Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   38147   clinical trials with a EudraCT protocol, of which   6265   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A 16-Week, Randomized, Placebo-Controlled, Double Blind, and Parallel Group Trial to Assess the Anti-Inflammatory Effects of Roflumilast in Chronic Obstructive Pulmonary Disease. The ROBERT Study (Roflumilast Biopsy European Research Trial)

    Summary
    EudraCT number
    2011-000582-13
    Trial protocol
    DE   GB   SE   PL   DK  
    Global end of trial date
    11 Feb 2016

    Results information
    Results version number
    v1(current)
    This version publication date
    08 Feb 2017
    First version publication date
    08 Feb 2017
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    RO-2455-402-RD
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01509677
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    Register Identifier: U1111-1155-8767
    Sponsors
    Sponsor organisation name
    AstraZeneca
    Sponsor organisation address
    1800 Concord Pike, PO Box 15437, Wilmington, United States, DE 19850
    Public contact
    AstraZeneca Clinical Study Information Center, AstraZeneca, 001 18772409479 x, information.center@astrazeneca.com
    Scientific contact
    AstraZeneca Clinical Study Information Center, AstraZeneca, 001 18772409479 x, information.center@astrazeneca.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
    24 Jul 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    10 Feb 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Feb 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To investigate the effect of roflumilast 500 μg tablets once daily versus placebo on inflammation parameters in bronchial biopsy tissue specimen.
    Protection of trial subjects
    SABA or SAMA could be used as rescue medication according to the individual needs of a patient.
    Background therapy
    Therapy consisting of any bronchodilator such as SABA, SAMA, LABA, or LAMA starting at least 6 weeks prior to V0 was allowed. The treatment had to remain stable in the course of the whole study, that is, 6 weeks of single-blind placebo administration (run-in) and 16 weeks of double-blind treatment period.
    Evidence for comparator
    -
    Actual start date of recruitment
    04 Jan 2012
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    1 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Denmark: 8
    Country: Number of subjects enrolled
    Germany: 42
    Country: Number of subjects enrolled
    Poland: 33
    Country: Number of subjects enrolled
    Sweden: 14
    Country: Number of subjects enrolled
    United Kingdom: 61
    Worldwide total number of subjects
    158
    EEA total number of subjects
    158
    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)
    83
    From 65 to 84 years
    75
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    N=281

    Pre-assignment period milestones
    Number of subjects started
    281 [1]
    Number of subjects completed
    158

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    Protocol deviation: 123
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: According to the CSR, 296 subject where screened, of these 15 subjects were re-enrolled in the study. This gives us 281 unique patients.
    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
    Carer, Assessor, Subject, Investigator, Monitor, Data analyst

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    R500
    Arm description
    Roflumilast 500 µg
    Arm type
    Experimental

    Investigational medicinal product name
    Roflumilast
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    500 µg tablet once daily, oral administration

    Arm title
    Placebo
    Arm description
    Placebo
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    tablet, once daily, oral administration

    Number of subjects in period 1
    R500 Placebo
    Started
    79
    79
    Completed
    76
    73
    Not completed
    3
    6
         Adverse event, non-fatal
    3
    3
         Consent withdrawn by subject
    -
    3

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    R500
    Reporting group description
    Roflumilast 500 µg

    Reporting group title
    Placebo
    Reporting group description
    Placebo

    Reporting group values
    R500 Placebo Total
    Number of subjects
    79 79 158
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    37 46 83
        65 years and over
    42 33 75
    Age Continuous |
    Units: Years
        arithmetic mean (standard deviation)
    64 ± 8.23 62.5 ± 8.43 -
    Gender, Male/Female
    Units: Participants
        Female
    19 18 37
        Male
    60 61 121
    Race/Ethnicity, Customized
    Units: Subjects
        Asian
    0 1 1
        Black or African American
    1 0 1
        White
    77 77 154
        Other
    1 1 2
    Age, Customized
    Units: Subjects
        Between 18 and 65 years
    37 46 83
        >=65 years
    42 33 75
    Region of Enrollment
    Units: Subjects
        Europe
    79 79 158

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    R500
    Reporting group description
    Roflumilast 500 µg

    Reporting group title
    Placebo
    Reporting group description
    Placebo

    Primary: Number of CD8+ inflammatory cells in bronchial biopsy tissue.

