type
    Secondary
    End point timeframe
    Day 28
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: subjects
    0
    1
    No statistical analyses for this end point

    Secondary: Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90

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    End point title
    		 Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90
    End point description
    Survival data for percentage of subjects at Baseline and at Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 was assessed and reported. The safety population included all randomised subjects who received at least one dose of the study treatment.
    End point type
    Secondary
    End point timeframe
    At Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: percentage of subjects
    number (confidence interval 95%)
        Baseline
    100.0 (100.0 to 100.0)
    100.0 (100.0 to 100.0)
        Day 10
    95.1 (81.9 to 98.8)
    88.1 (73.7 to 94.9)
        Day 20
    87.5 (72.6 to 94.6)
    80.7 (65.0 to 89.8)
        Day 30
    85.0 (69.5 to 93.0)
    80.7 (65.0 to 89.8)
        Day 40
    77.0 (60.4 to 87.3)
    80.7 (65.0 to 89.8)
        Day 50
    77.0 (60.4 to 87.3)
    75.3 (58.9 to 85.9)
        Day 60
    77.0 (60.4 to 87.3)
    75.3 (58.9 to 85.9)
        Day 70
    77.0 (60.4 to 87.3)
    75.3 (58.9 to 85.9)
        Day 80
    77.0 (60.4 to 87.3)
    75.3 (58.9 to 85.9)
        Day 90
    77.0 (60.4 to 87.3)
    71.5 (54.0 to 83.3)
    No statistical analyses for this end point

    Secondary: Time to Discharge From Intensive Care Unit (ICU)

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    End point title
    		 Time to Discharge From Intensive Care Unit (ICU)
    End point description
    Time to discharge from ICU was defined, in days, as the time between informed consent date and the date of discharge from the ICU. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported. The safety population included all randomised subjects who received at least one dose of the study treatment. Here, "overall number of subjects analyzed" are those who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 730
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    41
    Units: days
        median (confidence interval 95%)
    11.1 (7.1 to 14.9)
    13.0 (7.2 to 16.2)
    No statistical analyses for this end point

    Secondary: Time to Discharge From Hospital

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    End point title
    		 Time to Discharge From Hospital
    End point description
    Time to discharge from hospital was defined, in days, as the time between informed consent date and the date of discharge from the hospital. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported. The safety population included all randomised subjects who received at least one dose of the study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 730
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: days
        median (confidence interval 95%)
    19.2 (14.4 to 30.0)
    18.3 (13.2 to 25.7)
    No statistical analyses for this end point

    Secondary: Length of Stay (LOS) in ICU and Hospital After Randomization

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    End point title
    		 Length of Stay (LOS) in ICU and Hospital After Randomization
    End point description
    The safety population included all randomised subjects who received at least one dose of the study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 730
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: days
    median (full range (min-max))
        Length of stay in ICU
    11.1 (1 to 54)
    12.3 (0 to 121)
        Length of stay in Hospital
    19.2 (1 to 70)
    19.3 (1 to 186)
    No statistical analyses for this end point

    Secondary: Number of ICU-free Days

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    End point title
    		 Number of ICU-free Days
    End point description
    ICU-free days will be defined as the number of days during which the subject was not in ICU, starting from the randomization date, to Day 29, or day of discontinuation. The safety population included all randomised subjects who received at least one dose of the study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 29
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: days
        median (full range (min-max))
    14.0 (0 to 26)
    5.5 (0 to 24)
    No statistical analyses for this end point

    Secondary: Number of Subjects Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment

