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    Clinical Trial Results:
    A Phase IIa Study of the Safety, Tolerability and Hemodynamic Effects of a Continuous 6-Hour Intravenous Infusion of CXL-1427 in Hospitalized Patients with Systolic Heart Failure

    Summary
    EudraCT number
    		 2014-000771-24
    Trial protocol
    		 DE  
    Global end of trial date
    21 Mar 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    21 Apr 2019
    First version publication date
    21 Apr 2019
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CV013-006
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Other Identifier: CXL-1427-02
    Sponsors
    Sponsor organisation name
    Bristol-Myers Squibb International Corporation
    Sponsor organisation address
    Chaussée de la Hulpe 185, Brussels, Belgium, 1170
    Public contact
    EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, clinical.trials@bms.com
    Scientific contact
    EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, clinical.trials@bms.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    21 Mar 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Mar 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Evaluate the safety and tolerability of 6-hour intravenous infusions of CXL-1427 in patients with systolic congestive heart failure. Evaluate the effects of 6-hour intravenous infusions of CXL-1427 on pulmonary capillary wedge pressure (PCWP), pulmonary artery diastolic pressure (PAD) and cardiac index (CI), as measured by an indwelling pulmonary artery (PA) catheter
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    09 Jul 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 3
    Country: Number of subjects enrolled
    Jordan: 3
    Country: Number of subjects enrolled
    Poland: 6
    Country: Number of subjects enrolled
    Russian Federation: 21
    Country: Number of subjects enrolled
    United States: 37
    Worldwide total number of subjects
    70
    EEA total number of subjects
    9
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    46
    From 65 to 84 years
    24
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 70 participants were enrolled of which only 46 participants received treatment. 24 were not treated due to screen failures, 3 of the 24 were randomized but not dosed due to other reasons.

    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
    		 Investigator, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Subjects received matching placebo intravenous (IV) infusion.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Placebo of BMS-986231
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    5% Dextrose & 10mM potassium acetate as same IV solution diluents used in active

    Arm title
    		 CXL-1427 3μg/kg/min
    Arm description
    		 Subjects received CXL-1427 3 microgram per kilogram per minute (μg/kg/min) IV infusion as 90 milliliter (mL) of dosing solution at a rate of 15 milliliter per hour (mL/hour) for six hours.
    Arm type
    		 Experimental

    Investigational medicinal product name
    CXL-1427
    Investigational medicinal product code
    BMS-986231
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    3 mcg/kg/min

    Arm title
    		 CXL-1427 5μg/kg/min
    Arm description
    		 Subjects received CXL-1427 5 μg/kg/min IV infusion as 90 mL of dosing solution at a rate of 15 mL/hour for six hours.
    Arm type
    		 Experimental

    Investigational medicinal product name
    CXL-1427
    Investigational medicinal product code
    BMS-986231
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    5 mcg/kg/min

    Arm title
    		 CXL-1427 7μg/kg/min
    Arm description
    		 Subjects received CXL-1427 7 μg/kg/min IV infusion as 150 mL of dosing solution at a rate of 25 mL/hour for six hours.
    Arm type
    		 Experimental

    Investigational medicinal product name
    CXL-1427
    Investigational medicinal product code
    BMS-986231
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    7 mcg/kg/min

    Arm title
    		 CXL-1427 12μg/kg/min
    Arm description
    		 Subjects received CXL-1427 12 μg/kg/min IV infusion as 180 mL of dosing solution at a rate of 30 mL/hour for six hours.
    Arm type
    		 Experimental

    Investigational medicinal product name
    CXL-1427
    Investigational medicinal product code
    BMS-986231
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    12 mcg/kg/min

    Number of subjects in period 1 [1]
    		Placebo CXL-1427 3μg/kg/min CXL-1427 5μg/kg/min CXL-1427 7μg/kg/min CXL-1427 12μg/kg/min
    Started
    12
    6
    9
    12
    7
    Completed
    12
    5
    8
    12
    7
    Not completed
    0
    1
    1
    0
    0
         Adverse event, non-fatal
    -
    1
    -
    -
    -
         Lost to follow-up
    -
    -
    1
    -
    -
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: 70 participants were enrolled worldwide, of which only 46 participants received treatment. Baseline period subject disposition is shown for 46 randomized and treated participants

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received matching placebo intravenous (IV) infusion.