    Close Top of page
    End point title
    Number of CD8+ inflammatory cells in bronchial biopsy tissue. [1]
    End point description
    End point type
    Primary
    End point timeframe
    16 weeks
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses colected.
    End point values
    R500 Placebo
    Number of subjects analysed
    79
    79
    Units: Cells/mm^2
        arithmetic mean (standard deviation)
    442.4 ± 312.74
    427.1 ± 261.42
    No statistical analyses for this end point

    Primary: Number of CD8+ inflammatory cells in bronchial biopsy tissue

    Close Top of page
    End point title
    Number of CD8+ inflammatory cells in bronchial biopsy tissue
    End point description
    End point type
    Primary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    79
    79
    Units: Cells/mm^2
        arithmetic mean (standard deviation)
    13.4 ± 302.69
    29.4 ± 298.88
    Statistical analysis title
    Number of CD8+ inflammatory cells
    Statistical analysis description
    2-sided test at 5% significant level
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.7922
    Method
    Poisson regression model
    Confidence interval

    Secondary: CD68+ Count in Biopsied Material (submucosa)

    Close Top of page
    End point title
    CD68+ Count in Biopsied Material (submucosa)
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    79
    79
    Units: Cells/mm^2
        arithmetic mean (standard deviation)
    149.1 ± 113.91
    124.4 ± 93.15
    Statistical analysis title
    CD68+ Cell count
    Statistical analysis description
    2-sided, 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.7145
    Method
    Poisson regression model
    Confidence interval

    Secondary: CD68+ Cell Count in Biopsied Material (submucosa): Poisson regression (ratio)

    Close Top of page
    End point title
    CD68+ Cell Count in Biopsied Material (submucosa): Poisson regression (ratio)
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    79
    79
    Units: Cells/mm^2
        number (not applicable)
    126.8
    121.6
    Statistical analysis title
    CD68+ Cell count (ratio)
    Statistical analysis description
    2-sided 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 7136
    Method
    Poisson regression model
    Parameter type
    Risk ratio (RR)
    Point estimate
    1.04
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.83
         upper limit
    1.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.119

    Secondary: Change from V2 to V6 in CD68+ Cell Count in Biopsied Material (submucosa) (ITT)

    Close Top of page
    End point title
    Change from V2 to V6 in CD68+ Cell Count in Biopsied Material (submucosa) (ITT)
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    49
    46
    Units: Cells/mm^2
        least squares mean (standard error)
    6.1 ± 10.99
    -5.3 ± 11.05
    Statistical analysis title
    Change from V2 to V6 in CD68+ Cell count
    Statistical analysis description
    2-sided 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.4606
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    11.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -19.2
         upper limit
    42.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    15.45

    Secondary: CD4+ Cell Counts in biopsied Material (submucosa)

    Close Top of page
    End point title
    CD4+ Cell Counts in biopsied Material (submucosa)
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    79
    79
    Units: Cells/mm^2
        number (not applicable)
    304.6
    255
    Statistical analysis title
    CD4+ Cell Counts in biopsied Material
    Statistical analysis description
    2-sided 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2744
    Method
    Poisson regression model
    Parameter type
    Risk ratio (RR)
    Point estimate
    1.19
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.87
         upper limit
    1.64
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.194

    Secondary: CD45+ Cell Counts in biopsied Material (submucosa)

    Close Top of page
    End point title
    CD45+ Cell Counts in biopsied Material (submucosa)
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    79
    79
    Units: Cells/mm^2
        number (not applicable)
    818.4
    960.3
    Statistical analysis title
    CD45+ Cell counts in biopsied Material
    Statistical analysis description
    2-sided 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1128
    Method
    Poisson regression model
    Parameter type
    Risk ratio (RR)
    Point estimate
    0.85
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.7
         upper limit
    1.04
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.086

    Secondary: Neutrophils Cell Counts in biopsied Material (submucosa)

    Close Top of page
    End point title
    Neutrophils Cell Counts in biopsied Material (submucosa)
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    79
    79
    Units: Cells/mm^2
        number (not applicable)
    118.6
    127.7
    Statistical analysis title
    Nuetrophils cell count in biopsied material
    Statistical analysis description
    2-sided 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.674
    Method
    Poisson regression model
    Parameter type
    Risk ratio (RR)
    Point estimate
    0.93
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.66
         upper limit
    1.31
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.164