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    End point title
    		 Number of Subjects Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment
    End point description
    Number of subjects with chest X-ray assessment compared to the previous assessment were assessed and reported. Number of subjects are reported who showed Comparison of previous X-ray data is reported on the basis of improvement, remission, stabilization, and worsening when comparison of X-rays was performed to previous X-ray data. Cumulative data is reported only for subjects who were assessed from Day 8-10. The safety population included all randomised subjects who received at least one dose of the study treatment. Here, "overall number of subjects analyzed" are those who were evaluable for this outcome measure. Here, "number analyzed" are the subjects who were evaluable for the outcome measure at given time points.
    End point type
    Secondary
    End point timeframe
    Days 1, 2, 3, 4, 5, 6, 7, 8-10, 14, 29
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: subjects
        Improvement at Day 1 (n=9,10)
    0
    0
        Remission at Day 1 (n=9,10)
    0
    0
        Stabilization at Day 1 (n=9,10)
    7
    6
        Worsening at Day 1 (n=9,10)
    2
    4
        Improvement at Day 2 (n=34, 31)
    9
    6
        Remission at Day 2 (n=34, 31)
    0
    0
        Stabilization at Day 2 (n=34, 31)
    17
    17
        Worsening at Day 2 (n=34, 31)
    8
    8
        Improvement at Day 3 (n=37, 30)
    19
    8
        Remission at Day 3 (n=37, 30)
    0
    1
        Stabilization at Day 3 (n=37, 30)
    17
    17
        Worsening at Day 3 (n=37, 30)
    1
    4
        Improvement at Day 4 (n=30, 31)
    14
    8
        Remission at Day 4 (n=30, 31)
    1
    3
        Stabilization at Day 4 (n=30, 31)
    15
    12
        Worsening at Day 4 (n=30, 31)
    0
    8
        Improvement at Day 5 (n=20, 24)
    5
    8
        Remission at Day 5 (n=20, 24)
    2
    2
        Stabilization at Day 5 (n=20, 24)
    7
    9
        Worsening at Day 5 (n=20, 24)
    6
    5
        Improvement at Day 6 (n=29, 26)
    11
    12
        Remission at Day 6 (n=29, 26)
    1
    2
        Stabilization at Day 6 (n=29, 26)
    15
    10
        Worsening at Day 6 (n=29, 26)
    2
    2
        Improvement at Day 7 (n=18, 22)
    8
    8
        Remission at Day 7 (n=18, 22)
    0
    0
        Stabilization at Day 7 (n=18, 22)
    7
    11
        Worsening at Day 7 (n=18, 22)
    3
    3
        Improvement at Days 8-10 (n=27, 22)
    8
    9
        Remission at Days 8-10 (n=27, 22)
    3
    3
        Stabilization at Days 8-10 (n=27, 22)
    11
    7
        Worsening at Days 8-10 (n=27, 22)
    5
    3
        Improvement at Day 14 (n=21, 15)
    10
    10
        Remission at Day 14 (n=21, 15)
    1
    1
        Stabilization at Day 14 (n=21, 15)
    5
    3
        Worsening at Day 14 (n=21, 15)
    5
    1
        Improvement at Day 29 (n=9, 14)
    3
    6
        Remission at Day 29 (n=9, 14)
    3
    2
        Stabilization at Day 29 (n=9, 14)
    2
    4
        Worsening at Day 29 (n=9, 14)
    1
    2
    No statistical analyses for this end point

    Secondary: Number of Subjects Requiring Mechanical Ventilation or Non-invasive Ventilation Twelve Hours After the Second Investigational Medicinal Product (IMP) Infusion

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    End point title
    		 Number of Subjects Requiring Mechanical Ventilation or Non-invasive Ventilation Twelve Hours After the Second Investigational Medicinal Product (IMP) Infusion
    End point description
    The safety population included all randomised subjects who received at least one dose of the study treatment.
    End point type
    Secondary
    End point timeframe
    Day 3: 0 to 12 hours post-IMP infusion
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: subjects
        Count of Participants
    31
    37
    No statistical analyses for this end point

    Secondary: Number of Subjects Using Rescue Antibiotics

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    End point title
    		 Number of Subjects Using Rescue Antibiotics
    End point description
    Any new intravenous antibiotic for CABP indication that is started after Day 1 and before Day 29 was considered a rescue antibiotic. The safety population included all randomised subjects who received at least one dose of the study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 29
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: subjects
    28
    32
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Pneumonia Recurrence or Reinfection After Clinical Cure

