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    Clinical Trial Results:
    A Phase II, randomised, double blind, placebo controlled, seven way crossover study to assess the effect of single doses of RPL554 compared to salbutamol and placebo administered by nebuliser on lung function of patients with chronic asthma

    Summary
    EudraCT number
    		 2014-005615-17
    Trial protocol
    		 GB   SE  
    Global end of trial date
    17 Nov 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    25 Oct 2017
    First version publication date
    25 Oct 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    RPL554-008-2014
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02427165
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Verona Pharma plc
    Sponsor organisation address
    3 More London Riverside, London, United Kingdom, SE1 2RE
    Public contact
    Kenneth Newman, Verona Pharma plc, +44 203 283 4200, ken.newman@veronapharma.com
    Scientific contact
    Kenneth Newman, Verona Pharma plc, +44 203 283 4200, ken.newman@veronapharma.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
    02 Mar 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    17 Nov 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Nov 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To investigate the bronchodilator effect of single doses of RPL554 administered by nebuliser on peak and average* FEV1 over 12 hours compared with placebo and salbutamol. *The average effect was calculated as the area under the curve divided by the length of the time interval of interest, and the peak effect as the minimum value for diastolic blood pressure or maximum value for other variables
    Protection of trial subjects
    Standard procedures for emergency care were followed for any individual adverse events if clinically needed. Short acting bronchodilators could be used as rescue medication.
    Background therapy
    		 Salbutamol was used as rescue medication
    Evidence for comparator
    		 Two different single doses (2.5 mg and 7.5 mg) of nebulised salbutamol were included; 2.5 mg is the standard dose of salbutamol and was intended as a benchmark for bronchodilation, 7.5 mg is dose which may be used in acute asthma and was intended to show the maximum bronchodilation achievable using salbutamol
    Actual start date of recruitment
    13 May 2015
    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
    Sweden: 20
    Country: Number of subjects enrolled
    United Kingdom: 9
    Worldwide total number of subjects
    29
    EEA total number of subjects
    29
    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)
    29
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Recruitment was started on 13 May 2015 in the UK and 25 May 2015 in Sweden. Overall, 153 patients were screened for the study and 29 were treated . Patients received study treatment between 21 May 2015 and 15 November 2015. A total of 25 patients completed the study and four were withdrawn

    Pre-assignment
    Screening details
    		 153 patients were screened (128 in the UK and 25 in Sweden). The main reasons for screen failure were reversibility test criteria not met (50 patients), BMI out of range or vital signs out of range (13 patients each). Patients had to discontinue LABAs and LAMAs for 72 hours and SABAs and SAMAs for 8 hours before screening

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

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 0.4 mg RPL554
    Arm description
    		 Single dose of 0.4 mg RPL554 administered using a nebuliser
    Arm type
    		 Experimental

    Investigational medicinal product name
    RPL554
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nebuliser suspension
    Routes of administration
    Inhalation use
    Dosage and administration details
    Single dose of 0.4 mg RPL554 diluted to a 5 mL volume administered using a nebuliser.

    Arm title
    		 1.5 mg RPL554
    Arm description
    		 Single dose of 1.5 mg RPL554 administered using a nebuliser
    Arm type
    		 Experimental

    Investigational medicinal product name
    RPL554
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nebuliser suspension
    Routes of administration
    Inhalation use
    Dosage and administration details
    Single dose of 1.5 mg RPL554 diluted to a 5 mL volume administered using a nebuliser.

    Arm title
    		 6 mg RPL554
    Arm description
    		 Single dose of 6 mg RPL554 administered using a nebuliser
    Arm type
    		 Experimental

    Investigational medicinal product name
    RPL554
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nebuliser suspension
    Routes of administration
    Inhalation use
    Dosage and administration details
    Single dose of 6 mg RPL554 diluted to a 5 mL volume administered using a nebuliser.

    Arm title
    		 24 mg RPL554
    Arm description
    		 Single dose of 24 mg RPL554 administered using a nebuliser
    Arm type
    		 Experimental

    Investigational medicinal product name
    RPL554
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nebuliser suspension
    Routes of administration
    Inhalation use
    Dosage and administration details
    Single dose of 24 mg RPL554 diluted to a 5 mL volume administered using a nebuliser.