    Reporting group title
    CXL-1427 3μg/kg/min
    Reporting group description
    		 Subjects received CXL-1427 3 microgram per kilogram per minute (μg/kg/min) IV infusion as 90 milliliter (mL) of dosing solution at a rate of 15 milliliter per hour (mL/hour) for six hours.

    Reporting group title
    CXL-1427 5μg/kg/min
    Reporting group description
    		 Subjects received CXL-1427 5 μg/kg/min IV infusion as 90 mL of dosing solution at a rate of 15 mL/hour for six hours.

    Reporting group title
    CXL-1427 7μg/kg/min
    Reporting group description
    		 Subjects received CXL-1427 7 μg/kg/min IV infusion as 150 mL of dosing solution at a rate of 25 mL/hour for six hours.

    Reporting group title
    CXL-1427 12μg/kg/min
    Reporting group description
    		 Subjects received CXL-1427 12 μg/kg/min IV infusion as 180 mL of dosing solution at a rate of 30 mL/hour for six hours.

    Reporting group values
    		 Placebo CXL-1427 3μg/kg/min CXL-1427 5μg/kg/min CXL-1427 7μg/kg/min CXL-1427 12μg/kg/min Total
    Number of subjects
    		 12 6 9 12 7 46
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0
        Adults (18-64 years)
    		 9 3 6 8 6 32
        From 65-84 years
    		 3 3 3 4 1 14
        85 years and over
    		 0 0 0 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 62.7 ( 9.25 ) 63.5 ( 3.51 ) 61.1 ( 11.36 ) 61.6 ( 10.26 ) 48.3 ( 17.49 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 2 2 1 0 2 7
        Male
    		 10 4 8 12 5 39

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received matching placebo intravenous (IV) infusion.

    Reporting group title
    CXL-1427 3μg/kg/min
    Reporting group description
    		 Subjects received CXL-1427 3 microgram per kilogram per minute (μg/kg/min) IV infusion as 90 milliliter (mL) of dosing solution at a rate of 15 milliliter per hour (mL/hour) for six hours.

    Reporting group title
    CXL-1427 5μg/kg/min
    Reporting group description
    		 Subjects received CXL-1427 5 μg/kg/min IV infusion as 90 mL of dosing solution at a rate of 15 mL/hour for six hours.

    Reporting group title
    CXL-1427 7μg/kg/min
    Reporting group description
    		 Subjects received CXL-1427 7 μg/kg/min IV infusion as 150 mL of dosing solution at a rate of 25 mL/hour for six hours.

    Reporting group title
    CXL-1427 12μg/kg/min
    Reporting group description
    		 Subjects received CXL-1427 12 μg/kg/min IV infusion as 180 mL of dosing solution at a rate of 30 mL/hour for six hours.

    Primary: Number of Participants with Treatment-Emergent Adverse Events

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    End point title
    		 Number of Participants with Treatment-Emergent Adverse Events [1]
    End point description
    A treatment-emergent adverse event (TEAE) was defined as an AE with onset after the start of the study drug infusion at Hour 00:00 through 30 days after the stop of the study drug infusion. All TEAEs and pertinent subsets of TEAEs (e.g., TEAEs with onset during the infusion of study drug, serious TEAEs, etc.) were summarized by system organ class (SOC), preferred term (PT) and treatment group
    End point type
    Primary
    End point timeframe
    30 days following the initiation of treatment
    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 summary statistics were planned for this endpoint
    End point values
    		 Placebo CXL-1427 3μg/kg/min CXL-1427 5μg/kg/min CXL-1427 7μg/kg/min CXL-1427 12μg/kg/min
    Number of subjects analysed
    12
    6
    9
    12
    7
    Units: Participants
        At least one TEAE
    3
    5
    5
    7
    3
        At least one Severe TEAE
    0
    4
    0
    2
    1
        At least one Drug-related severe TEAE
    0
    0
    0
    0
    0
        At least one Serious TEAE
    1
    3
    1
    3
    1
        At least one Drug-related serious TEAE
    0
    0
    0
    0
    0
        At least one Fatal TEAE
    0
    1
    0
    0
    0
        At least one Drug-related fatal TEAE
    0
    0
    0
    0
    0
        At least one TEAE leading to drug interruption
    0
    0
    0
    0
    0
        At least one TEAE leading to drug discontinuation
    0
    0
    0
    0
    1
    No statistical analyses for this end point