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    End point title
    		 Percentage of Subjects With Pneumonia Recurrence or Reinfection After Clinical Cure
    End point description
    Pneumonia recurrence is defined as a new acute clinical episode of pneumonia, after clinical cure of the episode that qualified the subject for the study, based on the presence of two relevant signs (fever, tachypnoea, leukocytosis, or hypoxemia) and radiographic findings of new pulmonary infiltrate/s or clinically significant worsening of previous ones. If a bacterial pathogen isolated in the recurrent episode is phenotypically different from the one isolated in the previous episode this will be considered as reinfection. The safety population included all randomized subjects who received at least one dose of the study treatment. Here, "overall number of subjects analyzed" are those who were evaluable for this outcome measure. Here, "number analyzed" are the subjects who were evaluable for the outcome measure at given time points.
    End point type
    Secondary
    End point timeframe
    Days 14, 29, and 90
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    36
    33
    Units: percentage of subjects
    number (not applicable)
        Day 14: Recurrence (n=36, 33)
    5.6
    0
        Day 14: Reinfection (n=36, 33)
    8.3
    6.1
        Day 29: Recurrence (n=32, 30)
    0
    3.3
        Day 29: Reinfection (n=32, 30)
    0
    0
        Day 90: Recurrence (n=28, 25)
    0
    0
        Day 90: Reinfection (n=28, 25)
    0
    0
    No statistical analyses for this end point

    Secondary: Time to Recurrence or Reinfection of Pneumonia After Clinical Cure at sCABP Clinical Response Assessments

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    End point title
    		 Time to Recurrence or Reinfection of Pneumonia After Clinical Cure at sCABP Clinical Response Assessments
    End point description
    Pneumonia recurrence:New acute clinical episode of pneumonia, after clinical cure of episode that qualified subject for study, based on presence of 2 relevant signs (fever, tachypnoea, leukocytosis/hypoxemia) and radiographic findings of new pulmonary infiltrates or clinically significant worsening of previous ones. If bacterial pathogen isolated in recurrent episode is phenotypically different from one isolated in previous episode this will be considered as reinfection. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported. Safety population included all randomized subjects who received at least one dose of the study treatment. Here, "overall number of subjects analyzed" are those who were evaluable for this endpoint. Here “99999” refers to median and confidence interval, which was not estimable since none of the values were above lower limit of quantification(LLOQ) and therefore we have added 9999 as space fillers.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 90
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    34
    32
    Units: days
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Time to Death

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    End point title
    		 Time to Death
    End point description
    Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported. Median and 95% confidence interval could not be calculated since an insufficient number of subjects had an event. The safety population included all randomized subjects who received at least one dose of the study treatment. Here “99999” refers to the median and confidence interval, which was not estimable since none of the values were above lower limit of quantification (LLOQ) and therefore we have added 99999 as space fillers.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 90
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: days
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Change From Baseline in Sepsis-related Organ Failure Assessment (SOFA) Score During Stay at ICU

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    End point title
    		 Change From Baseline in Sepsis-related Organ Failure Assessment (SOFA) Score During Stay at ICU
    End point description
    The total SOFA Score is a composite of six sub scores representing the degree of dysfunction of six organ systems: Respiratory, Cardiovascular, Liver, Renal, Coagulation and Central Nervous System. Each organ system sub score ranges from 0 to 4 points. The total SOFA Score is the sum of the six-organ system sub scores. Accordingly, the total SOFA Score may range from a minimum score of 0 to a maximum score of 24. Higher scores indicate greater degree of dysfunction. The safety population included all randomized subjects who received at least one dose of the study treatment. Here, "overall number of subjects analyzed" are those who were evaluable for this outcome measure. Here, "number analyzed" are the subjects who were evaluable for the outcome measure at given time points.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 29
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    40
    42
    Units: Score on scale
    arithmetic mean (standard deviation)
        Baseline (n=40, 42)
    7.9 ( 2.39 )
    8.5 ( 3.01 )
        Change at Day 29 (n=16, 24)
    -6.1 ( 3.30 )
    -5.7 ( 3.95 )
    No statistical analyses for this end point