    Secondary: CD8+ Cell Count in biopsied material (Bronchial Epithelium)

    Close Top of page
    End point title
    CD8+ Cell Count in biopsied material (Bronchial Epithelium)
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    79
    79
    Units: Cells/mm^2
        number (not applicable)
    422.1
    505.3
    Statistical analysis title
    CD8+ cell count (bronchial epithelium)
    Statistical analysis description
    2-sided 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0677
    Method
    Poisson regression model
    Parameter type
    Risk ratio (RR)
    Point estimate
    0.84
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.69
         upper limit
    1.01
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.082

    Secondary: CD68+ Cell Count in biopsied material (Bronchial Epithelium)

    Close Top of page
    End point title
    CD68+ Cell Count in biopsied material (Bronchial Epithelium)
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    79
    79
    Units: Cells/mm^2
        number (not applicable)
    76.3
    93.1
    Statistical analysis title
    CD68+ cell count (bronchial epithelium)
    Statistical analysis description
    2-sided 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.3566
    Method
    Poisson regression model
    Parameter type
    Risk ratio (RR)
    Point estimate
    0.84
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.54
         upper limit
    1.25
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.177

    Secondary: Change from V1 to V5 in Absolute Cell Count inInduced Sputum (10^6/mL): Between-Treatment Difference (Neutrophils)

    Close Top of page
    End point title
    Change from V1 to V5 in Absolute Cell Count inInduced Sputum (10^6/mL): Between-Treatment Difference (Neutrophils)
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    43
    44
    Units: 10^6/mL
        least squares mean (standard error)
    1.7181 ± 1.64471
    0.0827 ± 1.6122
    Statistical analysis title
    V1 to V5 in Absolute cell count (Neutrophils)
    Statistical analysis description
    2 sided 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    87
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.4794
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    1.6354
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.9429
         upper limit
    6.2137
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.30185

    Secondary: Change from V1 to V5 in Absolute Cell Count inInduced Sputum (10^6/mL): Between-Treatment Difference (Macrophages)

    Close Top of page
    End point title
    Change from V1 to V5 in Absolute Cell Count inInduced Sputum (10^6/mL): Between-Treatment Difference (Macrophages)
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    43
    44
    Units: 10^6/mL
        least squares mean (standard error)
    0.1017 ± 0.23396
    -0.371 ± 0.2297
    Statistical analysis title
    V1 to V5 in Absolute Cell count (Macrophages)
    Statistical analysis description
    2 sided 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    87
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.1541
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.4727
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.181
         upper limit
    1.1264
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.32866

    Secondary: Change from V1 to V5 in Absolute Cell Count inInduced Sputum (10^6/mL): Between-Treatment Difference (Eosinophils)

    Close Top of page
    End point title
    Change from V1 to V5 in Absolute Cell Count inInduced Sputum (10^6/mL): Between-Treatment Difference (Eosinophils)
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    43
    44
    Units: 10^6/mL
        least squares mean (standard error)
    -0.0986 ± 0.02639
    -0.036 ± 0.02585
    Statistical analysis title
    V1 to V5 in Absolute Cell count (Eosinophils)
    Statistical analysis description
    2 sided 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    87
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0927
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.0626
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.1358
         upper limit
    0.0106
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.03681

    Secondary: Change from V1 to V5 in Absolute Cell Count inInduced Sputum (10^6/mL): Between-Treatment Difference (Lymphocytes)

    Close Top of page
    End point title
    Change from V1 to V5 in Absolute Cell Count inInduced Sputum (10^6/mL): Between-Treatment Difference (Lymphocytes)
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    43
    44
    Units: 10^6/mL
        least squares mean (standard error)
    -0.0167 ± 0.01167
    0.006 ± 0.01141
    Statistical analysis title
    V1 to V5 in Absolute Cell count (Lymphocetes)
    Statistical analysis description
    2 sided 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    87
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.5175
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.0107
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.0435
         upper limit
    0.022
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.01647

    Secondary: Change from V1 to V5 in Differential Cell Count in Induced Sputum(10^6/mL) (Neutrophils)