    Primary: Mean Time Averaged Change from Baseline in Adjudicated Pulmonary Capillary Wedge Pressure (PCWP) During Infusion

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    End point title
    		 Mean Time Averaged Change from Baseline in Adjudicated Pulmonary Capillary Wedge Pressure (PCWP) During Infusion
    End point description
    The effect of CXL-1427 on PCWP is presented as the mean time-averaged change from baseline over the course of infusion of CXL-1427 or placebo in adjudicated pulmonary capillary wedge pressure (PCWP) on a modified intent-to-treat population
    End point type
    Primary
    End point timeframe
    Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion
    End point values
    		 Placebo CXL-1427 3μg/kg/min CXL-1427 5μg/kg/min CXL-1427 7μg/kg/min CXL-1427 12μg/kg/min
    Number of subjects analysed
    12
    6
    9
    12
    7
    Units: mm Hg
        arithmetic mean (standard deviation)
    -0.17 ( 2.35 )
    -3.00 ( 3.06 )
    -5.06 ( 3.93 )
    -4.42 ( 4.00 )
    -4.75 ( 3.50 )
    Statistical analysis title
    		 PCWP : CXL-1427 3ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 3μg/kg/min
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0059
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 PWCP: CXL-1427 5ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 5μg/kg/min
    Number of subjects included in analysis
    21
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0001
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 PWCP: CXL-1427 7ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 7μg/kg/min
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0062
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 PWCP: CXL-1427 12ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 12μg/kg/min
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0086
    Method
    		 Mixed models analysis
    Confidence interval

    Primary: Mean Time-Averaged Change from Baseline in Adjudicated Pulmonary artery diastolic pressure (PAD) During the Infusion

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    End point title
    		 Mean Time-Averaged Change from Baseline in Adjudicated Pulmonary artery diastolic pressure (PAD) During the Infusion
    End point description
    Pulmonary artery diastolic pressure (PAD) was measured by an indwelling PA catheter. Pulmonary artery diastolic pressure (PAD) approximates pulmonary capillary wedge pressure in normal individuals. The effects of CXL-1427 on time-averaged PAD during the course of the infusion are presented.
    End point type
    Primary
    End point timeframe
    Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation
    End point values
    		 Placebo CXL-1427 3μg/kg/min CXL-1427 5μg/kg/min CXL-1427 7μg/kg/min CXL-1427 12μg/kg/min
    Number of subjects analysed
    12
    6
    9
    12
    7
    Units: mm Hg
        arithmetic mean (standard deviation)
    -0.21 ( 3.35 )
    -3.69 ( 2.55 )
    -4.17 ( 4.02 )
    -2.67 ( 3.63 )
    -3.17 ( 1.82 )
    Statistical analysis title
    		 PAD: CXL-1427 3ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 3μg/kg/min
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0076
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 PAD: CXL-1427 5ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 5μg/kg/min
    Number of subjects included in analysis
    21
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0052
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 PAD: CXL-1427 7ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 7μg/kg/min
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1064
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 PAD: CXL-1427 12ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 12μg/kg/min
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1151
    Method
    		 Mixed models analysis
    Confidence interval

    Primary: Mean Time-Averaged Percent Change from Baseline in Cardiac Index (Fick)

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    End point title
    		 Mean Time-Averaged Percent Change from Baseline in Cardiac Index (Fick)
    End point description
    Cardiac index is a measure of cardiac function, relating the cardiac output from the left ventricle in one minute to body surface area. It is calculated using the Fick principle, using oxygen consumption measured with a metabolic cart, hemoglobin levels, and the difference between arterial and superior vena cava oxygen saturation measured by co-oximetry. Cardiac index as calculated by the Fick method was performed using an assumed oxygen consumption value of 125 ml/min per m2 of body surface area. i.e., an assumed Fick method.
    End point type
    Primary
    End point timeframe
    Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation
    End point values
    		 Placebo CXL-1427 3μg/kg/min CXL-1427 5μg/kg/min CXL-1427 7μg/kg/min CXL-1427 12μg/kg/min
    Number of subjects analysed
    12
    6
    9
    12
    7
    Units: Percentage
        arithmetic mean (standard deviation)
    7.95 ( 16.15 )
    0.53 ( 18.12 )
    13.41 ( 23.53 )
    9.59 ( 11.91 )
    -9.58 ( 18.02 )
    Statistical analysis title
    		 CI (Fick): CXL-1427 3ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 3μg/kg/min
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4241
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 CI (Fick): CXL-1427 5ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 5μg/kg/min
    Number of subjects included in analysis
    21
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4035
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 CI (Fick): CXL-1427 7ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 7μg/kg/min
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.8308
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 CI (Fick): CXL-1427 12ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 12μg/kg/min
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.118
    Method
    		 Mixed models analysis
    Confidence interval