    Arm title
    		 Placebo
    Arm description
    		 Single dose of placebo administered using a nebuliser
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nebuliser suspension
    Routes of administration
    Inhalation use
    Dosage and administration details
    Single dose of placebo as a 5 mL volume administered using a nebuliser.

    Arm title
    		 2.5 mg salbutamol
    Arm description
    		 Single dose of 2.5 mg salbutamol administered using a nebuliser
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Salbutamol
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nebuliser solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Single dose of 2.5 mg salbutamol diluted to a 5 mL volume administered using a nebuliser.

    Arm title
    		 7.5 mg salbutamol
    Arm description
    		 Single dose of 7.5 mg salbutamol administered using a nebuliser
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Salbutamol
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nebuliser solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Single dose of 7.5 mg RPL554 administered as a 5 mL volume using a nebuliser.

    Number of subjects in period 1
    		0.4 mg RPL554 1.5 mg RPL554 6 mg RPL554 24 mg RPL554 Placebo 2.5 mg salbutamol 7.5 mg salbutamol
    Started
    26
    27
    26
    27
    26
    28
    28
    Completed
    26
    27
    26
    27
    26
    26
    26
    Not completed
    0
    0
    0
    0
    0
    2
    2
         Physician decision
    -
    -
    -
    -
    -
    -
    1
         Pre-dose FEV1 not comparable with baseline
    -
    -
    -
    -
    -
    2
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Overall Trial
    Reporting group description
    		 -

    Reporting group values
    		 Overall Trial Total
    Number of subjects
    		 29 29
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 29 29
        From 65-84 years
    		 0 0
        85 years and over
    		 0 0
    Age continuous
    Units: years
        arithmetic mean (full range (min-max))
    		 37.6 (21 to 62) -
    Gender categorical
    Units: Subjects
        Female
    		 3 3
        Male
    		 26 26

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    0.4 mg RPL554
    Reporting group description
    		 Single dose of 0.4 mg RPL554 administered using a nebuliser

    Reporting group title
    1.5 mg RPL554
    Reporting group description
    		 Single dose of 1.5 mg RPL554 administered using a nebuliser

    Reporting group title
    6 mg RPL554
    Reporting group description
    		 Single dose of 6 mg RPL554 administered using a nebuliser

    Reporting group title
    24 mg RPL554
    Reporting group description
    		 Single dose of 24 mg RPL554 administered using a nebuliser

    Reporting group title
    Placebo
    Reporting group description
    		 Single dose of placebo administered using a nebuliser

    Reporting group title
    2.5 mg salbutamol
    Reporting group description
    		 Single dose of 2.5 mg salbutamol administered using a nebuliser

    Reporting group title
    7.5 mg salbutamol
    Reporting group description
    		 Single dose of 7.5 mg salbutamol administered using a nebuliser