    Secondary: Number of Subjects With sCABP Clinical Response Visit at Days 8-10, 14, and 29

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    End point title
    		 Number of Subjects With sCABP Clinical Response Visit at Days 8-10, 14, and 29
    End point description
    Cure:complete resolution of pneumonia at baseline(BL),no new symptoms/complications attributable to pneumonia. Non-response-failure related/unrelated to pneumonia:persistence/progression of BL signs/symptoms of pneumonia;BL radiographic abnormalities after atleast 2days of treatment or development of new pulmonary/extra pulmonary findings consistent with active infection/development of new pulmonary infection/extrapulmonary infection requiring antimicrobial therapy/persistence/progression of BL signs/symptoms of severe sepsis/development of new signs/symptoms of severe sepsis/death.Non-response-failure unrelated to pneumonia:any cause of clinical response failure that in investigator's judgement is unrelated to index pneumonia.Indeterminate:extenuating circumstances precluding classification to one of the above.Safety population:all randomized subjects who received atleast one dose of study treatment.Here"number analyzed"are subjects who were evaluable for this OM at given time point.
    End point type
    Secondary
    End point timeframe
    Days 8 to 10, 14, and 29
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: subjects
        Days 8 to 10 (Cure) (n=38, 36)
    18
    21
        Days 8 to 10 (Failure not resulting in death) (n=3
    8
    6
        Days 8 to 10 (Indeterminate) (n=38, 36)
    11
    9
        Days 8 to 10 (Missing) (n=38, 36)
    1
    0
        Day 14 (Cure) (n=36, 33)
    24
    24
        Day 14 (Failure not resulting in death) (n=36, 33)
    5
    4
        Day 14 (Indeterminate) (n=36, 33)
    6
    4
        Day 14 (Missing) (n=36, 33)
    1
    1
        Day 29 (Cure) (n=32, 30)
    30
    26
        Day 29 (Failure not resulting in death) (n=32, 30)
    1
    1
        Day 29 (Indeterminate) (n=32, 30)
    0
    3
        Day 29 (Missing) (n=32, 30)
    1
    0
    No statistical analyses for this end point

    Secondary: Change in the Ratio of the Partial Pressure of Oxygen to the Fraction of Inspired Oxygen (PaO2/FiO2 Ratio)

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    End point title
    		 Change in the Ratio of the Partial Pressure of Oxygen to the Fraction of Inspired Oxygen (PaO2/FiO2 Ratio)
    End point description
    The safety population included all randomised subjects who received at least one dose of the study treatment. Here "number analyzed" n are the subjects who were evaluable for this outcome measure at given categories.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 7
    End point values
    		 Placebo Cx611 160 mL
    Number of subjects analysed
    41
    42
    Units: P/F ratio
    arithmetic mean (standard deviation)
        Baseline (n=41, 42)
    131.6 ( 55.14 )
    278.6 ( 981.67 )
        Change at Day 7 (n=30, 33)
    74.6 ( 97.20 )
    78.4 ( 68.57 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Treatment-emergent adverse events are adverse events that started from the signature of the informed consent (Baseline) up to Day 730
    Adverse event reporting additional description
    At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the subject or observed by the investigator was recorded, irrespective of the relation to study treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received SoC therapy followed by central line infusions of placebo-matching Cx611, intravenously, on Days 1 and 3.

    Reporting group title
    Cx611 160 mL
    Reporting group description
    		 Subjects received SoC therapy followed by two 80 mL central line infusions of Cx611, intravenously, on Days 1 and 3 at a fixed dose of 160 million eASCs (320 million cells total).