    Secondary: Mean Time-Averaged Change from Baseline in Adjudicated Pulmonary Artery Systolic Pressure (PAS) During the Infusion

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    End point title
    		 Mean Time-Averaged Change from Baseline in Adjudicated Pulmonary Artery Systolic Pressure (PAS) During the Infusion
    End point description
    Pulmonary artery systolic pressure (PAS) was measured by an indwelling PA catheter. The effects of CXL-1427 on time-averaged PAS during the course of the infusion are presented
    End point type
    Secondary
    End point timeframe
    Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation
    End point values
    		 Placebo CXL-1427 3μg/kg/min CXL-1427 5μg/kg/min CXL-1427 7μg/kg/min CXL-1427 12μg/kg/min
    Number of subjects analysed
    12
    6
    9
    12
    7
    Units: mm Hg
        arithmetic mean (standard deviation)
    -0.73 ( 3.73 )
    -6.42 ( 2.59 )
    -5.98 ( 5.31 )
    -6.26 ( 5.09 )
    -4.24 ( 5.24 )
    Statistical analysis title
    		 PAS: CXL-1427 3ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 3μg/kg/min
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0048
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 PAS: CXL-1427 5ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 5μg/kg/min
    Number of subjects included in analysis
    21
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0022
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 PAS: CXL-1427 7ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 7μg/kg/min
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0045
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 PAS: CXL-1427 12ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 12μg/kg/min
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0294
    Method
    		 Mixed models analysis
    Confidence interval

    Secondary: Mean Time-Averaged Change from Baseline in Adjudicated Right Atrial Pressure (RAP) During the Infusion

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    End point title
    		 Mean Time-Averaged Change from Baseline in Adjudicated Right Atrial Pressure (RAP) During the Infusion
    End point description
    The effects of CXL-1427 on time-averaged RAP during the course of the infusion are presented
    End point type
    Secondary
    End point timeframe
    Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation
    End point values
    		 Placebo CXL-1427 3μg/kg/min CXL-1427 5μg/kg/min CXL-1427 7μg/kg/min CXL-1427 12μg/kg/min
    Number of subjects analysed
    12
    6
    9
    12
    7
    Units: mm Hg
        arithmetic mean (standard deviation)
    -0.03 ( 2.61 )
    -1.92 ( 2.91 )
    -2.08 ( 3.10 )
    -2.17 ( 2.42 )
    -4.60 ( 3.23 )
    Statistical analysis title
    		 RAP: CXL-1427 3ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 3μg/kg/min
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2022
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 RAP: CXL-1427 5ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 5μg/kg/min
    Number of subjects included in analysis
    21
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0658
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 RAP: CXL-1427 7ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 7μg/kg/min
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0741
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 RAP: CXL-1427 12ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 12μg/kg/min
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0497
    Method
    		 Mixed models analysis
    Confidence interval

    Secondary: Mean Time-Averaged Change from Baseline in Mean Arterial Blood Pressure (MAP) During the Infusion

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    End point title
    		 Mean Time-Averaged Change from Baseline in Mean Arterial Blood Pressure (MAP) During the Infusion
    End point description
    Mean arterial pressure during infusion of CXL-1427 or placebo on a modified intent-to-treat population is presented
    End point type
    Secondary
    End point timeframe
    Baseline, Hour 24 after infusion, Follow-up visit 1
    End point values
    		 Placebo CXL-1427 3μg/kg/min CXL-1427 5μg/kg/min CXL-1427 7μg/kg/min CXL-1427 12μg/kg/min
    Number of subjects analysed
    12
    6
    9
    12
    7
    Units: mm Hg
        arithmetic mean (standard deviation)
    -1.11 ( 5.01 )
    -5.84 ( 4.46 )
    -4.75 ( 10.93 )
    -7.16 ( 7.67 )
    -6.69 ( 5.67 )
    Statistical analysis title
    		 MAP: CXL-1427 3ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 3μg/kg/min
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1842
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 MAP: CXL-1427 5ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 5μg/kg/min
    Number of subjects included in analysis
    21
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3328
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 MAP: CXL-1427 7ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 7μg/kg/min
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1465
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 MAP: CXL-1427 12ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 12μg/kg/min
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2799
    Method
    		 Mixed models analysis
    Confidence interval