    Primary: Peak FEV1

    		 Close Top of page
    End point title
    		 Peak FEV1
    End point description
    End point type
    Primary
    End point timeframe
    pre-dose (-30 and -15 minutes), 10, 20, 30, 60, 90 minutes and 2, 4, 6, 8 and 12 hours post-dose
    End point values
    		 0.4 mg RPL554 1.5 mg RPL554 6 mg RPL554 24 mg RPL554 Placebo 2.5 mg salbutamol 7.5 mg salbutamol
    Number of subjects analysed
    26
    27
    26
    27
    26
    28
    28
    Units: Litres
        arithmetic mean (full range (min-max))
    3.432 (1.86 to 4.57)
    3.547 (1.93 to 4.93)
    3.554 (2.03 to 4.89)
    3.749 (2.02 to 5.59)
    3.164 (1.77 to 4.29)
    3.738 (2.05 to 5.26)
    3.748 (2.08 to 5.3)
    Statistical analysis title
    		 Peak FEV1 0.4 mg RPL554 versus placebo
    Comparison groups
    0.4 mg RPL554 v Placebo
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Ratio
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 106.01
         upper limit
    		 111.13
    Statistical analysis title
    		 Peak FEV1 1.5 mg RPL554 versus placebo
    Comparison groups
    Placebo v 1.5 mg RPL554
    Number of subjects included in analysis
    53
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Ratio
    Point estimate
    110.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 107.76
         upper limit
    		 112.97
    Statistical analysis title
    		 Peak FEV1 6 mg RPL554 versus placebo
    Comparison groups
    Placebo v 6 mg RPL554
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Ratio
    Point estimate
    111.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 108.87
         upper limit
    		 114.13
    Statistical analysis title
    		 Peak FEV1 24 mg RPL554 versus placebo
    Comparison groups
    Placebo v 24 mg RPL554
    Number of subjects included in analysis
    53
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Ratio
    Point estimate
    115.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 112.42
         upper limit
    		 117.86
    Statistical analysis title
    		 Peak FEV1 2.5 mg salbutamol versus placebo
    Comparison groups
    Placebo v 2.5 mg salbutamol
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Ratio
    Point estimate
    115.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 113.16
         upper limit
    		 118.59
    Statistical analysis title
    		 Peak FEV1 7.5 mg salbutamol versus placebo
    Comparison groups
    Placebo v 7.5 mg salbutamol
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Ratio
    Point estimate
    117.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 114.9
         upper limit
    		 120.36
    Statistical analysis title
    		 Peak FEV1 24 mg RPL554 versus 2.5 mg salbutamol
    Comparison groups
    2.5 mg salbutamol v 24 mg RPL554
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.59
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Ratio
    Point estimate
    99.37
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 97.1
         upper limit
    		 101.69
    Statistical analysis title
    		 Peak FEV1 24 mg RPL554 versus 7.5 mg salbutamol
    Comparison groups
    7.5 mg salbutamol v 24 mg RPL554
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0702
    Method
    		 ANCOVA
    Parameter type
    		 LS Means Ratio
    Point estimate
    97.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 95.64
         upper limit
    		 100.18

    Primary: Average FEV1

    		 Close Top of page
    End point title
    		 Average FEV1
    End point description
    End point type
    Primary
    End point timeframe
    pre dose (-30 minutes and -15 minutes) and 10 minutes, 20 minutes, 30 minutes, 60 minutes, 90 minutes, 2 hours, 4 hours, 6 hours, 8 hours and 12 hours
    End point values
    		 0.4 mg RPL554 1.5 mg RPL554 6 mg RPL554 24 mg RPL554 Placebo 2.5 mg salbutamol 7.5 mg salbutamol
    Number of subjects analysed
    26
    27
    26
    27
    26
    28
    28
    Units: Litres
        arithmetic mean (full range (min-max))
    3.189 (1.78 to 4.33)
    3.284 (1.85 to 4.6)
    3.318 (1.88 to 4.63)
    3.492 (1.9 to 5.11)
    2.986 (1.7 to 4.22)
    3.375 (1.81 to 4.82)
    3.443 (1.92 to 4.95)
    Statistical analysis title
    		 Average FEV1 0.4 mg RPL554 versus placebo
    Comparison groups
    0.4 mg RPL554 v Placebo
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 Geometric LS Means ratio
    Point estimate
    106.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 104.09
         upper limit
    		 109.34
    Statistical analysis title
    		 Average FEV1 1.5 mg RPL554 versus placebo
    Comparison groups
    Placebo v 1.5 mg RPL554
    Number of subjects included in analysis
    53
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 Geometric LS Means ratio
    Point estimate
    107.64
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 105.03
         upper limit
    		 110.32
    Statistical analysis title
    		 Average FEV1 6 mg RPL554 versus placebo
    Comparison groups
    Placebo v 6 mg RPL554
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 Geometric LS Means ratio
    Point estimate
    109.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 107.07
         upper limit
    		 112.47
    Statistical analysis title
    		 Average FEV1 24 mg RPL554 versus placebo
    Comparison groups
    Placebo v 24 mg RPL554
    Number of subjects included in analysis
    53
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 Geometric LS Means ratio
    Point estimate
    113.41
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 110.65
         upper limit
    		 116.24
    Statistical analysis title
    		 Average FEV1 2.5 mg salbutamol versus placebo
    Comparison groups
    Placebo v 2.5 mg salbutamol
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 Geometric LS Means ratio
    Point estimate
    111.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 108.46
         upper limit
    		 113.88
    Statistical analysis title
    		 Average FEV1 7.5 mg salbutamol versus p...
    Comparison groups
    Placebo v 7.5 mg salbutamol
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 Geometric LS Means ratio
    Point estimate
    114.22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 111.48
         upper limit
    		 117.02
    Statistical analysis title
    		 Average FEV1 6mg RPL554 versus 2.5 mg salbutamol
    Comparison groups
    2.5 mg salbutamol v 6 mg RPL554
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.3042
    Method
    		 ANCOVA
    Parameter type
    		 Geometric LS Means ratio
    Point estimate
    98.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 96.36
         upper limit
    		 101.17
    Statistical analysis title
    		 Average FEV1 24mg RPL554 versus 7.5 mg s...
    Comparison groups
    24 mg RPL554 v 7.5 mg salbutamol
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.5607
    Method
    		 ANCOVA
    Parameter type
    		 Geometric LS Means ratio
    Point estimate
    99.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 96.92
         upper limit
    		 101.72