    Serious adverse events
    		 Placebo Cx611 160 mL
    Total subjects affected by serious adverse events
         subjects affected / exposed
    20 / 41 (48.78%)
    24 / 42 (57.14%)
         number of deaths (all causes)
    12
    13
         number of deaths resulting from adverse events
    Vascular disorders
    Arterial thrombosis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 41 (0.00%)
    2 / 42 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Jugular vein thrombosis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shock
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous thrombosis limb
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Coronary artery bypass
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mitral valve replacement
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Fibrosis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    4 / 41 (9.76%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 3
    0 / 1
    Immune system disorders
    Anaphylactic shock
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hypercapnia
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    2 / 41 (4.88%)
    2 / 42 (4.76%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Obstructive airways disorder
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory acidosis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    3 / 41 (7.32%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspiration bronchial
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Hip fracture
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial thrombosis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular dissociation
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 41 (2.44%)
    2 / 42 (4.76%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    Cardiac failure congestive
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Cardiogenic shock
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Nervous system disorders
    Cerebral artery embolism
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cerebrovascular accident
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intensive care unit acquired weakness
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Haemolysis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastric ulcer
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus paralytic
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Subileus
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Acute hepatic failure
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hepatic failure
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Ischaemic hepatitis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Urticaria
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 41 (0.00%)
    3 / 42 (7.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Rhabdomyolysis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bronchopulmonary aspergillosis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterococcal bacteraemia
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 41 (0.00%)
    2 / 42 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia klebsiella
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate infection
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 41 (0.00%)
    2 / 42 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Toxic shock syndrome
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tracheobronchitis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Urosepsis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Gout
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Placebo Cx611 160 mL
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    41 / 41 (100.00%)
    42 / 42 (100.00%)
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    5 / 41 (12.20%)
    1 / 42 (2.38%)
         occurrences all number
    5
    1
    Hypertension
         subjects affected / exposed
    2 / 41 (4.88%)
    6 / 42 (14.29%)
         occurrences all number
    2
    6
    Hypotension
         subjects affected / exposed
    1 / 41 (2.44%)
    2 / 42 (4.76%)
         occurrences all number
    1
    2
    Ischaemia
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 42 (2.38%)
         occurrences all number
    1
    1
    Phlebitis
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 42 (2.38%)
         occurrences all number
    1
    1
    Venous thrombosis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Generalised oedema
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Device related thrombosis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Hyperthermia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Hypothermia
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 42 (0.00%)
         occurrences all number
    2
    0
    Malaise
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Oedema
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Oedema peripheral
         subjects affected / exposed
    1 / 41 (2.44%)
    3 / 42 (7.14%)
         occurrences all number
    1
    3
    Puncture site haemorrhage
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Pyrexia
         subjects affected / exposed
    1 / 41 (2.44%)
    2 / 42 (4.76%)
         occurrences all number
    1
    2
    Reproductive system and breast disorders
    Penile oedema
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Atelectasis
         subjects affected / exposed
    2 / 41 (4.88%)
    3 / 42 (7.14%)
         occurrences all number
    2
    3
    Acute respiratory distress syndrome
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Bronchospasm
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 42 (2.38%)
         occurrences all number
    1
    1
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 42 (2.38%)
         occurrences all number
    1
    1
    Cough
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Epistaxis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Haemothorax
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Hypercapnia
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Hypoxia
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 42 (2.38%)
         occurrences all number
    1
    1
    Pleural effusion
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 42 (2.38%)
         occurrences all number
    1
    1
    Pharyngeal haemorrhage
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Pleuritic pain
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Pneumothorax
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 42 (2.38%)
         occurrences all number
    1
    1
    Pulmonary embolism
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Pulmonary fibrosis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Pulmonary oedema
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Respiratory acidosis
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 42 (2.38%)