    Secondary: Mean Time-Averaged Change from Baseline in Systolic Blood Pressure (SBP) During the Infusion

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    End point title
    		 Mean Time-Averaged Change from Baseline in Systolic Blood Pressure (SBP) During the Infusion
    End point description
    Mean Time-Averaged Change from Baseline in Systolic Blood Pressure during infusion of CXL-1427 or placebo on a modified intent-to-treat population is presented
    End point type
    Secondary
    End point timeframe
    Baseline, Hour 24 after infusion, Follow-up visit 1
    End point values
    		 Placebo CXL-1427 3μg/kg/min CXL-1427 5μg/kg/min CXL-1427 7μg/kg/min CXL-1427 12μg/kg/min
    Number of subjects analysed
    12
    6
    9
    12
    7
    Units: mm Hg
        arithmetic mean (standard deviation)
    -3.15 ( 5.53 )
    -8.69 ( 4.43 )
    -2.41 ( 12.57 )
    -6.81 ( 9.54 )
    -4.64 ( 4.04 )
    Statistical analysis title
    		 SBP: CXL-1427 3ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 3μg/kg/min
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2499
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 SBP: CXL-1427 5ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 5μg/kg/min
    Number of subjects included in analysis
    21
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.8281
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 SBP: CXL-1427 7ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 7μg/kg/min
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4121
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 SBP: CXL-1427 12ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 12μg/kg/min
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.8592
    Method
    		 Mixed models analysis
    Confidence interval

    Secondary: Mean Time-Averaged Change from Baseline in Diastolic Blood Pressure (DBP) During the Infusion

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    End point title
    		 Mean Time-Averaged Change from Baseline in Diastolic Blood Pressure (DBP) During the Infusion
    End point description
    Mean Time-Averaged Change from Baseline in Diastolic Blood Pressure during infusion of CXL-1427 or placebo on a modified intent-to-treat population is presented
    End point type
    Secondary
    End point timeframe
    Baseline, Hour 24 after infusion, Follow-up visit 1
    End point values
    		 Placebo CXL-1427 3μg/kg/min CXL-1427 5μg/kg/min CXL-1427 7μg/kg/min CXL-1427 12μg/kg/min
    Number of subjects analysed
    12
    6
    9
    12
    7
    Units: mm Hg
        arithmetic mean (standard deviation)
    -0.09 ( 8.30 )
    -4.42 ( 5.22 )
    -5.93 ( 11.07 )
    -7.33 ( 8.51 )
    -7.71 ( 8.03 )
    Statistical analysis title
    		 DBP: CXL-1427 3ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 3μg/kg/min
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1391
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 DBP : CXL-1427 5ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 5μg/kg/min
    Number of subjects included in analysis
    21
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1724
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 DBP: CXL-1427 7ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 7μg/kg/min
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1245
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 DBP: CXL-1427 12ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 12μg/kg/min
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.169
    Method
    		 Mixed models analysis
    Confidence interval

    Secondary: Mean Time-Averaged Change from Baseline in Heart Rate (HR) During the Infusion