    Close Top of page
    End point title
    Change from V1 to V5 in Differential Cell Count in Induced Sputum(10^6/mL) (Neutrophils)
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    45
    44
    Units: 10^6/mL
        least squares mean (standard error)
    2.527 ± 2.3571
    0.382 ± 2.3535
    Statistical analysis title
    V1 to V5 in Differential Cell count (Neutrophils)
    Statistical analysis description
    2-sided 5 % test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.5205
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    2.146
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.466
         upper limit
    8.757
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.3253

    Secondary: Change from V1 to V5 in Differential Cell Count in Induced Sputum(10^6/mL) (Macrophages)

    Close Top of page
    End point title
    Change from V1 to V5 in Differential Cell Count in Induced Sputum(10^6/mL) (Macrophages)
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    45
    44
    Units: 10^6/mL
        least squares mean (standard error)
    0.315 ± 2.1328
    -0.826 ± 2.1316
    Statistical analysis title
    V1 to V5 in Differential Cell count (Macrophages)
    Statistical analysis description
    2-sided 5 % test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.7052
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    1.141
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.835
         upper limit
    7.117
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.0057

    Secondary: Change from V1 to V5 in Differential Cell Count in Induced Sputum(10^6/mL) (Eosinophils)

    Close Top of page
    End point title
    Change from V1 to V5 in Differential Cell Count in Induced Sputum(10^6/mL) (Eosinophils)
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    45
    44
    Units: 10^6/mL
        least squares mean (standard error)
    -1.826 ± 0.5214
    0.041 ± 0.52
    Statistical analysis title
    V1 to V5 in Differential Cell count (Eosinophils)
    Statistical analysis description
    2-sided 5 % test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0127
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.867
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.324
         upper limit
    -0.409
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.7331

    Secondary: Change from V1 to V5 in Differential Cell Count in Induced Sputum(10^6/mL) (Lymphocytes)

    Close Top of page
    End point title
    Change from V1 to V5 in Differential Cell Count in Induced Sputum(10^6/mL) (Lymphocytes)
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    45
    44
    Units: 10^6/mL
        least squares mean (standard error)
    -0.137 ± 0.1332
    -0.086 ± 1.329
    Statistical analysis title
    V1 to V5 in Differential Cell count (Lymphocytes)
    Statistical analysis description
    2-sided 5 % test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.7862
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.051
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.423
         upper limit
    0.321
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1871

    Secondary: Change from baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of interest (FAS) (alfa- 2-Macroglobulin (µg/mL))

    Close Top of page
    End point title
    Change from baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of interest (FAS) (alfa- 2-Macroglobulin (µg/mL))
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    54
    57
    Units: µg/mL
        least squares mean (standard error)
    -0.32 ± 0.73
    -0.48 ± 0.7
    Statistical analysis title
    Change from Base of conc. of alfa-2-Macroglobulin
    Statistical analysis description
    2-sided 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.8769
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.16
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.84
         upper limit
    2.15
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.005

    Secondary: Change from baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of interest (FAS) (IL-8 (pg/mL))

    Close Top of page
    End point title
    Change from baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of interest (FAS) (IL-8 (pg/mL))
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    54
    56
    Units: pg/mL
        least squares mean (standard error)
    -827.3 ± 1995.79
    -1538.4 ± 1941.08
    Statistical analysis title
    Change from Base of conc. of IL-8
    Statistical analysis description
    2-sided 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.7978
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    711.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4778.3
         upper limit
    6200.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    2768.79

    Secondary: Change from baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of interest (FAS) (MMP type 9 (ng/mL))

    Close Top of page
    End point title
    Change from baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of interest (FAS) (MMP type 9 (ng/mL))
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    55
    57
    Units: ng/mL
        least squares mean (standard error)
    80.1 ± 57.07
    -8.4 ± 55.44
    Statistical analysis title
    Change from Base of conc of MMP type 9
    Statistical analysis description
    2-sided 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2669
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    88.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -68.6
         upper limit
    245.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    79.26

    Secondary: Change from baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of interest (FAS) (MCP-1 (pg/mL))

    Close Top of page
    End point title
    Change from baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of interest (FAS) (MCP-1 (pg/mL))
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    53
    57
    Units: pg/mL
        least squares mean (standard error)
    -95.2 ± 49.23
    -69.3 ± 46.93
    Statistical analysis title
    Change from Base of conc MCP-1
    Statistical analysis description
    2-sided 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.7033
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -25.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -160.3
         upper limit
    108.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    67.78