         occurrences all number
    1
    1
    Respiratory disorder
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Respiratory distress
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Sleep apnoea syndrome
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Stridor
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Psychiatric disorders
    Aggression
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Agitation
         subjects affected / exposed
    2 / 41 (4.88%)
    4 / 42 (9.52%)
         occurrences all number
    2
    4
    Confusional state
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 42 (2.38%)
         occurrences all number
    1
    1
    Anxiety
         subjects affected / exposed
    0 / 41 (0.00%)
    4 / 42 (9.52%)
         occurrences all number
    0
    4
    Delirium
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Depression
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Hallucination, visual
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Insomnia
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 42 (2.38%)
         occurrences all number
    1
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Staphylococcus test positive
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Weight decreased
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Transaminases increased
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Axillary nerve injury
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Endotracheal intubation complication
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Eschar
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 42 (0.00%)
         occurrences all number
    2
    0
    Fall
         subjects affected / exposed
    0 / 41 (0.00%)
    2 / 42 (4.76%)
         occurrences all number
    0
    2
    Toxicity to various agents
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Tracheal haemorrhage
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Arrhythmia
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Bradycardia
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 42 (0.00%)
         occurrences all number
    2
    0
    Atrial fibrillation
         subjects affected / exposed
    3 / 41 (7.32%)
    6 / 42 (14.29%)
         occurrences all number
    3
    6
    Bundle branch block left
         subjects affected / exposed
    0 / 41 (0.00%)
    2 / 42 (4.76%)
         occurrences all number
    0
    2
    Extrasystoles
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Cardiac failure
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Pericardial effusion
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Mitral valve incompetence
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Sinus tachycardia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Supraventricular extrasystoles
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Tachycardia
         subjects affected / exposed
    1 / 41 (2.44%)
    2 / 42 (4.76%)
         occurrences all number
    1
    2
    Nervous system disorders
    Agitation
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Akinesia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Essential tremor
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Facial paralysis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Hepatic encephalopathy
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Intensive care unit acquired weakness
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Memory impairment
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Paraparesis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Partial seizures
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Partial seizures with secondary generalisation
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Presyncope
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Tremor
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    9 / 41 (21.95%)
    8 / 42 (19.05%)
         occurrences all number
    9
    8
    Coagulopathy
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Anaemia macrocytic
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Heparin-induced thrombocytopenia
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Lymphopenia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Leukocytosis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Thrombocytopenia
         subjects affected / exposed
    1 / 41 (2.44%)
    3 / 42 (7.14%)
         occurrences all number
    1
    3
    Normochromic normocytic anaemia
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Thrombocytosis
         subjects affected / exposed
    2 / 41 (4.88%)
    1 / 42 (2.38%)
         occurrences all number
    2
    1
    Thymus disorder
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Ascites
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Abdominal distension
         subjects affected / exposed
    0 / 41 (0.00%)
    4 / 42 (9.52%)
         occurrences all number
    0
    4
    Colitis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Constipation
         subjects affected / exposed
    4 / 41 (9.76%)
    5 / 42 (11.90%)
         occurrences all number
    4
    5
    Colonic pseudo-obstruction
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Diarrhoea
         subjects affected / exposed
    4 / 41 (9.76%)
    5 / 42 (11.90%)
         occurrences all number
    4
    5
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Haematemesis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Impaired gastric emptying
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Loose tooth
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Mouth haemorrhage
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Nausea
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Odynophagia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Oesophagitis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Pancreatitis acute
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Rectal haemorrhage
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Tooth loss
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Toothache
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Vomiting
         subjects affected / exposed
    0 / 41 (0.00%)
    5 / 42 (11.90%)
         occurrences all number
    0
    5
    Hepatobiliary disorders
    Cholestasis
         subjects affected / exposed
    1 / 41 (2.44%)
    5 / 42 (11.90%)
         occurrences all number
    1
    5
    Hepatic cirrhosis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Hepatocellular injury
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 42 (0.00%)
         occurrences all number
    2
    0
    Hepatic failure
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Hepatomegaly
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Hepatorenal syndrome