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    End point title
    		 Mean Time-Averaged Change from Baseline in Heart Rate (HR) During the Infusion
    End point description
    Mean Time-Averaged Change from Baseline in Heart Rate during infusion of CXL-1427 or placebo on a modified intent-to-treat population is presented
    End point type
    Secondary
    End point timeframe
    Baseline, Hour 24 after infusion, Follow-up visit 1
    End point values
    		 Placebo CXL-1427 3μg/kg/min CXL-1427 5μg/kg/min CXL-1427 7μg/kg/min CXL-1427 12μg/kg/min
    Number of subjects analysed
    12
    6
    9
    12
    7
    Units: Beats/min
        arithmetic mean (standard deviation)
    -0.79 ( 6.34 )
    1.06 ( 3.74 )
    -3.09 ( 6.84 )
    1.00 ( 7.08 )
    -4.52 ( 16.92 )
    Statistical analysis title
    		 HR: CXL-1427 3ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 3μg/kg/min
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4936
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 HR: CXL-1427 5ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 5μg/kg/min
    Number of subjects included in analysis
    21
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.992
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 HR: CXL-1427 7ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 7μg/kg/min
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2789
    Method
    		 Mixed models analysis
    Confidence interval
    Statistical analysis title
    		 HR: CXL-1427 12ug/kg/min vs Placebo
    Comparison groups
    Placebo v CXL-1427 12μg/kg/min
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.91
    Method
    		 Mixed models analysis
    Confidence interval

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received matching placebo intravenous (IV) infusion.

    Reporting group title
    CXL-1427 3 μg/kg/min
    Reporting group description
    		 Subjects received CXL-1427 3 microgram per kilogram per minute (μg/kg/min) IV infusion as 90 milliliter (mL) of dosing solution at a rate of 15 milliliter per hour (mL/hour) for six hours.

    Reporting group title
    CXL-1427 5 μg/kg/min
    Reporting group description
    		 Subjects received CXL-1427 5 μg/kg/min IV infusion as 90 mL of dosing solution at a rate of 15 mL/hour for six hours.

    Reporting group title
    CXL-1427 7 μg/kg/min
    Reporting group description
    		 Subjects received CXL-1427 7 μg/kg/min IV infusion as 150 mL of dosing solution at a rate of 25 mL/hour for six hours.

    Reporting group title
    CXL-1427 12 μg/kg/min
    Reporting group description
    		 Subjects received CXL-1427 12 μg/kg/min IV infusion as 180 mL of dosing solution at a rate of 30 mL/hour for six hours.

    Serious adverse events
    		 Placebo CXL-1427 3 μg/kg/min CXL-1427 5 μg/kg/min CXL-1427 7 μg/kg/min CXL-1427 12 μg/kg/min
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 12 (8.33%)
    3 / 6 (50.00%)
    1 / 9 (11.11%)
    3 / 12 (25.00%)
    1 / 7 (14.29%)
         number of deaths (all causes)
    0
    1
    0
    0
    0
         number of deaths resulting from adverse events
    0
    1
    0
    0
    0
    Cardiac disorders
    Atrial flutter
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block complete
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory failure
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Toxic epidermal necrolysis
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal failure
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Rhinovirus infection
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
    alternative assessment type: Non-systematic
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo CXL-1427 3 μg/kg/min CXL-1427 5 μg/kg/min CXL-1427 7 μg/kg/min CXL-1427 12 μg/kg/min
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 12 (25.00%)
    6 / 6 (100.00%)
    6 / 9 (66.67%)
    7 / 12 (58.33%)
    4 / 7 (57.14%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Benign neoplasm of thyroid gland
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Vascular disorders
    Hypotension
    alternative assessment type: Non-systematic
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    3 / 9 (33.33%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    3
    0
    1
    General disorders and administration site conditions
    Catheter site haemorrhage
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Chest pain
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Respiratory failure
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Psychiatric disorders
    Psychotic disorder
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Investigations
    Blood creatinine increased
    alternative assessment type: Non-systematic
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Vascular pseudoaneurysm
    alternative assessment type: Non-systematic
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Cardiac disorders
    Atrial flutter
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Atrioventricular block complete
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    0
    0
    0
    1
    Cardiac failure
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Cardiac failure congestive
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    Cardiorenal syndrome
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Low cardiac output syndrome
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    0
    0
    0
    1
    Tachycardia
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Ventricular tachycardia
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Nervous system disorders
    Dizziness
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Headache
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    2 / 12 (16.67%)
    1 / 7 (14.29%)
         occurrences all number
    0
    0
    0
    2
    1
    Syncope
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    0
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Ecchymosis
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Toxic epidermal necrolysis
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Renal and urinary disorders
    Renal failure
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Infections and infestations
    Rhinovirus infection
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Urinary tract infection
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Metabolism and nutrition disorders
    Dehydration
    alternative assessment type: Non-systematic
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Hypoglycaemia
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

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