    Secondary: Change from baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of interest (FAS) (TIMP-1 (ng/mL))

    Close Top of page
    End point title
    Change from baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of interest (FAS) (TIMP-1 (ng/mL))
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    54
    57
    Units: ng/mL
        least squares mean (standard error)
    25.87 ± 13.085
    -1.92 ± 12.551
    Statistical analysis title
    Change from Base of conc of TIMP-1
    Statistical analysis description
    2-sided 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1264
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    27.79
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.97
         upper limit
    63.55
    Variability estimate
    Standard error of the mean
    Dispersion value
    18.039

    Secondary: Change from baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of interest (FAS) (VEGF (pg/mL))

    Close Top of page
    End point title
    Change from baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of interest (FAS) (VEGF (pg/mL))
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    55
    57
    Units: pg/mL
        least squares mean (standard error)
    253.1 ± 89.46
    -43.7 ± 86.84
    Statistical analysis title
    Change from Base of conc. VEGF
    Statistical analysis description
    2-sided 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0185
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    296.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    50.9
         upper limit
    542.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    124.07

    Secondary: Change from baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of interest (FAS) (alfa-2-Macroglobulin (µg/mL))

    Close Top of page
    End point title
    Change from baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of interest (FAS) (alfa-2-Macroglobulin (µg/mL))
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    68
    66
    Units: µg/mL
        least squares mean (standard error)
    -0.05 ± 0.061
    -0.05 ± 0.062
    Statistical analysis title
    Change from Base of conc of alfa-2-Macroglobulin
    Statistical analysis description
    2-sided 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    134
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.9989
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.17
         upper limit
    0.17
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.086

    Secondary: Change from baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of interest (FAS) (IL-8 (pg/mL))

    Close Top of page
    End point title
    Change from baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of interest (FAS) (IL-8 (pg/mL))
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    68
    66
    Units: pg/mL
        least squares mean (standard error)
    -4.48 ± 0.929
    -3.92 ± 0.945
    Statistical analysis title
    Change from Base of conc IL-8
    Statistical analysis description
    2-sided 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    134
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.6701
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.56
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.15
         upper limit
    2.03
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.309

    Secondary: Change from baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of interest (FAS) (MMP type 9 (ng/mL))

    Close Top of page
    End point title
    Change from baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of interest (FAS) (MMP type 9 (ng/mL))
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    68
    66
    Units: ng/mL
        least squares mean (standard error)
    0.8 ± 0.78
    -1 ± 0.79
    Statistical analysis title
    Change from Base of conc. of MMP type 9
    Statistical analysis description
    2-sided 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    134
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1105
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    1.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.4
         upper limit
    3.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.1

    Secondary: Change from baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of interest (FAS) (MCP-1(pg/mL))

    Close Top of page
    End point title
    Change from baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of interest (FAS) (MCP-1(pg/mL))
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    68
    66
    Units: pg/mL
        least squares mean (standard error)
    -24.8 ± 11
    -23.4 ± 11.21
    Statistical analysis title
    Change from Base of conc. of MCP-1
    Statistical analysis description
    2-sided 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    134
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.9261
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -32.4
         upper limit
    29.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    15.62

    Secondary: Change from baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of interest (FAS) (TIMP-1(ng/mL))

    Close Top of page
    End point title
    Change from baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of interest (FAS) (TIMP-1(ng/mL))
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    68
    66
    Units: ng/mL
        least squares mean (standard error)
    2.7 ± 3.19
    -7.5 ± 3.25
    Statistical analysis title
    Change from Base of conc. of TIMP-1
    Statistical analysis description
    2-sided 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    134
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0257
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    10.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.2
         upper limit
    19
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.49

    Secondary: Change from baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of interest (FAS) (VEGF(pg/mL))

    Close Top of page
    End point title
    Change from baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of interest (FAS) (VEGF(pg/mL))
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    68
    66
    Units: pg/mL
        least squares mean (standard error)
    11.3 ± 12.8
    -21.5 ± 13.08
    Statistical analysis title
    Change from Base of conc. of VEGF
    Statistical analysis description
    2-sided 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    134
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0728
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    32.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3
         upper limit
    168.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    18.11