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Hypertransaminasaemia
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Alopecia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Decubitus ulcer
         subjects affected / exposed
    2 / 41 (4.88%)
    2 / 42 (4.76%)
         occurrences all number
    2
    2
    Erythema
         subjects affected / exposed
    1 / 41 (2.44%)
    3 / 42 (7.14%)
         occurrences all number
    1
    3
    Intertrigo
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Rash
         subjects affected / exposed
    1 / 41 (2.44%)
    2 / 42 (4.76%)
         occurrences all number
    1
    2
    Rash macular
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Skin lesion
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Skin maceration
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Skin reaction
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Skin ulcer
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Subcutaneous emphysema
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Urticaria
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 41 (4.88%)
    1 / 42 (2.38%)
         occurrences all number
    2
    1
    Dysuria
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Chronic kidney disease
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Haematuria
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Neurogenic bladder
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Oliguria
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Renal failure
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Renal impairment
         subjects affected / exposed
    0 / 41 (0.00%)
    2 / 42 (4.76%)
         occurrences all number
    0
    2
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Primary hypothyroidism
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Hyperparathyroidism
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Back pain
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Muscular weakness
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Myopathy
         subjects affected / exposed
    1 / 41 (2.44%)
    2 / 42 (4.76%)
         occurrences all number
    1
    2
    Infections and infestations
    Citrobacter infection
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Empyema
         subjects affected / exposed
    2 / 41 (4.88%)
    1 / 42 (2.38%)
         occurrences all number
    2
    1
    Conjunctivitis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Fungal skin infection
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Genital candidiasis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Herpes virus infection
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Infectious pleural effusion
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Mediastinitis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Influenza
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Oral herpes
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Pneumonia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Pseudomonal sepsis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Pseudomonas infection
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 42 (0.00%)
         occurrences all number
    2
    0
    Rhinitis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Sepsis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Septic shock
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Serratia infection
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Skin candida
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Subcutaneous abscess
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Tracheitis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Urinary tract infection
         subjects affected / exposed
    0 / 41 (0.00%)
    2 / 42 (4.76%)
         occurrences all number
    0
    2
    Urinary tract infection pseudomonal
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Cell death
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Hyperammonaemia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Feeding intolerance
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 42 (2.38%)
         occurrences all number
    1
    1
    Hyperamylasaemia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Hyperglycaemia
         subjects affected / exposed
    1 / 41 (2.44%)
    4 / 42 (9.52%)
         occurrences all number
    1
    4
    Hyperlactacidaemia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Hyperkalaemia
         subjects affected / exposed
    4 / 41 (9.76%)
    2 / 42 (4.76%)
         occurrences all number
    4
    2
    Hypernatraemia
         subjects affected / exposed
    6 / 41 (14.63%)
    1 / 42 (2.38%)
         occurrences all number
    6
    1
    Hyperphosphataemia
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Hypervolaemia
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Hypocalcaemia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 42 (2.38%)
         occurrences all number
    1
    1
    Hypoglycaemia
         subjects affected / exposed
    0 / 41 (0.00%)
    3 / 42 (7.14%)
         occurrences all number
    0
    3
    Hypokalaemia
         subjects affected / exposed
    4 / 41 (9.76%)
    5 / 42 (11.90%)
         occurrences all number
    4
    5
    Hypomagnesaemia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Hyponatraemia
         subjects affected / exposed
    0 / 41 (0.00%)
    3 / 42 (7.14%)
         occurrences all number
    0
    3
    Hypophosphataemia
         subjects affected / exposed
    3 / 41 (7.32%)
    2 / 42 (4.76%)
         occurrences all number
    3
    2
    Metabolic acidosis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    Malnutrition
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    Metabolic alkalosis
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 42 (2.38%)
         occurrences all number
    1
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 Nov 2016
    Protocol Amendment 1: The primary purpose of this amendment is to update the study objectives to explore the long term safety assessment.
    01 Aug 2017
    Protocol Amendment 2: The primary purpose of this amendment is to update the clinical study protocol regarding the reformulation of the placebo.
    28 May 2018
    Protocol Amendment 3: The primary purpose of this amendment is to update the inclusion and exclusion criteria’s.
    19 Dec 2019
    Protocol Amendment 5: The primary purpose of this amendment is to update the enrollment number, Schedule of Study Assessments and the Study Design.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    26 Jun 2017
    Study enrolment was temporarily paused in 2017 in order for the study’s placebo to be reformulated.
    01 Aug 2017

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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