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From informed consent to end of study visit
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    0.4 mg RPL554
    Reporting group description
    		 Single dose of 0.4 mg RPL554 administed using a nebuliser

    Reporting group title
    1.5 mg RPL554
    Reporting group description
    		 Single dose of 1.5 mg RPL554 administered using a nebuliser

    Reporting group title
    6 mg RPL554
    Reporting group description
    		 Single dose of 6 mg RPL554 administered using a nebuliser

    Reporting group title
    24 mg RPL554
    Reporting group description
    		 Single dose of 24 mg RPL554 administered using a nebuliser

    Reporting group title
    Placebo
    Reporting group description
    		 Single dose of placebo administered using a nebuliser

    Reporting group title
    2.5 mg salbutamol
    Reporting group description
    		 Single dose of 2.5 mg salbutamol administered using a nebuliser

    Reporting group title
    7.5 mg salbutamol
    Reporting group description
    		 Single dose of 7.5 mg salbutamol administered using a nebuliser

    Serious adverse events
    		 0.4 mg RPL554 1.5 mg RPL554 6 mg RPL554 24 mg RPL554 Placebo 2.5 mg salbutamol 7.5 mg salbutamol
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
    0 / 28 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 0.4 mg RPL554 1.5 mg RPL554 6 mg RPL554 24 mg RPL554 Placebo 2.5 mg salbutamol 7.5 mg salbutamol
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    12 / 26 (46.15%)
    9 / 27 (33.33%)
    10 / 26 (38.46%)
    10 / 27 (37.04%)
    5 / 26 (19.23%)
    10 / 28 (35.71%)
    16 / 28 (57.14%)
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    1 / 27 (3.70%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
    7 / 28 (25.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    7
    Tachycardia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    1 / 27 (3.70%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
    3 / 28 (10.71%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    3
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 27 (3.70%)
    1 / 26 (3.85%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    2
    Headache
         subjects affected / exposed
    6 / 26 (23.08%)
    4 / 27 (14.81%)
    3 / 26 (11.54%)
    7 / 27 (25.93%)
    1 / 26 (3.85%)
    0 / 28 (0.00%)
    5 / 28 (17.86%)
         occurrences all number
    6
    4
    3
    8
    1
    0
    5
    Tremor
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 27 (3.70%)
    1 / 26 (3.85%)
    0 / 27 (0.00%)
    1 / 26 (3.85%)
    9 / 28 (32.14%)
    12 / 28 (42.86%)
         occurrences all number
    0
    1
    1
    0
    1
    9
    12
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 27 (0.00%)
    2 / 26 (7.69%)
    1 / 27 (3.70%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
    1 / 28 (3.57%)
         occurrences all number
    1
    0
    2
    1
    0
    0
    1
    Throat irritation
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 27 (7.41%)
    0 / 26 (0.00%)
    0 / 27 (0.00%)
    1 / 26 (3.85%)
    0 / 28 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    2
    0
    0
    1
    0
    0
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
    3 / 28 (10.71%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3

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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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    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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