    Secondary: Change from baseline in lung function variables: Between-Treatment Differences (FAS) (FEV1 (L))

    Close Top of page
    End point title
    Change from baseline in lung function variables: Between-Treatment Differences (FAS) (FEV1 (L))
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    77
    77
    Units: Litres
        least squares mean (standard error)
    0.028 ± 0.0212
    -0.035 ± 0.0212
    Statistical analysis title
    Change from base in lung function var (FEV1)
    Statistical analysis description
    2-sided 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    154
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.038
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.063
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.004
         upper limit
    0.122
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.03

    Secondary: Change from baseline in lung function variables: Between-Treatment Differences (FAS) (FVC (L))

    Close Top of page
    End point title
    Change from baseline in lung function variables: Between-Treatment Differences (FAS) (FVC (L))
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    77
    77
    Units: Litres
        least squares mean (standard error)
    0.031 ± 0.0391
    -0.033 ± 0.391
    Statistical analysis title
    Change from base in lung function var: (FVC)
    Statistical analysis description
    2-sided 5% test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    154
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2482
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.064
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.045
         upper limit
    0.173
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0552

    Secondary: Wicoxon Signed-rank test for Change from V2 to V6 in FEV1/FVC: Within Treatment Difference

    Close Top of page
    End point title
    Wicoxon Signed-rank test for Change from V2 to V6 in FEV1/FVC: Within Treatment Difference
    End point description
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    R500 Placebo
    Number of subjects analysed
    77
    77
    Units: percentage
        number (confidence interval 95%)
    0.5 (0 to 1)
    -0.5 (-1 to 0.5)
    Statistical analysis title
    Mann-Whitney U-test V2 to V6 in FEV1/FVC
    Statistical analysis description
    2 sided 5 % test
    Comparison groups
    R500 v Placebo
    Number of subjects included in analysis
    154
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2629
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges-Lehmann point estimate
    Point estimate
    -1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    1

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    24 weeks
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    18.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Placebo

    Reporting group title
    R500
    Reporting group description
    Roflumilast 500 µg

    Serious adverse events
    Placebo R500
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 79 (6.33%)
    8 / 79 (10.13%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Investigations
    Influenza A virus test positive
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 79 (1.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lung adenocarcinoma
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 79 (1.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal cancer
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 79 (1.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Hydrocele
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 79 (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
    COPD
         subjects affected / exposed
    1 / 79 (1.27%)
    3 / 79 (3.80%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 79 (1.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 79 (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
    Incarcerated hernia
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 79 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 79 (1.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Dyspepsia
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 79 (1.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Spermatocele
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 79 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Synovial cyst
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 79 (1.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Diverticulitis
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 79 (1.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 79 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    Placebo R500
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    57 / 79 (72.15%)
    66 / 79 (83.54%)
    Injury, poisoning and procedural complications
    Laceration
         subjects affected / exposed
    2 / 79 (2.53%)
    0 / 79 (0.00%)
         occurrences all number
    2
    0
    Procedural pain
         subjects affected / exposed
    0 / 79 (0.00%)
    3 / 79 (3.80%)
         occurrences all number
    0
    3
    Investigations
    Forced expiratory volume decreased
         subjects affected / exposed
    3 / 79 (3.80%)
    0 / 79 (0.00%)
         occurrences all number
    3
    0
    Weight decreased
         subjects affected / exposed
    2 / 79 (2.53%)
    6 / 79 (7.59%)
         occurrences all number
    2
    6
    White blood cell count increased
         subjects affected / exposed
    0 / 79 (0.00%)
    2 / 79 (2.53%)
         occurrences all number
    0
    2
    Respiratory, thoracic and mediastinal disorders
    Bronchial polyp
         subjects affected / exposed
    2 / 79 (2.53%)
    1 / 79 (1.27%)
         occurrences all number
    2
    1
    COPD
         subjects affected / exposed
    12 / 79 (15.19%)
    9 / 79 (11.39%)
         occurrences all number
    13
    10
    Cough
         subjects affected / exposed
    12 / 79 (15.19%)
    10 / 79 (12.66%)
         occurrences all number
    12
    11
    Dyspnoea
         subjects affected / exposed
    1 / 79 (1.27%)
    3 / 79 (3.80%)
         occurrences all number
    1
    3
    Haemoptysis
         subjects affected / exposed
    0 / 79 (0.00%)
    3 / 79 (3.80%)
         occurrences all number
    0
    4
    Productive cough
         subjects affected / exposed
    2 / 79 (2.53%)
    0 / 79 (0.00%)
         occurrences all number
    3
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 79 (0.00%)
    2 / 79 (2.53%)
         occurrences all number
    0
    2
    Rhinorrhoea
         subjects affected / exposed
    3 / 79 (3.80%)
    1 / 79 (1.27%)
         occurrences all number
    3
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 79 (0.00%)
    3 / 79 (3.80%)
         occurrences all number
    0
    3
    Haedache
         subjects affected / exposed
    3 / 79 (3.80%)
    4 / 79 (5.06%)
         occurrences all number
    3
    4
    Lethargy
         subjects affected / exposed
    0 / 79 (0.00%)
    3 / 79 (3.80%)
         occurrences all number
    0
    4
    Tremor
         subjects affected / exposed
    0 / 79 (0.00%)
    3 / 79 (3.80%)
         occurrences all number
    0
    3
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    3 / 79 (3.80%)
    3 / 79 (3.80%)
         occurrences all number
    3
    3
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    2 / 79 (2.53%)
    7 / 79 (8.86%)
         occurrences all number
    2
    7
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    4 / 79 (5.06%)
    11 / 79 (13.92%)
         occurrences all number
    4
    11
    Dry mouth
         subjects affected / exposed
    3 / 79 (3.80%)
    0 / 79 (0.00%)
         occurrences all number
    3
    0
    Nausea
         subjects affected / exposed
    1 / 79 (1.27%)
    6 / 79 (7.59%)
         occurrences all number
    1
    6
    Vomiting
         subjects affected / exposed
    2 / 79 (2.53%)
    5 / 79 (6.33%)
         occurrences all number
    2
    5
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    2 / 79 (2.53%)
    5 / 79 (6.33%)
         occurrences all number
    2
    5
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 79 (0.00%)
    2 / 79 (2.53%)
         occurrences all number
    0
    2
    Muscle spasms
         subjects affected / exposed
    2 / 79 (2.53%)
    2 / 79 (2.53%)
         occurrences all number
    2
    2
    Myalgia
         subjects affected / exposed
    0 / 79 (0.00%)
    3 / 79 (3.80%)
         occurrences all number
    0
    5
    Pain in extremity
         subjects affected / exposed
    0 / 79 (0.00%)
    2 / 79 (2.53%)
         occurrences all number
    0
    2
    Synovial cyst
         subjects affected / exposed
    0 / 79 (0.00%)
    2 / 79 (2.53%)
         occurrences all number
    0
    2
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 79 (1.27%)
    2 / 79 (2.53%)
         occurrences all number
    1
    2
    Infections and infestations
    Eye infection
         subjects affected / exposed
    0 / 79 (0.00%)
    2 / 79 (2.53%)
         occurrences all number
    0
    2
    Herpes zoster
         subjects affected / exposed
    0 / 79 (0.00%)
    2 / 79 (2.53%)
         occurrences all number
    0
    2
    Influenza
         subjects affected / exposed
    2 / 79 (2.53%)
    0 / 79 (0.00%)
         occurrences all number
    2
    0
    Nasopharyngitis
         subjects affected / exposed
    12 / 79 (15.19%)
    13 / 79 (16.46%)
         occurrences all number
    15
    14
    Rhinitis
         subjects affected / exposed
    3 / 79 (3.80%)
    3 / 79 (3.80%)
         occurrences all number
    3
    3
    Urinary tract infection
         subjects affected / exposed
    0 / 79 (0.00%)
    2 / 79 (2.53%)
         occurrences all number
    0
    2
    Viral infection
         subjects affected / exposed
    2 / 79 (2.53%)
    0 / 79 (0.00%)
         occurrences all number
    2
    0

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    12 Jun 2012
    Incl AM 5
    06 Nov 2012
    9
    30 Nov 2012
    Incl Am 5, 9
    23 May 2013
    Incl Am 5, 9, 10
    06 Oct 2014
    Incl all amendments
    21 May 2015
    Incl. all amendments AM 12

    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
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA